Next Article in Journal
Gender and Race-Based Health Disparities in COVID-19 Outcomes among Hospitalized Patients in the United States: A Retrospective Analysis of a National Sample
Previous Article in Journal
Global Research Trend in Vaccine Design
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Vaccines
Volume 10
Issue 12
10.3390/vaccines10122035
vaccines-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Advances in Next-Generation Coronavirus Vaccines in Response to Future Virus Evolution

by
Lili Li
†,
Yangyang Wei
†,
Han Yang
†,
Junyu Yan
,
Xin Li
,
Ziqian Li
,
Yuxiu Zhao
,
Hongyang Liang
* and
Hui Wang
*
Beijing Institute of Biological Products Company Limited, Beijing 100176, China
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Vaccines 2022, 10(12), 2035; https://doi.org/10.3390/vaccines10122035
Submission received: 9 November 2022 / Revised: 23 November 2022 / Accepted: 25 November 2022 / Published: 29 November 2022
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
Browse Figures
Review Reports Versions Notes

Abstract

:
Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread to more than 230 countries and territories worldwide since its outbreak in late 2019. In less than three years, infection by SARS-CoV-2 has resulted in over 600 million cases of COVID-19 and over 6.4 million deaths. Vaccines have been developed with unimaginable speed, and 11 have already been approved by the World Health Organization and given Emergency Use Listing. The administration of several first-generation SARS-CoV-2 vaccines has successfully decelerated the spread of COVID-19 but not stopped it completely. In the ongoing fight against viruses, genetic mutations frequently occur in the viral genome, resulting in a decrease in vaccine-induced antibody neutralization and widespread breakthrough infection. Facing the evolution and uncertainty of SARS-CoV-2 in the future, and the possibility of the spillover of other coronaviruses to humans, the need for vaccines with a broad spectrum of antiviral variants against multiple coronaviruses is recognized. It is imperative to develop a universal coronavirus or pan-coronavirus vaccine or drug to combat the ongoing COVID-19 pandemic as well as to prevent the next coronavirus pandemic. In this review, in addition to summarizing the protective effect of approved vaccines, we systematically summarize current work on the development of vaccines aimed at suppressing multiple SARS-CoV-2 variants of concern as well as multiple coronaviruses.

1. Introduction

Coronaviruses are a large group of enveloped single-stranded RNA viruses that can infect a variety of vertebrates [1]; the four recognized types are alpha (α), beta (β), gamma (γ), and delta (δ). In the last two decades, three β-coronavirus strains with high pathogenicity and lethality have emerged as a result of zoonotic transmission. These include severe acute respiratory syndrome coronavirus (SARS-CoV-1), which emerged in China in 2002; Middle East respiratory syndrome coronavirus (MERS-CoV), which emerged in Saudi Arabia and South Korea in 2012; and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first identified in Wuhan, China in late 2019 and is the cause of coronavirus disease 2019 (COVID-19) [2,3]. SARS-CoV-2 was declared a pandemic by the World Health Organization (WHO) on 11 March 2020, and it has spread to almost all countries [4]. Currently, 11 COVID-19 vaccines have been assessed to be safe and effective by WHO (Table 1) [5,6,7,8,9,10,11]. As of 12 September 2022, 138 vaccines are being clinically tested [12]. Vaccines developed using different technology platforms have been widely used to immunize populations worldwide since December 2020 [13]. The COVID-19 vaccines are highly protective against severe illness, hospitalization, and death, although the efficacy of these vaccines declines 6 months after full vaccination, and they cannot prevent breakthrough infections [14]. The vaccines appear to be considerably less protective against the Omicron variant, and the development of new antibody therapies has not progressed in line with the rate at which the virus is mutating the neutralizing epitopes [15,16,17]. There is no drug that is completely effective, and symptomatic treatments are widely followed in clinical therapeutics against SARS-CoV-2 [18]. Additional challenges loom for the next phase in building a future-proof and durable immune repertoire to protect against oncoming viral variants.

2. New Situation Caused by SARS-CoV-2 Evolution

SARS-CoV-2 has been constantly mutating over the course of the pandemic for the last three years [19,20,21]. Naturally occurring genetic variation during replication is more frequent in RNA viruses than in DNA viruses, despite the presence of exonucleases [22,23]. In addition, directed mutation pressure exerted by the host antiviral immune defense system accelerates genetic variation [24,25]. During late 2020, the emergence of variants that posed an increased risk to global public health prompted WHO to conduct more detailed characterization of specific variants of interest (VOI) and variants of concern (VOC), to monitor the variations in the virus and release information on virus variations while working with scientists around the world to deal with the change of the virus. All reported VOCs include five mutant strains: alpha (B.1.1.7), beta (B.1.351), gamma (P.1), delta (B.1.617.2), and omicron (B.1.1.529) [26]. Although these VOCs originated in different countries, a common feature among them is the increase in the number of mutation sites, with the virus becoming more transmissible [27,28,29]. Omicron B.1.1.529 was listed as a VOC on 26 November 2021; it has 36 deletions and mutations in the spike protein compared with the wild type. Compared with the mean reproduction number (R0) of the original strain (2.79), the delta variant has an R0 of 5.08 [30] and the omicron variant has an R0 of more than 8 [30]. During 2022 when the omicron variant was widespread, multiple mutations occurred, and multiple branches evolved (Figure 1).
In late 2021, the omicron variant became the predominant epidemic variant. Unlike previous VOCs, the prevalence of omicron caused some changes in the epidemiological parameters of the virus. As shown in Figure 2A, the number of weekly infections sharply increased in early 2022, from 5 million (June 2021 to December 2021) to more than 15 million, indicating that the infection and transmission capacities of the omicron variant are significantly higher than those of the previous VOCs. In contrast, the number of deaths (the orange curve: Figure 2A) was gradually declining during the period when omicron became a major prevalent VOC (December 2021 to January 2022); the death rate from COVID-19 infection dropped from over 15% to less than 5 (Figure 2B). Although vaccination did not alter breakthrough infections, it had a major effect in reducing severe illness and mortality. A pathogenicity study of omicron infection showed that pathogenicity was significantly attenuated in both upper and lower respiratory tracts [31].
Many studies have shown that inactivated vaccine, viral vector vaccine, and mRNA vaccine based on the genome of the original virus strain have shown significantly lower protection efficiency against the omicron variant [32,33]. In comparing the previous VOC with omicron, administering COVID-19 vaccines provided limited protection against SARS-CoV-2 infection but high protection against severe/critical illness and COVID-19-related deaths in all age groups [34,35,36].

3. Next-Generation Vaccine Design against Mutated Viruses

Numerous studies have shown that the mutations in the omicron variant allow it to evade the protection conferred by vaccines and therapeutic antibodies, which is a concern for people worldwide [37,38,39,40,41]. In light of the COVID-19 pandemic and the unpredictable nature of the virus, there is a growing belief that the virus may not be wiped out completely but rather will coexist with humans for a long time [42,43]. In addition to closely monitoring virus transmission and developing therapeutic drugs, a more profound and the most cost-effective, long-term solution is to develop safe and effective next-generation pan-coronavirus vaccines. Available data indicate that the problems with the approved vaccines are the short duration of the high levels of protective antibodies induced and the insufficient cross-protection against mutated viruses [16]. A strategy to overcome the problems is to boost with homologous and heterologous vaccines in order to increase the titer of cross-reactive antibodies and prolong the duration of protection, such as regular annual booster shots of available vaccines, as is practiced for influenza [44,45]. Another strategy is to include more key epitopes of SARS-CoV-2 or even epitopes of other coronaviruses in the next-generation vaccine design in order to increase the chance of generating more cross-protective antibodies to deal with new mutations of the virus. Furthermore, some studies have used approved vaccine (such as other vaccine strains) as delivery vectors to exert their strong immune activation to increase vaccine immunogenicity. The persistent expression of coronavirus antigens by infection with a delivery vector has also been tested. Moreover, several technologies, including bioinformatic computing and prediction functions [46,47], reverse vaccinology and machine learning [48,49], as well as nanoparticle vectors, viral vectors other than adenoviruses, and chimeric spike mRNA vaccines, have been used, with some positive results. The following sections provide a detailed review of these next-generation coronavirus vaccine development strategies (Table 1 and Figure 3).

4. Strategy One: Booster Immunization with Approved Vaccines

Using an approved vaccine as a booster is certainly a quick and cost-effective option to deal with the mutation of novel coronavirus, although data from multiple clinical trials have shown that the titers of neutralizing antibodies decrease 6 months after immunization with any of the approved SARS-CoV-2 vaccines [33,50,51,52,53]. Results of booster doses 3 and 4 using homologous or heterologous approved vaccines have shown that 2 doses of primary immunization provided limited protection, and the third booster, whether homologous or heterologous, could effectively increase the levels of neutralizing antibodies against the omicron strain, but it decreased significantly after 10 weeks [32,54,55]. The data suggest that booster with a heterologous vaccine may be better than a homologous vaccine [56]. The fourth booster did not significantly prolong the duration of vaccine efficacy compared with the third booster, except for slightly increasing the antibody levels [57]. In addition, vaccines with omicron antigen, which work on the same platform as the approved vaccine, are also being tested in clinical trials [58]. To maintain protection against omicron, regulatory agencies have approved a third dose for healthy vaccinees who are at a risk of the clinical consequences of the postvaccination drop in immunity [59]. There is no doubt that booster immunization with approved vaccines can provide protection against new mutated viruses for a relatively limited time.

5. Strategy Two: Vaccines with More Complex Sources of Spike Protein RBD

SARS-CoV-2 relies on its obligate receptor, angiotensin-converting enzyme 2 (ACE2), to enter cells [60,61,62].The spike protein is a trimeric glycoprotein that comprises two domains: the S1 domain, which contains the RBD, and the S2 domain, which is responsible for membrane fusion [63,64,65,66,67]. The spike protein RBD has become a prime focus in the research and development of pan-coronaviruses because it is the main receptor recognition site, the binding site for neutralizing antibodies, and the site where mutations occur most frequently and gradually increase with virus evolution [68,69,70,71,72,73,74]. The expressed soluble spike protein is the main antigen in all approved vaccines, except inactivated vaccines [9,75,76]. However, previous studies have shown that particle antigens are more effective than free antigens. The repetitive array of the particle surface component allows for robust B cell activation that facilitates memory B cell expansion and the generation of long-lived plasma cells [77,78]. Based on this principle, self-assembling nanoparticles are being used in vaccine research because they provide a robust platform to investigate the concept of particulate vaccines such as virus-like particles (VLPs). Furthermore, self-assembling nanoparticles can improve antigen structure and stability, as well as vaccine-targeted delivery and immunogenicity, all with a good safety profile [79]. Ferritin is a protein that naturally forms nanoparticles composed of 24 identical polypeptides [80,81,82]. Genes encoding immunogenic substances are inserted at the interface of adjacent subunits enabling spontaneous assembly and the generation of eight trimeric viral spikes on the nanoparticle surface [83]. The most advanced ferritin nanoparticle SARS-CoV-2 vaccine, S-trimer-ferritin nanoparticles (SpFN), is in phase I clinical trials conducted by the U.S. Army Medical Research and Development Command (NCT04784767). Preclinical studies demonstrated that SpFN combined with ALFQ, a liposomal adjuvant, can induce potent S-binding and ACE2 inhibiting neutralizing antibody; binding titers and pseudovirus neutralization titers were stably maintained for more than 10 weeks after the final immunization in mice [84]. In another research study, SpFN protected hamsters against alpha and beta coronavirus variants [85]. In nonhuman primate experiments, the vaccine generated more potent SARS-CoV-2-specific B- and T-cell responses than a soluble antigen vaccine, and it protected Chinese-origin rhesus macaques in high-dose virus challenge experiments. SpFN elicited serum virus-neutralizing activity that was either higher than or equivalent to that of the wild-type virus against four major VOCs (B.1.1.7, B.1.351, P.1, and B.1.617.2) in an authentic virus neutralization assay [86].
In the face of coronavirus spillover from animals to humans and unpredictable changes in the virus, mosaic RBD nanoparticles are being used in vaccine research. Cohen et al. constructed several nanoparticles (mosaic-4a, mosaic-4b, mosaic-8, and homotyic SARS-2) that simultaneously displayed RBDs from human and animal coronaviruses [87]. Mice experiments showed that the mosaic RBD nanoparticle vaccine produced neutralizing antibodies and cross protection against multiple coronaviruses, such as bat WIV1 and SHC014 strains, and the antibody level was equal to or greater than that of the single RBD nanoparticle [88]. In a further study, when mosaic-8 nanoparticles were used to immunize mice and nonhuman primates, the animals were protected against SARS-CoV and SARS-CoV-2, including Omicron [89].
In addition to recombinant nanoparticle vaccines, mixing mRNA vaccines with different virus variants Spike proteins are also being developed, and these bivalent mRNA vaccine include a component of the original virus strain to provide broad protection against COVID-19 and a component of the omicron variant to provide better protection against COVID-19 caused by the omicron variant. [90]. In addition, chimeric spike mRNA vaccines were used in one study; these are LNP vaccines that are consistent with approved mRNA vaccines, except that these vaccines express chimeric spikes that contain admixtures of different RBD from SARS-CoV, SARS-CoV-2, SARS-CoV-2 B.1.351, and bat CoV (Bt-CoV) RsSHC014;d a heterologous Bt-CoV WIV-1, N-terminal domain; and S2 modular domains from zoonotic, epidemic, and pandemic coronaviruses. In vivo, the vaccine induced neutralizing antibodies comparable with that of a monovalent vaccine, and old mice were completely protected from bat-derived BT-CoV RsSHC014 and SARS-CoV-2. An advantage of the chimeric spike vaccines is the clear breadth of protection against multiclade sarbecoviruses (SARS-CoV, Bt-CoV RsSHC014, Bt-CoV WIV-1) and SARS-CoV-2 variants (B.1.351) compared with that of monovalent SARS-CoV-2 vaccines [91].
Recombinant nanoparticle vaccines and chimeric spike mRNA vaccines allow for a denser concentration of antigen material and can carry multiple coronavirus antigens, providing additional opportunities for cross protection against mutations of SARS-CoV-2 and unpredictable coronavirus spillovers in the future. We also know that too many antigenic substances not associated with epidemic infections are added to vaccines, which are not recommended by regulators. Perhaps the major challenge for such a vaccine is to predict mutations in the virus, as with influenza, before developing and producing a vaccine and conducting more experiments on safety and efficacy.

6. Strategy Three: Live Attenuated Viral Vaccine Delivered SARS-CoV-2 Antigen

Attenuated vaccines are widely used against various infectious diseases such as smallpox [92,93], Varicella [94,95], Japanese encephalitis [96,97], and yellow fever [98,99]. This type of vaccine is highly immunogenic [100,101], safe based on its history of use [102,103]. Live attenuated vaccine viruses are used for the delivery of antigenic substances and are also widely researched for the treatment of tumors and other diseases [104,105,106,107]. Using this principle, an antigen of SARS-CoV-2 or other coronaviruses is inserted into the attenuated viral genome providing another technology platform for pan-coronavirus vaccine development.
YF17D is a small positive-sense single-stranded RNA live-attenuated virus vaccine for yellow fever virus (YFV) that tolerates some insertion of foreign antigens in the viral polyprotein [108]. A single-dose YF17D vaccination can induce lifelong protective immunity against YFV, and it is well- tolerated in humans, with highly rare adverse events [109,110]. In recent years, YF17D has been used in some vaccine research as an alternative viral vector vaccine platform [111,112,113,114]. Oreshkova et al. [115] established a live attenuated vaccine using YF17D as the delivery vector that comprised a spike protein of three different beta-coronaviruses: MERS-CoV, SARS-CoV, and MHV replaced prM and E of YF17D. The vaccine induced the production of corresponding antibodies on day 42 after booster vaccination. Sanchez-Felipe et al. [116] found that a single dose of YF17D-VECtored SARS-CoV-2 vaccine had a good safety profile in hamsters and nonhuman primates, and it could protect animals from viral attack.
Modified vaccinia Ankara (MVA) is another vaccine candidate for SARS-CoV-2 [117] that induces strong, broad, and polyfunctional SARS-CoV-2 S-specific T-cell immunity and high level B-cell immunity with good safety in mice and hamsters [117,118,119,120]. A recombinant MVA expressing full-length SARS-CoV-2 spike (S) protein named MVA-SARS-2-S was developed by Universitatsklinikum Hamburg-Eppendorf in Germany and has completed Phase I clinical trials (NCT04569383). Preclinical test results confirmed that poxvirus MVA has strong immunogenicity, and S protein can be expressed at a high level in animals to induce strong humoral and cellular immune responses. Vaccines stimulate the production of neutralizing antibodies and protect animals from viruses in protective challenge tests [121]. In addition, Flavia Chiuppesi’s team developed vaccines carrying co-expressing SARS-CoV-2 spike and nucleocapsid antigens using MVA viruses [117].
Live attenuated measles virus (MeV) vaccine has been one of the safest and most efficient human vaccines and has been used in children since the 1960s [122,123]. A measles virus (rMeV) vaccine strain as the backbone expressing various forms of the SARS-CoV-2 spike protein and RBD has been used in animal experiments and was demonstrated to induce high levels of antibodies and a strong Th1-biased T-cell response in vivo, while protecting animals against SARS-CoV-2 infection [124].
In addition to the live attenuated virus, Adeno-associated viruses are commonly used as viral vectors for gene therapy characterized by low immunogenicity and can continuously express the delivered gene after infection [125,126]; they have also been used in a novel coronavirus vaccine. Previous studies have also confirmed that AAV vector vaccines have a good safety profile and induce durable and effective humoral and cellular immunity in mice and nonhuman primates [127,128,129]. In a previous study, the S protein-encoding gene of the original SARS-CoV-2 strain was integrated into AAVrh32.33; the neutralizing antibody levels decreased in treated mice for up to a year. The treatment also induced a durable cellular immune response and provided complete protection against SARS-CoV-2 challenge in cynomolgus monkeys [130]. In another study, AAV6 virus with the spike protein-encoding gene of the original strain was compared with an approved inactivated vaccine in animals and showed that a single dose produced a higher titer and longer lasting IgG antibody [131].
The live virus vector vaccine takes advantage of the characteristics of the virus vector to induce not only a high humoral immune response but also a cellular immune response, which can prolong the protective effect of the vaccine in response to the mutation of the coronavirus.

7. Strategy Four: Subunit Vaccines with T-Cell Epitopes

In classical immunology, serum antibody output would be attenuated in the absence of sustained antigen stimulation, but B and T memory cells would be primed for a rapid, protective response upon repeated antigen encounters [132]. Preclinical studies of SARS-CoV have shown a protective role of T cells in the host defense [133]. Together, the induction of a T-cell immune response and the generation of memory T and B lymphocyte immunity have become an important focus of vaccine design against SARS-CoV-2 mutations [134,135,136].
A recombinant subunit vaccine, UB-612, has been developed by expressing the spike 1 (S1)-RBD fused with a single-chain Fc protein (S1-RBD-sFc), 5 Th cell, and CTL epitope peptides from the nucleocapsid (N), membrane (M), and S2 proteins of sarbecoviruses; and an extrinsic HLA class II epitope (UBITh1a) modified from a measles virus fusion (MVF) protein that would serve as a catalyst for T-cell activation [137]. The virus was used in a clinical trial of a multitarget long-acting vaccine against multiple SARS-CoV-2 variants conducted by Chang Yi Wang et al. in Taiwan, China. In completed clinical trials (ClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742), the vaccine had a favorable safety profile both as a primary and as a third-dose booster. Compared with a panel of human convalescent sera (HCS) collected approximately 1 month after COVID-19 onset in hospitalized cases, the post-booster neutralizing antibody levels (GMFIs) were about 40-fold higher. The most striking findings were a long half-life of 187 days for the neutralizing antibody response, a sustained T-cell response, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the delta and omicron VOCs [138].
Subunit vaccines with conserved T cell epitopes may cause the body to generate cellular immune response to assist the production of antibodies which are high titer and durable.

8. Strategy Five: More Cutting-Edge Vaccine Design Using AI Technology

In addition to clinical studies for SARS-CoV-2, preclinical research has been devoted to the search for T and B cell epitopes in the coronavirus. Through phylogenetic and sequence ratio analyses of coronaviruses, Li et al. [139] investigated the conserved epitopes found in all known human coronaviruses (HCoVs). They then developed a novel antigen based on a genetic algorithm using a mosaic strategy and a broad coverage of CTL epitopes of known HCoVs [139]. Swayam Prakash’s team compared the SARS-CoV-2-Wuhan-Hu-1 (MN908947.3) protein sequence with SARS-CoV- and MERS-CoV-specific protein sequences obtained from human, bat, pangolin, civet, and camel. A total of 15 B cell epitopes, 27 potential human CD8+ T cell epitopes, and 16 potential CD4+ T cell epitopes were highly conserved among 6 strains of coronaviruses previously reported to infect humans. In addition, over 81,000 strains of SARS-CoV-2 that currently circulate in 190 countries on 6 continents were predicted using immune-informatics and sequence alignment. Mice immunized with a mixture of peptides and adjuvants produced IgG against a variety of viruses, some of which were specific for the epitope peptide [140]. Moreover, Ong et al. [48] applied reverse vaccinology tools developed using machine learning to predict COVID-19 vaccine candidates. They proposed that an Sp/Nsp cocktail vaccine containing structural protein and nonstructural protein would stimulate effective complementary immune responses.
AI computing can obtain the genetic information of coronavirus from various sources through big data analysis and predict the evolutionary trend of the virus, which is likely to be an important aid in the design of future vaccines.

9. Conclusions

During the three years of the coronavirus epidemic, viruses evolve as they spread. Several data sources have confirmed that infection with the omicron variant reduces the effectiveness of approved vaccines and the neutralizing power of antibodies. It is not impossible to develop new variant strain vaccines to catch up with virus mutation, but from a global vaccine equity perspective, such an effort will not meet the global demand. It has been confirmed that SARS-1, MARS, and SARS-2 are caused by the spillover of animal viruses. For the unknown virus infection in the future, scientists from different countries are using different strategies to carry out research work.
Because of the prevalence of the virus and the danger of the early virus, many countries around the world have developed the COVID-19 vaccine virus at the fastest speed and in the shortest time, which has been approved for use by WHO. Up to now, more than 68.4% of the world’s population has received at least one dose of COVID-19 vaccine, which also means that the next generation of vaccine is closer to the booster vaccine. The booster immunization of vaccine can provide stronger immune protection in a shorter time. Clinical trials also confirmed that heterologous immunization can produce higher neutralizing antibody titer, although the neutralizing antibody level will decrease with the variation of the virus as a whole [141]. The use of heterologous vaccines consistent with antigenic substances and epidemic strains for strengthening may provide better protection for high-risk people.
In the race against viral mutations, more persistent and high-level humoral immune responses against the spike protein and RBD, stronger vaccine immunogenicity, broader pan-coronavirus cross protection, and greater T-cell immune responses have become the consensus for the development of next-generation coronavirus vaccines.
Research on the next-generation vaccine is in progress, and some positive results have been obtained. Future studies should focus on the following aspects: the immune mechanism and protective effect of the vaccine and whether the vaccine can have the expected effect and good safety. The use of new technologies has led to more ideas for vaccine development, but it will require time to prove whether such vaccines are safe and effective. In addition, there are still many unknowns to be explored in the immunological study of coronavirus infection. Immune imprinting caused by vaccination and earlier VOC infection vary in different individuals, and immune responses to new variants of the virus and next-generation vaccines are unknown. Although some vaccines against the mutant strains have already been tested in clinical trials and safety data have been obtained, scientists around the world still need to explore and study the unpredictable evolution of the virus in the future.

Author Contributions

Conceptualization, L.L.; Writing—Original Draft Preparation, L.L., Y.W. and H.Y. Validation, J.Y., X.L., Z.L., Y.Z., H.L. and H.W. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Howley, P.M.; Knipe, D.M.; Whelan, S. Fields Virology: Emerging Viruses, 7th ed.; Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2020; ISBN 1975112547/978-1975112547. [Google Scholar]
  2. Zhu, Z.; Lian, X.; Su, X.; Wu, W.; Marraro, G.A.; Zeng, Y. From SARS and MERS to COVID-19: A brief summary and comparison of severe acute respiratory infections caused by three highly pathogenic human coronaviruses. Respir. Res. 2020, 21, 224. [Google Scholar] [CrossRef] [PubMed]
  3. To, K.K.; Sridhar, S.; Chiu, K.H.; Hung, D.L.; Li, X.; Hung, I.F.; Tam, A.R.; Chung, T.W.; Chan, J.F.; Zhang, A.J.; et al. Lessons learned 1 year after SARS-CoV-2 emergence leading to COVID-19 pandemic. Emerg. Microbes Infect. 2021, 10, 507–535. [Google Scholar] [CrossRef] [PubMed]
  4. WHO. Virtual Press Conference on COVID-19. 2020. Available online: https://www.who.int/docs/default-source/coronaviruse/transcripts/who-audio-emergencies-coronavirus-press-conference-full-and-final-11mar2020.pdf?sfvrsn=cb432bb3_2 (accessed on 26 October 2022).
  5. Ella, R.; Reddy, S.; Blackwelder, W.; Potdar, V.; Yadav, P.; Sarangi, V.; Aileni, V.K.; Kanungo, S.; Rai, S.; Reddy, P.; et al. Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): Interim results of a randomised, double-blind, controlled, phase 3 trial. Lancet 2021, 398, 2173–2184. [Google Scholar] [CrossRef] [PubMed]
  6. Baden, L.R.; El Sahly, H.M.; Essink, B.; Kotloff, K.; Frey, S.; Novak, R.; Diemert, D.; Spector, S.A.; Rouphael, N.; Creech, C.B.; et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N. Engl. J. Med. 2021, 384, 403–416. [Google Scholar] [CrossRef] [PubMed]
  7. Polack, F.P.; Thomas, S.J.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Perez, J.L.; Pérez Marc, G.; Moreira, E.D.; Zerbini, C.; et al. Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine. N. Engl. J. Med. 2020, 383, 2603–2615. [Google Scholar] [CrossRef]
  8. Voysey, M.; Costa Clemens, S.A.; Madhi, S.A.; Weckx, L.Y.; Folegatti, P.M.; Aley, P.K.; Angus, B.; Baillie, V.L.; Barnabas, S.L.; Bhorat, Q.E.; et al. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: A pooled analysis of four randomised trials. Lancet 2021, 397, 881–891. [Google Scholar] [CrossRef]
  9. Sadoff, J.; Gray, G.; Vandebosch, A.; Cárdenas, V.; Shukarev, G.; Grinsztejn, B.; Goepfert, P.A.; Truyers, C.; Fennema, H.; Spiessens, B.; et al. Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against COVID-19. N. Engl. J. Med. 2021, 384, 2187–2201. [Google Scholar] [CrossRef] [PubMed]
  10. Heath, P.T.; Galiza, E.P.; Baxter, D.N.; Boffito, M.; Browne, D.; Burns, F.; Chadwick, D.R.; Clark, R.; Cosgrove, C.; Galloway, J.; et al. Safety and Efficacy of NVX-CoV2373 COVID-19 Vaccine. N. Engl. J. Med. 2021, 385, 1172–1183. [Google Scholar] [CrossRef] [PubMed]
  11. WHO. Coronavirus Disease (COVID-19): Vaccines. 2022. Available online: https://www.who.int/news-room/questions-and-answers/item/coronavirus-disease-(covid-19)-vaccines (accessed on 30 October 2022).
  12. COVID-19 Vaccine Tacker. Available online: https://vac-lshtmshinyappsio/ncov_vaccine_landscape/ (accessed on 30 October 2022).
  13. Ourworldindata. Coronavirus (COVID-19) Vaccinations. 2022. Available online: https://ourworldindata.org/covid-vaccinations (accessed on 30 October 2022).
  14. Feikin, D.R.; Higdon, M.M.; Abu-Raddad, L.J.; Andrews, N.; Araos, R.; Goldberg, Y.; Groome, M.J.; Huppert, A.; O’Brien, K.L.; Smith, P.G.; et al. Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: Results of a systematic review and meta-regression. Lancet 2022, 399, 924–944. [Google Scholar] [CrossRef]
  15. Wang, X.; Zhao, X.; Song, J.; Wu, J.; Zhu, Y.; Li, M.; Cui, Y.; Chen, Y.; Yang, L.; Liu, J.; et al. Homologous or heterologous booster of inactivated vaccine reduces SARS-CoV-2 Omicron variant escape from neutralizing antibodies. Emerg. Microbes Infect. 2022, 11, 477–481. [Google Scholar] [CrossRef]
  16. Ai, J.; Zhang, H.; Zhang, Y.; Lin, K.; Zhang, Y.; Wu, J.; Wan, Y.; Huang, Y.; Song, J.; Fu, Z.; et al. Omicron variant showed lower neutralizing sensitivity than other SARS-CoV-2 variants to immune sera elicited by vaccines after boost. Emerg. Microbes Infect. 2022, 11, 337–343. [Google Scholar] [CrossRef] [PubMed]
  17. Lyke, K.E.; Atmar, R.L.; Islas, C.D.; Posavad, C.M.; Szydlo, D.; Paul Chourdhury, R.; Deming, M.E.; Eaton, A.; Jackson, L.A.; Branche, A.R.; et al. Rapid decline in vaccine-boosted neutralizing antibodies against SARS-CoV-2 Omicron variant. Cell Rep. Med. 2022, 3, 100679. [Google Scholar] [CrossRef] [PubMed]
  18. Li, G.; De Clercq, E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV). Nature reviews Drug Discov. 2020, 19, 149–150. [Google Scholar] [CrossRef] [Green Version]
  19. Hirabara, S.M.; Serdan, T.D.A.; Gorjao, R.; Masi, L.N.; Pithon-Curi, T.C.; Covas, D.T.; Curi, R.; Durigon, E.L. SARS-CoV-2 Variants: Differences and Potential of Immune Evasion. Front. Cell. Infect. Microbiol. 2021, 11, 781429. [Google Scholar] [CrossRef]
  20. Kumar, S.; Thambiraja, T.S.; Karuppanan, K.; Subramaniam, G. Omicron and Delta variant of SARS-CoV-2: A comparative computational study of spike protein. J. Med. Virol. 2022, 94, 1641–1649. [Google Scholar] [CrossRef]
  21. Papanikolaou, V.; Chrysovergis, A.; Ragos, V.; Tsiambas, E.; Katsinis, S.; Manoli, A.; Papouliakos, S.; Roukas, D.; Mastronikolis, S.; Peschos, D.; et al. From delta to Omicron: S1-RBD/S2 mutation/deletion equilibrium in SARS-CoV-2 defined variants. Gene 2022, 814, 146134. [Google Scholar] [CrossRef]
  22. Denison, M.R.; Graham, R.L.; Donaldson, E.F.; Eckerle, L.D.; Baric, R.S. Coronaviruses: An RNA proofreading machine regulates replication fidelity and diversity. RNA Biol. 2011, 8, 270–279. [Google Scholar] [CrossRef] [Green Version]
  23. Lauring, A.S.; Hodcroft, E.B. Genetic Variants of SARS-CoV-2-What Do They Mean? JAMA 2021, 325, 529–531. [Google Scholar] [CrossRef]
  24. Mourier, T.; Sadykov, M.; Carr, M.J.; Gonzalez, G.; Hall, W.W.; Pain, A. Host-directed editing of the SARS-CoV-2 genome. Biochem. Biophys. Res. Commun. 2021, 538, 35–39. [Google Scholar] [CrossRef]
  25. Wang, R.; Hozumi, Y.; Zheng, Y.H.; Yin, C.; Wei, G.W. Host Immune Response Driving SARS-CoV-2 Evolution. Viruses 2020, 12, 1095. [Google Scholar] [CrossRef]
  26. Aleem, A.; Akbar Samad, A.B.; Slenker, A.K. Emerging Variants of SARS-CoV-2 And Novel Therapeutics Against Coronavirus (COVID-19); StatPearls Publishing: Treasure Island, FL, USA, 2022. [Google Scholar]
  27. Farinholt, T.; Doddapaneni, H.; Qin, X.; Menon, V.; Meng, Q.; Metcalf, G.; Chao, H.; Gingras, M.C.; Avadhanula, V.; Farinholt, P.; et al. Transmission event of SARS-CoV-2 delta variant reveals multiple vaccine breakthrough infections. BMC Med. 2021, 19, 255. [Google Scholar] [CrossRef] [PubMed]
  28. Brown, C.M.; Vostok, J.; Johnson, H.; Burns, M.; Gharpure, R.; Sami, S.; Sabo, R.T.; Hall, N.; Foreman, A.; Schubert, P.L.; et al. Outbreak of SARS-CoV-2 Infections, Including COVID-19 Vaccine Breakthrough Infections, Associated with Large Public Gatherings—Barnstable County, Massachusetts, July 2021. MMWR Morb. Mortal. Wkly. Rep. 2021, 70, 1059–1062. [Google Scholar] [CrossRef] [PubMed]
  29. Mannar, D.; Saville, J.W.; Zhu, X.; Srivastava, S.S.; Berezuk, A.M.; Tuttle, K.S.; Marquez, A.C.; Sekirov, I.; Subramaniam, S. SARS-CoV-2 Omicron variant: Antibody evasion and cryo-EM structure of spike protein-ACE2 complex. Science 2022, 375, 760–764. [Google Scholar] [CrossRef] [PubMed]
  30. Liu, Y.; Rocklöv, J. The reproductive number of the Delta variant of SARS-CoV-2 is far higher compared to the ancestral SARS-CoV-2 virus. J. Travel Med. 2021, 28, taab124. [Google Scholar] [CrossRef] [PubMed]
  31. Shuai, H.; Chan, J.F.; Hu, B.; Chai, Y.; Yuen, T.T.; Yin, F.; Huang, X.; Yoon, C.; Hu, J.C.; Liu, H.; et al. Attenuated replication and pathogenicity of SARS-CoV-2 B.1.1.529 Omicron. Nature 2022, 603, 693–699. [Google Scholar] [CrossRef] [PubMed]
  32. Pérez-Then, E.; Lucas, C.; Monteiro, V.S.; Miric, M.; Brache, V.; Cochon, L.; Vogels, C.B.F.; Malik, A.A.; De la Cruz, E.; Jorge, A.; et al. Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination. Nat. Med. 2022, 28, 481–485. [Google Scholar] [CrossRef]
  33. Edara, V.V.; Manning, K.E.; Ellis, M.; Lai, L.; Moore, K.M.; Foster, S.L.; Floyd, K.; Davis-Gardner, M.E.; Mantus, G.; Nyhoff, L.E.; et al. mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 omicron variant. Cell Rep. Med. 2022, 3, 100529. [Google Scholar] [CrossRef]
  34. Huang, Z.; Xu, S.; Liu, J.; Wu, L.; Qiu, J.; Wang, N.; Ren, J.; Li, Z.; Guo, X.; Tao, F.; et al. Effectiveness of inactivated and Ad5-nCoV COVID-19 vaccines against SARS-CoV-2 Omicron BA. 2 variant infection, severe illness, and death. BMC Med. 2022, 20, 400. [Google Scholar] [CrossRef]
  35. Andrews, N.; Stowe, J.; Kirsebom, F.; Toffa, S.; Rickeard, T.; Gallagher, E.; Gower, C.; Kall, M.; Groves, N.; O’Connell, A.M.; et al. COVID-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant. N. Engl. J. Med. 2022, 386, 1532–1546. [Google Scholar] [CrossRef]
  36. Zeng, B.; Gao, L.; Zhou, Q.; Yu, K.; Sun, F. Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern: A systematic review and meta-analysis. BMC Med. 2022, 20, 200. [Google Scholar] [CrossRef]
  37. Collie, S.; Champion, J.; Moultrie, H.; Bekker, L.G.; Gray, G. Effectiveness of BNT162b2 Vaccine against Omicron Variant in South Africa. N. Engl. J. Med. 2022, 386, 494–496. [Google Scholar] [CrossRef] [PubMed]
  38. Tuekprakhon, A.; Nutalai, R.; Dijokaite-Guraliuc, A.; Zhou, D.; Ginn, H.M.; Selvaraj, M.; Liu, C.; Mentzer, A.J.; Supasa, P.; Duyvesteyn, H.M.E.; et al. Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum. Cell 2022, 185, 2422–2433.e13. [Google Scholar] [CrossRef] [PubMed]
  39. Kuhlmann, C.; Mayer, C.K.; Claassen, M.; Maponga, T.; Burgers, W.A.; Keeton, R.; Riou, C.; Sutherland, A.D.; Suliman, T.; Shaw, M.L.; et al. Breakthrough infections with SARS-CoV-2 omicron despite mRNA vaccine booster dose. Lancet 2022, 399, 625–626. [Google Scholar] [CrossRef] [PubMed]
  40. Carreño, J.M.; Alshammary, H.; Tcheou, J.; Singh, G.; Raskin, A.J.; Kawabata, H.; Sominsky, L.A.; Clark, J.J.; Adelsberg, D.C.; Bielak, D.A.; et al. Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron. Nature 2022, 602, 682–688. [Google Scholar] [CrossRef] [PubMed]
  41. Planas, D.; Saunders, N.; Maes, P.; Guivel-Benhassine, F.; Planchais, C.; Buchrieser, J.; Bolland, W.H.; Porrot, F.; Staropoli, I.; Lemoine, F.; et al. Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Nature 2022, 602, 671–675. [Google Scholar] [CrossRef]
  42. Looi, M.K. The BMJ Interview: WHO chief scientist optimistic for a pan-coronavirus vaccine in two years. BMJ 2022, 377, o1003. [Google Scholar] [CrossRef] [PubMed]
  43. Lavine, J.S.; Bjornstad, O.N.; Antia, R. Immunological characteristics govern the transition of COVID-19 to endemicity. Science 2021, 371, 741–745. [Google Scholar] [CrossRef]
  44. Luo, R.; Delaunay-Moisan, A.; Timmis, K.; Danchin, A. SARS-CoV-2 biology and variants: Anticipation of viral evolution and what needs to be done. Environ. Microbiol. 2021, 23, 2339–2363. [Google Scholar] [CrossRef]
  45. Sandor, A.M.; Sturdivant, M.S.; Ting, J.P.Y. Influenza Virus and SARS-CoV-2 Vaccines. J. Immunol. 2021, 206, 2509–2520. [Google Scholar] [CrossRef]
  46. Martin, W.R.; Cheng, F. A rational design of a multi-epitope vaccine against SARS-CoV-2 which accounts for the glycan shield of the spike glycoprotein. J. Biomol. Struct. Dyn. 2022, 40, 7099–7113. [Google Scholar] [CrossRef]
  47. Kibria, K.M.K.; Faruque, M.O.; Islam, M.S.B.; Ullah, H.; Mahmud, S.; Miah, M.; Saleh, A.A. A conserved subunit vaccine designed against SARS-CoV-2 variants showed evidence in neutralizing the virus. Appl. Microbiol. Biotechnol. 2022, 106, 4091–4114. [Google Scholar] [CrossRef] [PubMed]
  48. Ong, E.; Wong, M.U.; Huffman, A.; He, Y. COVID-19 Coronavirus Vaccine Design Using Reverse Vaccinology and Machine Learning. Front. Immunol. 2020, 11, 1581. [Google Scholar] [CrossRef] [PubMed]
  49. Shi, J.; Zhang, J.; Li, S.; Sun, J.; Teng, Y.; Wu, M.; Li, J.; Li, Y.; Hu, N.; Wang, H.; et al. Epitope-Based Vaccine Target Screening against Highly Pathogenic MERS-CoV: An In Silico Approach Applied to Emerging Infectious Diseases. PLoS ONE 2015, 10, e0144475. [Google Scholar] [CrossRef] [Green Version]
  50. Cele, S.; Jackson, L.; Khoury, D.S.; Khan, K.; Moyo-Gwete, T.; Tegally, H.; San, J.E.; Cromer, D.; Scheepers, C.; Amoako, D.G.; et al. Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization. Nature 2022, 602, 654–656. [Google Scholar] [CrossRef]
  51. Muik, A.; Lui, B.G.; Wallisch, A.K.; Bacher, M.; Mühl, J.; Reinholz, J.; Ozhelvaci, O.; Beckmann, N.; Güimil Garcia, R.C.; Poran, A.; et al. Neutralization of SARS-CoV-2 Omicron by BNT162b2 mRNA vaccine-elicited human sera. Science 2022, 375, 678–680. [Google Scholar] [CrossRef] [PubMed]
  52. Lu, L.; Mok, B.W.Y.; Chen, L.L.; Chan, J.M.C.; Tsang, O.T.Y.; Lam, B.H.S.; Chuang, V.W.M.; Chu, A.W.H.; Chan, W.M.; Ip, J.D.; et al. Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant by Sera from BNT162b2 or CoronaVac Vaccine Recipients. Clin. Infect. Dis. 2022, 75, e822–e826. [Google Scholar] [CrossRef]
  53. Edridge, A.W.D.; Kaczorowska, J.; Hoste, A.C.R.; Bakker, M.; Klein, M.; Loens, K.; Jebbink, M.F.; Matser, A.; Kinsella, C.M.; Rueda, P.; et al. Seasonal coronavirus protective immunity is short-lasting. Nat. Med. 2020, 26, 1691–1693. [Google Scholar] [CrossRef]
  54. Lustig, Y.; Gonen, T.; Meltzer, L.; Gilboa, M.; Indenbaum, V.; Cohen, C.; Amit, S.; Jaber, H.; Doolman, R.; Asraf, K.; et al. Superior immunogenicity and effectiveness of the third compared to the second BNT162b2 vaccine dose. Nat. Immunol. 2022, 23, 940–946. [Google Scholar] [CrossRef]
  55. Accorsi, E.K.; Britton, A.; Fleming-Dutra, K.E.; Smith, Z.R.; Shang, N.; Derado, G.; Miller, J.; Schrag, S.J.; Verani, J.R. Association Between 3 Doses of mRNA COVID-19 Vaccine and Symptomatic Infection Caused by the SARS-CoV-2 Omicron and Delta Variants. JAMA 2022, 327, 639–651. [Google Scholar] [CrossRef]
  56. Costa Clemens, S.A.; Weckx, L.; Clemens, R.; Almeida Mendes, A.V.; Ramos Souza, A.; Silveira, M.B.V.; da Guarda, S.N.F.; de Nobrega, M.M.; de Moraes Pinto, M.I.; Gonzalez, I.G.S.; et al. Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): A phase 4, non-inferiority, single blind, randomised study. Lancet 2022, 399, 521–529. [Google Scholar] [CrossRef]
  57. Regev-Yochay, G.; Gonen, T.; Gilboa, M.; Mandelboim, M.; Indenbaum, V.; Amit, S.; Meltzer, L.; Asraf, K.; Cohen, C.; Fluss, R.; et al. Efficacy of a Fourth Dose of COVID-19 mRNA Vaccine against Omicron. N. Engl. J. Med. 2022, 386, 1377–1380. [Google Scholar] [CrossRef] [PubMed]
  58. Chalkias, S.; Harper, C.; Vrbicky, K.; Walsh, S.R.; Essink, B.; Brosz, A.; McGhee, N.; Tomassini, J.E.; Chen, X.; Chang, Y.; et al. A Bivalent Omicron-Containing Booster Vaccine against COVID-19. N. Engl. J. Med. 2022, 387, 1279–1291. [Google Scholar] [CrossRef] [PubMed]
  59. Most Vulnerable Could Be Offered Booster COVID-19 Vaccines from September. Available online: https://www.gov.uk/government/news/most-vulnerable-could-be-offered-booster-covid-19-vaccines-from-september (accessed on 30 October 2022).
  60. Walls, A.C.; Park, Y.J.; Tortorici, M.A.; Wall, A.; McGuire, A.T.; Veesler, D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. Cell 2020, 181, 281–292.e6. [Google Scholar] [CrossRef] [PubMed]
  61. Lan, J.; Ge, J.; Yu, J.; Shan, S.; Zhou, H.; Fan, S.; Zhang, Q.; Shi, X.; Wang, Q.; Zhang, L.; et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature 2020, 581, 215–220. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  62. Shang, J.; Ye, G.; Shi, K.; Wan, Y.; Luo, C.; Aihara, H.; Geng, Q.; Auerbach, A.; Li, F. Structural basis of receptor recognition by SARS-CoV-2. Nature 2020, 581, 221–224. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  63. Wang, Q.; Zhang, Y.; Wu, L.; Niu, S.; Song, C.; Zhang, Z.; Lu, G.; Qiao, C.; Hu, Y.; Yuen, K.Y.; et al. Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2. Cell 2020, 181, 894–904.e9. [Google Scholar] [CrossRef] [PubMed]
  64. Yan, R.; Zhang, Y.; Li, Y.; Xia, L.; Guo, Y.; Zhou, Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 2020, 367, 1444–1448. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  65. Li, F.; Li, W.; Farzan, M.; Harrison, S.C. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science 2005, 309, 1864–1868. [Google Scholar] [CrossRef]
  66. Jackson, C.B.; Farzan, M.; Chen, B.; Choe, H. Mechanisms of SARS-CoV-2 entry into cells. Nat. Rev. Mol. Cell Biol. 2022, 23, 3–20. [Google Scholar] [CrossRef] [PubMed]
  67. V’Kovski, P.; Kratzel, A.; Steiner, S.; Stalder, H.; Thiel, V. Coronavirus biology and replication: Implications for SARS-CoV-2. Nat. Rev. Microbiol. 2021, 19, 155–170. [Google Scholar] [CrossRef]
  68. Barnes, C.O.; Jette, C.A.; Abernathy, M.E.; Dam, K.A.; Esswein, S.R.; Gristick, H.B.; Malyutin, A.G.; Sharaf, N.G.; Huey-Tubman, K.E.; Lee, Y.E.; et al. SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Nature 2020, 588, 682–687. [Google Scholar] [CrossRef] [PubMed]
  69. McLean, G.; Kamil, J.; Lee, B.; Moore, P.; Schulz, T.F.; Muik, A.; Sahin, U.; Türeci, Ö.; Pather, S. The Impact of Evolving SARS-CoV-2 Mutations and Variants on COVID-19 Vaccines. mBio 2022, 13, e0297921. [Google Scholar] [CrossRef] [PubMed]
  70. El-Shabasy, R.M.; Nayel, M.A.; Taher, M.M.; Abdelmonem, R.; Shoueir, K.R.; Kenawy, E.R. Three waves changes, new variant strains, and vaccination effect against COVID-19 pandemic. Int. J. Biol. Macromol. 2022, 204, 161–168. [Google Scholar] [CrossRef] [PubMed]
  71. Piccoli, L.; Park, Y.J.; Tortorici, M.A.; Czudnochowski, N.; Walls, A.C.; Beltramello, M.; Silacci-Fregni, C.; Pinto, D.; Rosen, L.E.; Bowen, J.E.; et al. Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology. Cell 2020, 183, 1024–1042.e21. [Google Scholar] [CrossRef] [PubMed]
  72. Yu, J.; Tostanoski, L.H.; Peter, L.; Mercado, N.B.; McMahan, K.; Mahrokhian, S.H.; Nkolola, J.P.; Liu, J.; Li, Z.; Chandrashekar, A.; et al. DNA vaccine protection against SARS-CoV-2 in rhesus macaques. Science 2020, 369, 806–811. [Google Scholar] [CrossRef] [PubMed]
  73. Corbett, K.S.; Flynn, B.; Foulds, K.E.; Francica, J.R.; Boyoglu-Barnum, S.; Werner, A.P.; Flach, B.; O’Connell, S.; Bock, K.W.; Minai, M.; et al. Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates. N. Engl. J. Med. 2020, 383, 1544–1555. [Google Scholar] [CrossRef]
  74. Mercado, N.B.; Zahn, R.; Wegmann, F.; Loos, C.; Chandrashekar, A.; Yu, J.; Liu, J.; Peter, L.; McMahan, K.; Tostanoski, L.H.; et al. Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature 2020, 586, 583–588. [Google Scholar] [CrossRef] [PubMed]
  75. Jackson, L.A.; Anderson, E.J.; Rouphael, N.G.; Roberts, P.C.; Makhene, M.; Coler, R.N.; McCullough, M.P.; Chappell, J.D.; Denison, M.R.; Stevens, L.J.; et al. An mRNA Vaccine against SARS-CoV-2—Preliminary Report. N. Engl. J. Med. 2020, 383, 1920–1931. [Google Scholar] [CrossRef]
  76. Walsh, E.E.; Frenck, R.W., Jr.; Falsey, A.R.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Neuzil, K.; Mulligan, M.J.; Bailey, R.; et al. Safety and Immunogenicity of Two RNA-Based COVID-19 Vaccine Candidates. N. Engl. J. Med. 2020, 383, 2439–2450. [Google Scholar] [CrossRef] [PubMed]
  77. Kanekiyo, M.; Joyce, M.G.; Gillespie, R.A.; Gallagher, J.R.; Andrews, S.F.; Yassine, H.M.; Wheatley, A.K.; Fisher, B.E.; Ambrozak, D.R.; Creanga, A.; et al. Mosaic nanoparticle display of diverse influenza virus hemagglutinins elicits broad B cell responses. Nat. Immunol. 2019, 20, 362–372. [Google Scholar] [CrossRef] [PubMed]
  78. Darricarrère, N.; Qiu, Y.; Kanekiyo, M.; Creanga, A.; Gillespie, R.A.; Moin, S.M.; Saleh, J.; Sancho, J.; Chou, T.H.; Zhou, Y.; et al. Broad neutralization of H1 and H3 viruses by adjuvanted influenza HA stem vaccines in nonhuman primates. Sci. Transl. Med. 2021, 13, eabe5449. [Google Scholar] [CrossRef]
  79. Pati, R.; Shevtsov, M.; Sonawane, A. Nanoparticle Vaccines Against Infectious Diseases. Front. Immunol. 2018, 9, 2224. [Google Scholar] [CrossRef] [Green Version]
  80. Yamashita, I.; Iwahori, K.; Kumagai, S. Ferritin in the field of nanodevices. Biochim. Biophys. Acta 2010, 1800, 846–857. [Google Scholar] [CrossRef] [PubMed]
  81. Worwood, M. Ferritin. Blood Rev. 1990, 4, 259–269. [Google Scholar] [CrossRef] [PubMed]
  82. Chakraborti, S.; Chakrabarti, P. Self-Assembly of Ferritin: Structure, Biological Function and Potential Applications in Nanotechnology. Adv. Exp. Med. Biol. 2019, 1174, 313–329. [Google Scholar] [PubMed]
  83. Lua, L.H.; Connors, N.K.; Sainsbury, F.; Chuan, Y.P.; Wibowo, N.; Middelberg, A.P. Bioengineering virus-like particles as vaccines. Biotechnol. Bioeng. 2014, 111, 425–440. [Google Scholar] [CrossRef] [PubMed]
  84. Joyce, M.G.; Chen, W.H.; Sankhala, R.S.; Hajduczki, A.; Thomas, P.V.; Choe, M.; Martinez, E.J.; Chang, W.C.; Peterson, C.E.; Morrison, E.B.; et al. SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity. Cell Rep. 2021, 37, 110143. [Google Scholar] [CrossRef] [PubMed]
  85. Wuertz, K.M.; Barkei, E.K.; Chen, W.H.; Martinez, E.J.; Lakhal-Naouar, I.; Jagodzinski, L.L.; Paquin-Proulx, D.; Gromowski, G.D.; Swafford, I.; Ganesh, A.; et al. A SARS-CoV-2 spike ferritin nanoparticle vaccine protects hamsters against Alpha and Beta virus variant challenge. NPJ Vaccines 2021, 6, 129. [Google Scholar] [CrossRef] [PubMed]
  86. Joyce, M.G.; King, H.A.D.; Elakhal-Naouar, I.; Ahmed, A.; Peachman, K.K.; Macedo Cincotta, C.; Subra, C.; Chen, R.E.; Thomas, P.V.; Chen, W.H.; et al. A SARS-CoV-2 ferritin nanoparticle vaccine elicits protective immune responses in nonhuman primates. Sci. Transl. Med. 2022, 14, eabi5735. [Google Scholar] [CrossRef] [PubMed]
  87. Bruun, T.U.J.; Andersson, A.C.; Draper, S.J.; Howarth, M. Engineering a Rugged Nanoscaffold to Enhance Plug-and-Display Vaccination. ACS Nano 2018, 12, 8855–8866. [Google Scholar] [CrossRef]
  88. Cohen, A.A.; Gnanapragasam, P.N.P.; Lee, Y.E.; Hoffman, P.R.; Ou, S.; Kakutani, L.M.; Keeffe, J.R.; Wu, H.J.; Howarth, M.; West, A.P.; et al. Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice. Science 2021, 371, 735–741. [Google Scholar] [CrossRef] [PubMed]
  89. Cohen, A.A.; van Doremalen, N.; Greaney, A.J.; Andersen, H.; Sharma, A.; Starr, T.N.; Keeffe, J.R.; Fan, C.; Schulz, J.E.; Gnanapragasam, P.N.P.; et al. Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models. Science 2022, 377, eabq0839. [Google Scholar] [CrossRef] [PubMed]
  90. COVID-19 Bivalent Vaccine Boosters. Available online: https://wwwfdagov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-bivalent-vaccine-boosters (accessed on 31 October 2022).
  91. Martinez, D.R.; Schäfer, A.; Leist, S.R.; De la Cruz, G.; West, A.; Atochina-Vasserman, E.N.; Lindesmith, L.C.; Pardi, N.; Parks, R.; Barr, M.; et al. Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice. Science 2021, 373, 991–998. [Google Scholar] [CrossRef] [PubMed]
  92. Krugman, S.; Katz, S.L. Attenuated smallpox vaccine. N. Engl. J. Med. 1970, 282, 344. [Google Scholar] [PubMed]
  93. Yokote, H.; Shinmura, Y.; Kanehara, T.; Maruno, S.; Kuranaga, M.; Matsui, H.; Hashizume, S. Safety of attenuated smallpox vaccine LC16m8 in immunodeficient mice. Clin. Vaccine Immunol. 2014, 21, 1261–1266. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  94. Gershon, A.A. Live-attenuated varicella vaccine. Infect. Dis. Clin. N. Am. 2001, 15, 65–81. [Google Scholar] [CrossRef] [PubMed]
  95. Gershon, A.A.; Gershon, M.D.; Shapiro, E.D. Live Attenuated Varicella Vaccine: Prevention of Varicella and of Zoster. J. Infect. Dis. 2021, 224 (Suppl. 2), S387–S397. [Google Scholar] [CrossRef]
  96. Davis, E.H.; Beck, A.S.; Li, L.; White, M.M.; Greenberg, M.B.; Thompson, J.K.; Widen, S.G.; Barrett, A.D.T.; Bourne, N. Japanese encephalitis virus live attenuated vaccine strains display altered immunogenicity, virulence and genetic diversity. NPJ Vaccines 2021, 6, 112. [Google Scholar] [CrossRef]
  97. Ngwe Tun, M.M.; Kyaw, A.K.; Nwe, K.M.; Inoue, S.; Thant, K.Z.; Morita, K. Effectiveness of the SA 14-14-2 Live-Attenuated Japanese Encephalitis Vaccine in Myanmar. Vaccines 2021, 9, 568. [Google Scholar] [CrossRef]
  98. Barrett, A.D.T. Yellow fever live attenuated vaccine: A very successful live attenuated vaccine but still we have problems controlling the disease. Vaccine 2017, 35, 5951–5955. [Google Scholar] [CrossRef] [PubMed]
  99. Collins, N.D.; Barrett, A.D. Live Attenuated Yellow Fever 17D Vaccine: A Legacy Vaccine Still Controlling Outbreaks in Modern Day. Curr. Infect. Dis. Rep. 2017, 19, 14. [Google Scholar] [CrossRef] [PubMed]
  100. Jones, T. IMVAMUNE, an attenuated modified vaccinia Ankara virus vaccine for smallpox infection. Curr. Opin. Mol. Ther. 2008, 10, 407–417. [Google Scholar] [PubMed]
  101. Sricharoenchai, S.; Lapphra, K.; Chuenkitmongkol, S.; Phongsamart, W.; Bouckenooghe, A.; Wittawatmongkol, O.; Rungmaitree, S.; Chokephaibulkit, K. Immunogenicity of a Live Attenuated Chimeric Japanese Encephalitis Vaccine as a Booster Dose After Primary Vaccination with Live Attenuated SA14-14-2 Vaccine: A Phase IV Study in Thai Children. Pediatr. Infect. Dis. J. 2017, 36, e45–e47. [Google Scholar] [CrossRef] [PubMed]
  102. Jiang, F.; Zhang, R.; Guan, Q.; Mu, Q.; He, P.; Ye, X.; Wang, W.; Quan, J.; Li, J.; Liang, L.; et al. Immunogenicity and safety of a live attenuated varicella vaccine in children 1–12 years of age: A randomized, blinded, controlled, non-inferiority phase 3 clinical trial. Contemp. Clin. Trials 2021, 107, 106489. [Google Scholar] [CrossRef]
  103. Verheust, C.; Goossens, M.; Pauwels, K.; Breyer, D. Biosafety aspects of modified vaccinia virus Ankara (MVA)-based vectors used for gene therapy or vaccination. Vaccine 2012, 30, 2623–2632. [Google Scholar] [CrossRef] [Green Version]
  104. Lin, I.Y.; Van, T.T.; Smooker, P.M. Live-Attenuated Bacterial Vectors: Tools for Vaccine and Therapeutic Agent Delivery. Vaccines 2015, 3, 940–972. [Google Scholar] [CrossRef] [Green Version]
  105. Toussaint, B.; Chauchet, X.; Wang, Y.; Polack, B.; Le Gouëllec, A. Live-attenuated bacteria as a cancer vaccine vector. Expert Rev. Vaccines 2013, 12, 1139–1154. [Google Scholar] [CrossRef]
  106. Remy-Ziller, C.; Thioudellet, C.; Hortelano, J.; Gantzer, M.; Nourtier, V.; Claudepierre, M.C.; Sansas, B.; Préville, X.; Bendjama, K.; Quemeneur, E.; et al. Sequential administration of MVA-based vaccines and PD-1/PD-L1-blocking antibodies confers measurable benefits on tumor growth and survival: Preclinical studies with MVA-βGal and MVA-MUC1 (TG4010) in a murine tumor model. Hum. Vaccines Immunother. 2018, 14, 140–145. [Google Scholar] [CrossRef] [Green Version]
  107. Li, L.L.; Wang, H.R.; Zhou, Z.Y.; Luo, J.; Xiao, X.Q.; Wang, X.L.; Li, J.T.; Zhou, Y.B.; Zeng, Y. One-prime multi-boost strategy immunization with recombinant DNA, adenovirus, and MVA vector vaccines expressing HPV16 L1 induces potent, sustained, and specific immune response in mice. Antivir. Res. 2016, 128, 20–27. [Google Scholar] [CrossRef]
  108. Brett, D.L.C.L.M.; Heinz-Jürgen, T.; Rice, C.M. Flaviviridae. In Fields Virology, 6th ed.; Knipe, D.M., Ed.; Lippincott Willims & Wilkins: Philadelphia, PA, USA, 2013; p. 712. [Google Scholar]
  109. Wieten, R.W.; Jonker, E.F.; van Leeuwen, E.M.; Remmerswaal, E.B.; Ten Berge, I.J.; de Visser, A.W.; van Genderen, P.J.; Goorhuis, A.; Visser, L.G.; Grobusch, M.P.; et al. A Single 17D Yellow Fever Vaccination Provides Lifelong Immunity; Characterization of Yellow-Fever-Specific Neutralizing Antibody and T-Cell Responses after Vaccination. PLoS ONE 2016, 11, e0149871. [Google Scholar] [CrossRef]
  110. Grobusch, M.P.; van Aalst, M.; Goorhuis, A. Yellow fever vaccination—Once in a lifetime? Travel Med. Infect. Dis. 2017, 15, 1–2. [Google Scholar] [CrossRef] [PubMed]
  111. Franco, D.; Li, W.; Qing, F.; Stoyanov, C.T.; Moran, T.; Rice, C.M.; Ho, D.D. Evaluation of yellow fever virus 17D strain as a new vector for HIV-1 vaccine development. Vaccine 2010, 28, 5676–5685. [Google Scholar] [CrossRef] [PubMed]
  112. Blyth, D.M.; Liang, Z.; Williams, M.; Murray, C.K. Immune interference revisited: Impact of live-attenuated influenza vaccine prior to yellow fever vaccination. Vaccine 2022, 40, 961–966. [Google Scholar] [CrossRef] [PubMed]
  113. Boudewijns, R.; Ma, J.; Neyts, J.; Dallmeier, K. A novel therapeutic HBV vaccine candidate induces strong polyfunctional cytotoxic T cell responses in mice. JHEP Rep. 2021, 3, 100295. [Google Scholar] [CrossRef] [PubMed]
  114. Kwek, S.S.; Watanabe, S.; Chan, K.R.; Ong, E.Z.; Tan, H.C.; Ng, W.C.; Nguyen, M.T.X.; Gan, E.S.; Zhang, S.L.; Chan, K.W.K.; et al. A systematic approach to the development of a safe live attenuated Zika vaccine. Nat. Commun. 2018, 9, 1031. [Google Scholar] [CrossRef] [Green Version]
  115. Oreshkova, N.; Myeni, S.K.; Mishra, N.; Albulescu, I.C.; Dalebout, T.J.; Snijder, E.J.; Bredenbeek, P.J.; Dallmeier, K.; Kikkert, M. A Yellow Fever 17D Virus Replicon-Based Vaccine Platform for Emerging Coronaviruses. Vaccines 2021, 9, 1492. [Google Scholar] [CrossRef]
  116. Sanchez-Felipe, L.; Vercruysse, T.; Sharma, S.; Ma, J.; Lemmens, V.; Van Looveren, D.; Arkalagud Javarappa, M.P.; Boudewijns, R.; Malengier-Devlies, B.; Liesenborghs, L.; et al. A single-dose live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate. Nature 2021, 590, 320–325. [Google Scholar] [CrossRef]
  117. Chiuppesi, F.; Salazar, M.D.; Contreras, H.; Nguyen, V.H.; Martinez, J.; Park, Y.; Nguyen, J.; Kha, M.; Iniguez, A.; Zhou, Q.; et al. Development of a multi-antigenic SARS-CoV-2 vaccine candidate using a synthetic poxvirus platform. Nat. Commun. 2020, 11, 6121. [Google Scholar] [CrossRef]
  118. García-Arriaza, J.; Garaigorta, U.; Pérez, P.; Lázaro-Frías, A.; Zamora, C.; Gastaminza, P.; Del Fresno, C.; Casasnovas, J.M.; Sorzano CÓ, S.; Sancho, D.; et al. COVID-19 vaccine candidates based on modified vaccinia virus Ankara expressing the SARS-CoV-2 spike induce robust T- and B-cell immune responses and full efficacy in mice. J. Virol. 2021, 95, e02260-20. [Google Scholar] [CrossRef]
  119. Routhu, N.K.; Cheedarla, N.; Gangadhara, S.; Bollimpelli, V.S.; Boddapati, A.K.; Shiferaw, A.; Rahman, S.A.; Sahoo, A.; Edara, V.V.; Lai, L.; et al. A modified vaccinia Ankara vector-based vaccine protects macaques from SARS-CoV-2 infection, immune pathology, and dysfunction in the lungs. Immunity 2021, 54, 542–556.e9. [Google Scholar] [CrossRef]
  120. Liu, R.; Americo, J.L.; Cotter, C.A.; Earl, P.L.; Erez, N.; Peng, C.; Moss, B. MVA Vector Vaccines Inhibit SARS CoV-2 Replication in Upper and Lower Respiratory Tracts of Transgenic Mice and Prevent Lethal Disease. bioRxiv 2021. [Google Scholar] [CrossRef]
  121. Tscherne, A.; Schwarz, J.H.; Rohde, C.; Kupke, A.; Kalodimou, G.; Limpinsel, L.; Okba, N.M.A.; Bošnjak, B.; Sandrock, I.; Odak, I.; et al. Immunogenicity and efficacy of the COVID-19 candidate vector vaccine MVA-SARS-2-S in preclinical vaccination. Proc. Natl. Acad. Sci. USA 2021, 118, e2026207118. [Google Scholar] [CrossRef] [PubMed]
  122. Lin, W.W.; Moran, E.; Adams, R.J.; Sievers, R.E.; Hauer, D.; Godin, S.; Griffin, D.E. A durable protective immune response to wild-type measles virus infection of macaques is due to viral replication and spread in lymphoid tissues. Sci. Transl. Med. 2020, 12, eaax7799. [Google Scholar] [CrossRef] [PubMed]
  123. Griffin, D.E. Measles Vaccine. Viral Immunol. 2018, 31, 86–95. [Google Scholar] [CrossRef] [PubMed]
  124. Lu, M.; Dravid, P.; Zhang, Y.; Trivedi, S.; Li, A.; Harder, O.; Kc, M.; Chaiwatpongsakorn, S.; Zani, A.; Kenney, A.; et al. A safe and highly efficacious measles virus-based vaccine expressing SARS-CoV-2 stabilized prefusion spike. Proc. Natl. Acad. Sci. USA 2021, 118, e2026153118. [Google Scholar] [CrossRef]
  125. Wang, D.; Tai, P.W.L.; Gao, G. Adeno-associated virus vector as a platform for gene therapy delivery. Nat. Rev. Drug Discov. 2019, 18, 358–378. [Google Scholar] [CrossRef]
  126. Li, C.; Samulski, R.J. Engineering adeno-associated virus vectors for gene therapy. Nat. Rev. Genet. 2020, 21, 255–272. [Google Scholar] [CrossRef]
  127. Li, X.; Cao, H.; Wang, Q.; Di, B.; Wang, M.; Lu, J.; Pan, L.; Yang, L.; Mei, M.; Pan, X.; et al. Novel AAV-based genetic vaccines encoding truncated dengue virus envelope proteins elicit humoral immune responses in mice. Microbes Infect. 2012, 14, 1000–1007. [Google Scholar] [CrossRef]
  128. Zhu, F.; Wang, Y.; Xu, Z.; Qu, H.; Zhang, H.; Niu, L.; Xue, H.; Jing, D.; He, H. Novel adeno-associated virus-based genetic vaccines encoding hepatitis C virus E2 glycoprotein elicit humoral immune responses in mice. Mol. Med. Rep. 2019, 19, 1016–1023. [Google Scholar] [CrossRef]
  129. Lin, J.; Calcedo, R.; Vandenberghe, L.H.; Bell, P.; Somanathan, S.; Wilson, J.M. A new genetic vaccine platform based on an adeno-associated virus isolated from a rhesus macaque. J. Virol. 2009, 83, 12738–12750. [Google Scholar] [CrossRef]
  130. Zabaleta, N.; Dai, W.; Bhatt, U.; Hérate, C.; Maisonnasse, P.; Chichester, J.A.; Sanmiguel, J.; Estelien, R.; Michalson, K.T.; Diop, C.; et al. An AAV-based, room-temperature-stable, single-dose COVID-19 vaccine provides durable immunogenicity and protection in non-human primates. Cell Host Microbe 2021, 29, 1437–1453.e8. [Google Scholar] [CrossRef] [PubMed]
  131. Wu, F.; Luo, S.; Zhang, Y.; Ou, Y.; Wang, H.; Guo, Z.; He, C.; Bai, S.; He, P.; Jiang, M.; et al. Single-shot AAV-vectored vaccine against SARS-CoV-2 with fast and long-lasting immunity. Acta Pharm. Sin. B, 2022; in press. [Google Scholar]
  132. Ahmed, R.; Gray, D. Immunological memory and protective immunity: Understanding their relation. Science 1996, 272, 54–60. [Google Scholar] [CrossRef] [PubMed]
  133. Zhao, J.; Zhao, J.; Perlman, S. T cell responses are required for protection from clinical disease and for virus clearance in severe acute respiratory syndrome coronavirus-infected mice. J. Virol. 2010, 84, 9318–9325. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  134. Kaneko, N.; Kuo, H.H.; Boucau, J.; Farmer, J.R.; Allard-Chamard, H.; Mahajan, V.S.; Piechocka-Trocha, A.; Lefteri, K.; Osborn, M.; Bals, J.; et al. Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19. Cell 2020, 183, 143–157.e13. [Google Scholar] [CrossRef]
  135. Seder, R.A.; Darrah, P.A.; Roederer, M. T-cell quality in memory and protection: Implications for vaccine design. Nat. Rev. Immunol. 2008, 8, 247–258. [Google Scholar] [CrossRef]
  136. Swain, S.L.; McKinstry, K.K.; Strutt, T.M. Expanding roles for CD4⁺ T cells in immunity to viruses. Nat. Rev. Immunol. 2012, 12, 136–148. [Google Scholar] [CrossRef]
  137. Wang, C.Y.; Lin, F.; Ding, S.; Peng, W.-J. Designer Peptides and Proteins for the Detection, Prevention and Treatment of Coronavirus Disease, 2019 (COVID 19). WO2021/168305A1.2020. WIPO. 2021. Available online: https://patentscope2.wipo.int/search/ja/detail.jsf?docId=WO2021168305 (accessed on 2 November 2022).
  138. Wang, C.Y.; Hwang, K.P.; Kuo, H.K.; Peng, W.J.; Shen, Y.H.; Kuo, B.S.; Huang, J.H.; Liu, H.; Ho, Y.H.; Lin, F.; et al. A multitope SARS-CoV-2 vaccine provides long-lasting B cell and T cell immunity against Delta and Omicron variants. J. Clin. Investig. 2022, 132, e157707. [Google Scholar] [CrossRef] [PubMed]
  139. Li, M.; Zeng, J.; Li, R.; Wen, Z.; Cai, Y.; Wallin, J.; Shu, Y.; Du, X.; Sun, C. Rational Design of a Pan-Coronavirus Vaccine Based on Conserved CTL Epitopes. Viruses 2021, 13, 333. [Google Scholar] [CrossRef]
  140. Prakash, S.; Srivastava, R.; Coulon, P.G.; Dhanushkodi, N.R.; Chentoufi, A.A.; Tifrea, D.F.; Edwards, R.A.; Figueroa, C.J.; Schubl, S.D.; Hsieh, L.; et al. Genome-Wide B Cell, CD4(+), and CD8(+) T Cell Epitopes That Are Highly Conserved between Human and Animal Coronaviruses, Identified from SARS-CoV-2 as Targets for Preemptive Pan-Coronavirus Vaccines. J. Immunol. 2021, 206, 2566–2582. [Google Scholar] [CrossRef]
  141. Atmar, R.L.; Lyke, K.E.; Deming, M.E.; Jackson, L.A.; Branche, A.R.; El Sahly, H.M.; Rostad, C.A.; Martin, J.M.; Johnston, C.; Rupp, R.E.; et al. Homologous and Heterologous COVID-19 Booster Vaccinations. N. Engl. J. Med. 2022, 386, 1046–1057. [Google Scholar] [CrossRef]
Vaccines 10 02035 g001 550
Figure 1. Phylogenetic tree using neighbor-joining method and schematic diagram of mutation sites. Phylogenetic tree was generated by MEGAsoftware (version 11.0.13). The genomes of CoV variants were retrieved from GISAID (https://www.gisaid.org/, accessed on 2 November 2022). WIV04: EPI_ISL_402124; Alpha: EPI_ISL_674612; Beta: EPI_ISL_940877; Gamma: EPI_ISL_2777382; Delta: EPI_ISL_1758376; Omicron BA.1: EPI_ISL_6795848; Omicron BA.1.1: EPI_ISL_8724963; Omicron BA.2: EPI_ISL_8135710; Omicron BA.4: EPI_ISL_11542550; Omicron BA.5: EPI_ISL_11542604; Omicron BA.2.12.1: EPI_ISL_11368598; Omicron BA.2.11: EPI_ISL_9862290; Omicron BA.2.13: EPI_ISL_9512109.
Figure 1. Phylogenetic tree using neighbor-joining method and schematic diagram of mutation sites. Phylogenetic tree was generated by MEGAsoftware (version 11.0.13). The genomes of CoV variants were retrieved from GISAID (https://www.gisaid.org/, accessed on 2 November 2022). WIV04: EPI_ISL_402124; Alpha: EPI_ISL_674612; Beta: EPI_ISL_940877; Gamma: EPI_ISL_2777382; Delta: EPI_ISL_1758376; Omicron BA.1: EPI_ISL_6795848; Omicron BA.1.1: EPI_ISL_8724963; Omicron BA.2: EPI_ISL_8135710; Omicron BA.4: EPI_ISL_11542550; Omicron BA.5: EPI_ISL_11542604; Omicron BA.2.12.1: EPI_ISL_11368598; Omicron BA.2.11: EPI_ISL_9862290; Omicron BA.2.13: EPI_ISL_9512109.
Vaccines 10 02035 g001
Vaccines 10 02035 g002 550
Figure 2. Infections and deaths since June 2021 to October 2022. Infections of SARS-CoV-2 sharply increased and deaths rate has been gradually declining in the early 2022 since Omicron variant became the predominant epidemic variant. (A), The weekly number of new cases and new deaths worldwide (from June 2021 to October 2022) released by the WHO. (B) Global death rates due to COVID-19 infection (ratio of deaths to infections) from June 2021 to October 2022.
Figure 2. Infections and deaths since June 2021 to October 2022. Infections of SARS-CoV-2 sharply increased and deaths rate has been gradually declining in the early 2022 since Omicron variant became the predominant epidemic variant. (A), The weekly number of new cases and new deaths worldwide (from June 2021 to October 2022) released by the WHO. (B) Global death rates due to COVID-19 infection (ratio of deaths to infections) from June 2021 to October 2022.
Vaccines 10 02035 g002
Vaccines 10 02035 g003 550
Figure 3. Applied platform for next-generation anti-coronavirus R&D. Booster immunization with approved vaccines (A), Vaccines with more complex sources of spike protein RBD (B), Live attenuated viral vaccine delivered SARS-CoV-2 antigen (C), Subunit vaccines with T-cell epitopes (D). More cutting-edge vaccine design using AI technology (E) can be used for the prevention of infectious diseases.
Figure 3. Applied platform for next-generation anti-coronavirus R&D. Booster immunization with approved vaccines (A), Vaccines with more complex sources of spike protein RBD (B), Live attenuated viral vaccine delivered SARS-CoV-2 antigen (C), Subunit vaccines with T-cell epitopes (D). More cutting-edge vaccine design using AI technology (E) can be used for the prevention of infectious diseases.
Vaccines 10 02035 g003
Table
Table 1. Review of next-generation coronavirus vaccines in development.
Table 1. Review of next-generation coronavirus vaccines in development.
Type of VaccineVaccineSponsorPropertiesStatus
Booster immunization with approved vaccinesComirnatyPfizer-BioNTechrBoost used a bivalent vaccine using the same technology of approved vaccineapproved by FDA
SpikevaxModernaapproved by FDA
Vaccines with more complex sources of spike protein RBDSpFNU.S. Army Medical Research and Development Command Ferritin nanoparticle with prefusion- stabilized spike antigens from the Wuhan strain of SARS- CoV-2Phase 1
Mosaic-4a/4b/8California Institute of TechnologyFerritin nanoparticle with prefusion- spike antigens from different CoronavirusPreclinical
Chimera 1 /4University of North Carolina at Chapel HillChimeric spike mRNA vaccines with epitops come from differet Coronavirus Preclinical
Live attenuated viral vaccine delivered SARS-CoV-2 antigenYF-S0KU Leuven Department of Microbiology, Belgium.live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express a noncleavable prefusion form of the SARS-CoV-2 spike antigen.Preclinical
MVA-SARS-2-SUniversitätsklinikum Hamburg-Eppendorfrecombinant MVA expressing full-length SARS-CoV-2 spike (S) protein Phase 1
rMeV-preS The Ohio State Universitymeasles virus (rMeV) vaccine strain as the backbone expressing SARS-CoV-2 spike (S) protein and its receptor binding domain (RBD) Preclinical
Subunit vaccines with T-cell epitopesUB-612United Biomedical Inc., Asiarecombinant subunit vaccine expressing the spike 1 (S1)-RBD fused with a single-chain Fc protein (S1-RBD-sFc), 5 Th cell, and CTL epitope peptides from the nucleocapsid (N), membrane (M), and S2 proteins of sarbecovirusesPhase 1
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Li, L.; Wei, Y.; Yang, H.; Yan, J.; Li, X.; Li, Z.; Zhao, Y.; Liang, H.; Wang, H. Advances in Next-Generation Coronavirus Vaccines in Response to Future Virus Evolution. Vaccines 2022, 10, 2035. https://doi.org/10.3390/vaccines10122035

AMA Style

Li L, Wei Y, Yang H, Yan J, Li X, Li Z, Zhao Y, Liang H, Wang H. Advances in Next-Generation Coronavirus Vaccines in Response to Future Virus Evolution. Vaccines. 2022; 10(12):2035. https://doi.org/10.3390/vaccines10122035

Chicago/Turabian Style

Li, Lili, Yangyang Wei, Han Yang, Junyu Yan, Xin Li, Ziqian Li, Yuxiu Zhao, Hongyang Liang, and Hui Wang. 2022. "Advances in Next-Generation Coronavirus Vaccines in Response to Future Virus Evolution" Vaccines 10, no. 12: 2035. https://doi.org/10.3390/vaccines10122035

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop