Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Antibodies antibodies	3.0	7.1	2012	22.8 Days	CHF 1800
COVID covid	-	-	2021	20.3 Days	CHF 1000
Pathogens pathogens	3.3	6.4	2012	15.3 Days	CHF 2200
Vaccines vaccines	5.2	8.9	2013	18.6 Days	CHF 2700
Viruses viruses	3.8	7.3	2009	17.1 Days	CHF 2600

9 pages, 282 KiB

Open AccessArticle

by Patrícia Coelho, Manuel Martins, Catarina Gavinhos, Joana Liberal, Ema Cabral, Inês Ribeiro and Francisco Rodrigues

COVID 2023, 3(11), 1698-1706; https://doi.org/10.3390/covid3110117 - 19 Nov 2023

Viewed by 1910

Abstract

Body mass index has been studied as one of the factors that negatively influences COVID-19. In this work, we intend to analyze this influence. A representative sample of the population of Beira Interior was used (around 2%), on which immunity research and a [...] Read more.

Body mass index has been studied as one of the factors that negatively influences COVID-19. In this work, we intend to analyze this influence. A representative sample of the population of Beira Interior was used (around 2%), on which immunity research and a socio-demographic survey were carried out. It was found that obesity influences the vaccination rate, and that all other variables analyzed were not influenced by body mass index. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

12 pages, 1186 KiB

Open AccessArticle

Hybrid Immunity Results in Enhanced and More Sustained Antibody Responses after the Second Sinovac-CoronaVac Dose in a Brazilian Cohort: DETECTCoV-19 Cohort

by Bárbara Batista Salgado, Aguyda Rayany Cavalcante Barbosa, Ana Ruth Arcanjo, Daniel Barros de Castro, Tatyana Costa Amorim Ramos, Felipe Naveca, Daniel M. Altmann, Rosemary J. Boyton, Jaila Dias Borges Lalwani and Pritesh Lalwani

Viruses 2023, 15(10), 1987; https://doi.org/10.3390/v15101987 - 23 Sep 2023

Cited by 1 | Viewed by 1830

Abstract

We measured anti-SARS-CoV-2 antibody responses before and after CoronaVac (inactivated) vaccination in a case–control study performed in CoronaVac-immunized individuals participating in a longitudinal prospective study of adults in Manaus (DETECTCoV-19). Antibody responses were measured by standard serological immunoassays. Peak anti-S-RBD and neutralizing RBD-ACE2 [...] Read more.

We measured anti-SARS-CoV-2 antibody responses before and after CoronaVac (inactivated) vaccination in a case–control study performed in CoronaVac-immunized individuals participating in a longitudinal prospective study of adults in Manaus (DETECTCoV-19). Antibody responses were measured by standard serological immunoassays. Peak anti-S-RBD and neutralizing RBD-ACE2 blocking antibody responses after two doses of CoronaVac vaccine were similar in vaccine breakthrough cases (n = 9) and matched controls (n = 45). Individuals with hybrid immunity resulting from prior SARS-CoV-2 infection followed by vaccination (n = 22) had elevated levels of anti-N, anti-S-RBD and RBD-ACE2 blocking antibodies after the second vaccine dose compared to infection-naïve individuals (n = 48). Post-vaccination SARS-CoV-2-specific antibody responses rapidly waned in infection-naïve individuals. Antibody responses wane after vaccination, making individuals susceptible to infection by SARS-CoV-2 variants. These findings support the need for booster doses after primary vaccination. Population antibody serosurveys provide critical information toward implementing optimal timing of booster doses. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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19 pages, 1855 KiB

Open AccessReview

A Comprehensive Analysis of Structural and Functional Changes Induced by SARS-CoV-2 Spike Protein Mutations

by Aganze Gloire-Aimé Mushebenge, Samuel Chima Ugbaja, Nonkululeko Avril Mbatha, Rene B. Khan and Hezekiel M. Kumalo

COVID 2023, 3(9), 1454-1472; https://doi.org/10.3390/covid3090100 - 16 Sep 2023

Cited by 5 | Viewed by 2892

Abstract

The emergence of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has sparked intense research on its spike protein, which is essential for viral entrance into host cells. Viral reproduction and transmission, host immune response regulation, receptor recognition and host cell entrance mechanisms, [...] Read more.

The emergence of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, has sparked intense research on its spike protein, which is essential for viral entrance into host cells. Viral reproduction and transmission, host immune response regulation, receptor recognition and host cell entrance mechanisms, as well as structural and functional effects have all been linked to mutations in the spike protein. Spike protein mutations can also result in immune evasion mechanisms that impair vaccine effectiveness and escape, and they are linked to illness severity and clinical consequences. Numerous studies have been conducted to determine the effects of these mutations on the spike protein structure and how it interacts with host factors. These results have important implications for the design and development of medicines and vaccines based on spike proteins as well as for the assessment of those products’ efficiency against newly discovered spike protein mutations. This paper gives a general overview of how spike protein mutations are categorized and named. It further looks at the links between spike protein mutations and clinical outcomes, illness severity, unanswered problems, and future research prospects. Additionally, explored are the effects of these mutations on vaccine effectiveness as well as the possible therapeutic targeting of spike protein mutations. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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10 pages, 1801 KiB

Open AccessArticle

In Vitro Antibody-Dependent Enhancement of SARS-CoV-2 Infection Could Be Abolished by Adding Human IgG

by Xun Wang, Minghui Li, Panpan Lu, Chen Li, Chaoyue Zhao, Xiaoyu Zhao, Rui Qiao, Yuchen Cui, Yanjia Chen, Jiayan Li, Guonan Cai and Pengfei Wang

Pathogens 2023, 12(9), 1108; https://doi.org/10.3390/pathogens12091108 - 30 Aug 2023

Cited by 3 | Viewed by 2187

Abstract

Evidence of antibody-dependent enhancement (ADE) of other viruses has raised concerns about the safety of SARS-CoV-2 vaccines and antibody therapeutics. In vitro studies have shown ADE of SARS-CoV-2 infection. In this study, we also found that vaccination/convalescent sera and some approved monoclonal antibodies [...] Read more.

Evidence of antibody-dependent enhancement (ADE) of other viruses has raised concerns about the safety of SARS-CoV-2 vaccines and antibody therapeutics. In vitro studies have shown ADE of SARS-CoV-2 infection. In this study, we also found that vaccination/convalescent sera and some approved monoclonal antibodies can enhance SARS-CoV-2 infection of FcR-expressing B cells in vitro. However, the enhancement of SARS-CoV-2 infection can be prevented by blocking Fc–FcR interaction through the addition of human serum/IgG or the introduction of mutations in the Fc portion of the antibody. It should be noted that ADE activity observed on FcR-expressing cells in vitro may not necessarily reflect the situation in vivo; therefore, animal and clinical data should be included for ADE evaluation. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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14 pages, 7245 KiB

Open AccessArticle

Clinical Utility of SARS-CoV-2 Antibody Titer Multiplied by Binding Avidity of Receptor-Binding Domain (RBD) in Monitoring Protective Immunity and Clinical Severity

by Etsuhisa Takahashi, Takako Sawabuchi, Tetsuya Homma, Yosuke Fukuda, Hironori Sagara, Takeshi Kinjo, Kaori Fujita, Shigeru Suga, Takashi Kimoto, Satoko Sakai, Keiko Kameda and Hiroshi Kido

Viruses 2023, 15(8), 1662; https://doi.org/10.3390/v15081662 - 30 Jul 2023

Cited by 3 | Viewed by 2044

Abstract

Conventional serum antibody titer, which expresses antibody level, does not provide antigen binding avidity of the variable region of the antibody, which is essential for the defense response to infection. Here, we quantified anti-SARS-CoV-2 antibody binding avidity to the receptor-binding domain (RBD) by [...] Read more.

Conventional serum antibody titer, which expresses antibody level, does not provide antigen binding avidity of the variable region of the antibody, which is essential for the defense response to infection. Here, we quantified anti-SARS-CoV-2 antibody binding avidity to the receptor-binding domain (RBD) by competitive binding-inhibition activity (IC50) between SARS-CoV-2 S1 antigen immobilized on the DCP microarray and various RBD doses added to serum and expressed as 1/IC50 nM. The binding avidity analyzed under equilibrium conditions of antigen–antibody binding reaction is different from the avidity index measured with the chaotropic agent, such as urea, under nonequilibrium and short-time conditions. Quantitative determination of the infection-protection potential of antibodies was assessed by ABAT (antigen binding avidity antibody titer), which was calculated by the quantity (level) × quality (binding avidity) of antibodies. The binding avidity correlated strongly (r = 0.811) with cell-based virus-neutralizing activity. Maturation of the protective antibody induced by repeated vaccinations or SARS-CoV-2 infection was classified into three categories of ABAT, such as an initial, low, and high ABAT. Antibody maturity correlated with the clinical severity of COVID-19. Once a mature high binding avidity was achieved, it was maintained for at least 6–8 months regardless of the subsequent change in the antibody levels. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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11 pages, 453 KiB

Open AccessArticle

Prognostic Value of Creatinine Levels at Admission on Disease Progression and Mortality in Patients with COVID-19—An Observational Retrospective Study

by Antonio Russo, Mariantonietta Pisaturo, Caterina Monari, Federica Ciminelli, Paolo Maggi, Enrico Allegorico, Ivan Gentile, Vincenzo Sangiovanni, Vincenzo Esposito, Valeria Gentile, Giosuele Calabria, Raffaella Pisapia, Canio Carriero, Alfonso Masullo, Elio Manzillo, Grazia Russo, Roberto Parrella, Giuseppina Dell’Aquila, Michele Gambardella, Antonio Ponticiello, Lorenzo Onorato and Nicola Coppola Show full author list Hide full author list

Pathogens 2023, 12(8), 973; https://doi.org/10.3390/pathogens12080973 - 25 Jul 2023

Cited by 7 | Viewed by 2044

Abstract

Introduction: Acute kidney disease and chronic kidney disease are considered conditions that can increase the mortality and severity of COVID-19. However, few studies have investigated the impact of creatinine levels on COVID-19 progression in patients without a history of chronic kidney disease. The [...] Read more.

Introduction: Acute kidney disease and chronic kidney disease are considered conditions that can increase the mortality and severity of COVID-19. However, few studies have investigated the impact of creatinine levels on COVID-19 progression in patients without a history of chronic kidney disease. The aim of the study was to assess the impact of creatinine levels at hospital admission on COVID-19 progression and mortality. Methods: We performed a multicenter, observational, retrospective study involving seventeen COVID-19 Units in the Campania region in southern Italy. All adult (≥18 years) patients, hospitalized with a diagnosis of SARS-CoV-2 infection confirmed by a positive reverse transcriptase-polymerase chain reaction on a naso-oropharyngeal swab, from 28 February 2020 to 31 May 2021, were enrolled in the CoviCamp cohort. Results: Evaluating inclusion/exclusion criteria, 1357 patients were included. Considering in-hospital mortality and creatinine value at admission, the best cut-off point to discriminate a death during hospitalization was 1.115 mg/dL. The logistic regression demonstrated that factors independently associated with mortality were age (OR 1.082, CI: 1.054–1.110), Charlson Comorbidity Index (CCI) (OR 1.341, CI: 1.178–1.526), and an abnormal creatinine value at admission, defined as equal to or above 1.12 mg/dL (OR 2.233, CI: 1.373–3.634). Discussion: In conclusion, our study is in line with previous studies confirming that the creatinine serum level can predict mortality in COVID-19 patients and defining that the best cut-off of the creatinine serum level at admission to predict mortality was 1.12 mg/dL. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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17 pages, 3021 KiB

Open AccessArticle

Human Post-Translational SUMOylation Modification of SARS-CoV-2 Nucleocapsid Protein Enhances Its Interaction Affinity with Itself and Plays a Critical Role in Its Nuclear Translocation

by Vipul Madahar, Runrui Dang, Quanqing Zhang, Chuchu Liu, Victor G. J. Rodgers and Jiayu Liao

Viruses 2023, 15(7), 1600; https://doi.org/10.3390/v15071600 - 21 Jul 2023

Cited by 6 | Viewed by 6423

Abstract

Viruses, such as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infect hosts and take advantage of host cellular machinery for genome replication and new virion production. Identifying and elucidating host pathways for viral infection is critical for understanding the development of the viral [...] Read more.

Viruses, such as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infect hosts and take advantage of host cellular machinery for genome replication and new virion production. Identifying and elucidating host pathways for viral infection is critical for understanding the development of the viral life cycle and novel therapeutics. The SARS-CoV-2 N protein is critical for viral RNA (vRNA) genome packaging in new virion formation. Using our quantitative Förster energy transfer/Mass spectrometry (qFRET/MS) coupled method and immunofluorescence imaging, we identified three SUMOylation sites of the SARS-CoV-2 N protein. We found that (1) Small Ubiquitin-like modifier (SUMO) modification in Nucleocapsid (N) protein interaction affinity increased, leading to enhanced oligomerization of the N protein; (2) one of the identified SUMOylation sites, K65, is critical for its nuclear translocation. These results suggest that the host human SUMOylation pathway may be critical for N protein functions in viral replication and pathology in vivo. Thus, blocking essential host pathways could provide a novel strategy for future anti-viral therapeutics development, such as for SARS-CoV-2 and other viruses. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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15 pages, 1040 KiB

Open AccessArticle

A Sequential Cross-Sectional Analysis Producing Robust Weekly COVID-19 Rates for South East Asian Countries

by Amani Almohaimeed and Jochen Einbeck

Viruses 2023, 15(7), 1572; https://doi.org/10.3390/v15071572 - 18 Jul 2023

Viewed by 1350

Abstract

The COVID-19 pandemic has expanded fast over the world, affecting millions of people and generating serious health, social, and economic consequences. All South East Asian countries have experienced the pandemic, with various degrees of intensity and response. As the pandemic progresses, it is [...] Read more.

The COVID-19 pandemic has expanded fast over the world, affecting millions of people and generating serious health, social, and economic consequences. All South East Asian countries have experienced the pandemic, with various degrees of intensity and response. As the pandemic progresses, it is important to track and analyse disease trends and patterns to guide public health policy and treatments. In this paper, we carry out a sequential cross-sectional study to produce reliable weekly COVID-19 death (out of cases) rates for South East Asian countries for the calendar years 2020, 2021, and 2022. The main objectives of this study are to characterise the trends and patterns of COVID-19 death rates in South East Asian countries through time, as well as compare COVID-19 rates among countries and regions in South East Asia. Our raw data are (daily) case and death counts acquired from “Our World in Data”, which, however, for some countries and time periods, suffer from sparsity (zero or small counts), and therefore require a modelling approach where information is adaptively borrowed from the overall dataset where required. Therefore, a sequential cross-sectional design will be utilised, that will involve examining the data week by week, across all countries. Methodologically, this is achieved through a two-stage random effect shrinkage approach, with estimation facilitated by nonparametric maximum likelihood. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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12 pages, 1324 KiB

Open AccessReview

Harnessing Antiviral Peptides as Means for SARS-CoV-2 Control

by Khatereh Zarkesh, Mohsen Akbarian, Lobat Tayebi, Vladimir N. Uversky, Alberto Rubio-Casillas and Elrashdy M. Redwan

COVID 2023, 3(7), 975-986; https://doi.org/10.3390/covid3070070 - 29 Jun 2023

Cited by 1 | Viewed by 2103

Abstract

Several times during the past two decades, epidemic viral diseases created global challenges. Although many solutions have been proposed to deal with this tight spot, it is still believed that public vaccination represents the most effective strategy to handle it. So far, various [...] Read more.

Several times during the past two decades, epidemic viral diseases created global challenges. Although many solutions have been proposed to deal with this tight spot, it is still believed that public vaccination represents the most effective strategy to handle it. So far, various kinds of vaccines including protein subunits, virus-like particles, inactivated, live attenuated, viral vectors, RNA, and DNA vaccines have been used in the prevention of COVID-19. Among the various categories of vaccines, peptide vaccines have created a new hope for quick and trustworthy access due to the development of proteomics equipment. This review specifically focuses on vaccines and peptide therapies in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We consider here the efficacy and safety of subunit and synthetic peptides vaccine in clinical trial phases. Furthermore, monoclonal antibodies with the ability to suppress the development of SARS-CoV-2, those candidates that have entered into clinical trials until March 2023, were selected and evaluated. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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13 pages, 4243 KiB

Open AccessArticle

RDE Treatment Prevents Non-Specific Detection of SARS-CoV-2- and Influenza-Specific IgG Antibodies in Heat-Inactivated Serum Samples

by Arina Goshina, Victoria Matyushenko, Daria Mezhenskaya, Alexandra Rak, Anastasia Katelnikova, Denis Gusev, Larisa Rudenko and Irina Isakova-Sivak

Antibodies 2023, 12(2), 39; https://doi.org/10.3390/antib12020039 - 16 Jun 2023

Viewed by 3227

Abstract

Assessing the levels of serum IgG antibodies is widely used to measure immunity to influenza and the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after natural infection or vaccination with specific vaccines, as well as to study immune responses to these viruses [...] Read more.

Assessing the levels of serum IgG antibodies is widely used to measure immunity to influenza and the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after natural infection or vaccination with specific vaccines, as well as to study immune responses to these viruses in animal models. For safety reasons, sometimes serum specimens collected from infected individuals are subjected to heat inactivation at 56 °C to reduce the risk of infecting personnel during serological studies. However, this procedure may affect the level of virus-specific antibodies, making the results of antibody immunoassays uninterpretable. Here, we evaluated the effect of the heat inactivation of human, ferret and hamster serum samples on the binding of IgG antibodies to the influenza and SARS-CoV-2 antigens. For this, serum samples of naive and immune hosts were analyzed in three variants: (i) untreated sera, (ii) heated at 56 °C for 1 h, and (iii) treated with receptor-destroying enzyme (RDE). The samples were studied through an in-house enzyme-linked immunosorbent assay (ELISA) using whole influenza virus or recombinant proteins corresponding to nucleocapsid (N) protein and the receptor-binding domain of SARS-CoV-2 Spike (RBD) as antigens. We demonstrated that the heat inactivation of the naive serum samples of various hosts can lead to false-positive results, while RDE treatment abolished the effect of the non-specific binding of IgG antibodies to the viral antigens. Furthermore, RDE also significantly decreased the level of virus-specific IgG antibodies in SARS-CoV-2 and influenza-immune sera of humans and animals, although it is unknown whether it actually removes true virus-specific IgG antibodies or only non-specifically binding artifacts. Nevertheless, we suggest that the RDE treatment of human and animal sera may be useful in preventing false-positive results in various immunoassays, while also neutralizing infectious virus, since the standard protocol for the use of RDE also includes heating the sample at 56 °C. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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15 pages, 948 KiB

Open AccessArticle

Persistence of SARS-CoV-2 IgG Antibody Response among South African Adults: A Prospective Cohort Study

by Oladele Vincent Adeniyi, Oyewole Christopher Durojaiye and Charity Masilela

Vaccines 2023, 11(6), 1068; https://doi.org/10.3390/vaccines11061068 - 6 Jun 2023

Cited by 2 | Viewed by 2609

Abstract

This study assesses the durability of severe acute respiratory coronavirus-2 (SARS-CoV-2) anti-nucleocapsid (anti-N) immunoglobulin G (IgG) after infection and examines its association with established risk factors among South African healthcare workers (HCWs). Blood samples were obtained from 390 HCWs with diagnosis of coronavirus [...] Read more.

This study assesses the durability of severe acute respiratory coronavirus-2 (SARS-CoV-2) anti-nucleocapsid (anti-N) immunoglobulin G (IgG) after infection and examines its association with established risk factors among South African healthcare workers (HCWs). Blood samples were obtained from 390 HCWs with diagnosis of coronavirus disease 2019 (COVID-19) for assay of the SARS-CoV-2 anti-N IgG at two time points (Phase 1 and 2) between November 2020 and February 2021. Out of 390 HCWs with a COVID-19 diagnosis, 267 (68.5%) had detectable SARS-CoV-2 anti-N IgG antibodies at the end of Phase I. These antibodies persisted for 4–5 and 6–7 months in 76.4% and 16.1%, respectively. In the multivariate logistic regression model analysis, Black participants were more likely to sustain SARS-CoV-2 anti-N IgG for 4–5 months. However, participants who were HIV positive were less likely to sustain SARS-CoV-2 anti-N IgG antibodies for 4–5 months. In addition, individuals who were <45 years of age were more likely to sustain SARS-CoV-2 anti-N IgG for 6–7 months. Of the 202 HCWs selected for Phase 2, 116 participants (57.4%) had persistent SARS-CoV-2 anti-N IgG for an extended mean period of 223 days (7.5 months). Findings support the longevity of vaccine responses against SARS-CoV-2 in Black Africans. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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15 pages, 1155 KiB

Open AccessReview

Implications of COVID-19 Pandemic on Pregnancy: Current Status and Controversies

by Grace C. Greenberg, Nandini Vishwakarma, Myna Prakash Tirupattur, Hannah M. Sprague and Laxmansa C. Katwa

COVID 2023, 3(6), 859-873; https://doi.org/10.3390/covid3060062 - 26 May 2023

Cited by 2 | Viewed by 5600

Abstract

The COVID-19 pandemic unnerved the global population in 2019 and has continued to evolve ever since. Throughout this time, investigations concerning the health of the groups most susceptible to this virus, including the elderly, those with compromised immunity or chronic diseases, and pregnant [...] Read more.

The COVID-19 pandemic unnerved the global population in 2019 and has continued to evolve ever since. Throughout this time, investigations concerning the health of the groups most susceptible to this virus, including the elderly, those with compromised immunity or chronic diseases, and pregnant women, have taken place. Numerous articles have been formulated on the effects of COVID-19 infection on maternal, fetal, and neonatal health, but there are many controversies that still exist within the current literature. Even three years later, it is not fully understood how a maternal infection or vaccination of COVID-19 can impact pregnancy and the fetus, and these topics require further investigation and conclusive results. The aim of this article is to explain the risks for a mother and the neonate, during and after pregnancy, with the emergence of the COVID-19 pandemic. Additionally, this report presents the current state of the literature on whether vaccination during pregnancy is more beneficial or harmful. Finally, this review examines studies regarding the exacerbation of the effects of COVID-19 on pregnancies in various organ systems, particularly the cardiovascular system, in relevance to pre-existing and emerging conditions and the ethnicity of the mother. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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27 pages, 5932 KiB

Open AccessArticle

Both Feline Coronavirus Serotypes 1 and 2 Infected Domestic Cats Develop Cross-Reactive Antibodies to SARS-CoV-2 Receptor Binding Domain: Its Implication to Pan-CoV Vaccine Development

by Janet K. Yamamoto, Lekshmi K. Edison, Dawne K. Rowe-Haas, Tomomi Takano, Chen Gilor, Chiquitha D. Crews, Apichai Tuanyok, Ananta P. Arukha, Sayaka Shiomitsu, Heather D. S. Walden, Tsutomu Hohdatsu, Stephen M. Tompkins, John G. Morris Jr., Bikash Sahay and Subhashinie Kariyawasam

Viruses 2023, 15(4), 914; https://doi.org/10.3390/v15040914 - 31 Mar 2023

Cited by 9 | Viewed by 4975

Abstract

The current study was initiated when our specific-pathogen-free laboratory toms developed unexpectedly high levels of cross-reactive antibodies to human SARS-CoV-2 (SCoV2) receptor binding domain (RBD) upon mating with feline coronavirus (FCoV)-positive queens. Multi-sequence alignment analyses of SCoV2 Wuhan RBD and four strains each [...] Read more.

The current study was initiated when our specific-pathogen-free laboratory toms developed unexpectedly high levels of cross-reactive antibodies to human SARS-CoV-2 (SCoV2) receptor binding domain (RBD) upon mating with feline coronavirus (FCoV)-positive queens. Multi-sequence alignment analyses of SCoV2 Wuhan RBD and four strains each from FCoV serotypes 1 and 2 (FCoV1 and FCoV2) demonstrated an amino acid sequence identity of 11.5% and a similarity of 31.8% with FCoV1 RBD (12.2% identity and 36.5% similarity for FCoV2 RBD). The sera from toms and queens cross-reacted with SCoV2 RBD and reacted with FCoV1 RBD and FCoV2 spike-2, nucleocapsid, and membrane proteins, but not with FCoV2 RBD. Thus, the queens and toms were infected with FCoV1. Additionally, the plasma from six FCoV2-inoculated cats reacted with FCoV2 and SCoV2 RBDs, but not with FCoV1 RBD. Hence, the sera from both FCoV1-infected cats and FCoV2-infected cats developed cross-reactive antibodies to SCoV2 RBD. Furthermore, eight group-housed laboratory cats had a range of serum cross-reactivity to SCoV2 RBD even 15 months later. Such cross-reactivity was also observed in FCoV1-positive group-housed pet cats. The SCoV2 RBD at a high non-toxic dose and FCoV2 RBD at a 60–400-fold lower dose blocked the in vitro FCoV2 infection, demonstrating their close structural conformations essential as vaccine immunogens. Remarkably, such cross-reactivity was also detected by the peripheral blood mononuclear cells of FCoV1-infected cats. The broad cross-reactivity between human and feline RBDs provides essential insights into developing a pan-CoV vaccine. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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12 pages, 248 KiB

Open AccessSystematic Review

Impact of COVID-19 Vaccination on Pregnant Women

by Ishaan Chaubey, Harini Vijay, Sakthivel Govindaraj, Hemalatha Babu, Narayanaiah Cheedarla, Esaki M. Shankar, Ramachandran Vignesh and Vijayakumar Velu

Pathogens 2023, 12(3), 431; https://doi.org/10.3390/pathogens12030431 - 9 Mar 2023

Cited by 7 | Viewed by 3289

Abstract

In light of the COVID-19 pandemic, researchers across the world hastened to develop vaccines that would aid in bolstering herd immunity. Utilizing mRNA coding and viral vector technology, the currently approved vaccines were required to undergo extensive testing to confirm their safety for [...] Read more.

In light of the COVID-19 pandemic, researchers across the world hastened to develop vaccines that would aid in bolstering herd immunity. Utilizing mRNA coding and viral vector technology, the currently approved vaccines were required to undergo extensive testing to confirm their safety for mass usage in the general population. However, clinical trials failed to test the safety and efficacy of the COVID-19 vaccines in groups with weakened immune systems, especially pregnant women. Lack of information on the effects of vaccinations in pregnancy and the safety of fetuses are among the topmost reasons preventing pregnant women from receiving immunization. Thus, the lack of data examining the effects of COVID-19 vaccinations on pregnant women must be addressed. This review focused on the safety and efficacy of the approved COVID-19 vaccinations in pregnancy and their impact on both maternal and fetal immune responses. For that, we took the approach of combined systematic review/meta-analysis and compiled the available data from the original literature from PubMed, Web of Science, EMBASE and Medline databases. All articles analyzed presented no adverse effects of vaccination in pregnancy, with varying conclusions on the degree of effectiveness. The majority of the findings described robust immune responses in vaccinated pregnant women, successful transplacental antibody transfer, and implications for neonatal immunity. Hence, findings from the cumulative data available can be helpful in achieving COVID-19 herd immunization, including pregnant women. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

15 pages, 1296 KiB

Open AccessArticle

Human Genome Polymorphisms and Computational Intelligence Approach Revealed a Complex Genomic Signature for COVID-19 Severity in Brazilian Patients

by André Filipe Pastor, Cássia Docena, Antônio Mauro Rezende, Flávio Rosendo da Silva Oliveira, Marília de Albuquerque Sena, Clarice Neuenschwander Lins de Morais, Cristiane Campello Bresani-Salvi, Luydson Richardson Silva Vasconcelos, Kennya Danielle Campelo Valença, Carolline de Araújo Mariz, Carlos Brito, Cláudio Duarte Fonseca, Cynthia Braga, Christian Robson de Souza Reis, Ernesto Torres de Azevedo Marques and Bartolomeu Acioli-Santos

Viruses 2023, 15(3), 645; https://doi.org/10.3390/v15030645 - 28 Feb 2023

Cited by 3 | Viewed by 2513

Abstract

We present a genome polymorphisms/machine learning approach for severe COVID-19 prognosis. Ninety-six Brazilian severe COVID-19 patients and controls were genotyped for 296 innate immunity loci. Our model used a feature selection algorithm, namely recursive feature elimination coupled with a support vector machine, to [...] Read more.

We present a genome polymorphisms/machine learning approach for severe COVID-19 prognosis. Ninety-six Brazilian severe COVID-19 patients and controls were genotyped for 296 innate immunity loci. Our model used a feature selection algorithm, namely recursive feature elimination coupled with a support vector machine, to find the optimal loci classification subset, followed by a support vector machine with the linear kernel (SVM-LK) to classify patients into the severe COVID-19 group. The best features that were selected by the SVM-RFE method included 12 SNPs in 12 genes: PD-L1, PD-L2, IL10RA, JAK2, STAT1, IFIT1, IFIH1, DC-SIGNR, IFNB1, IRAK4, IRF1, and IL10. During the COVID-19 prognosis step by SVM-LK, the metrics were: 85% accuracy, 80% sensitivity, and 90% specificity. In comparison, univariate analysis under the 12 selected SNPs showed some highlights for individual variant alleles that represented risk (PD-L1 and IFIT1) or protection (JAK2 and IFIH1). Variant genotypes carrying risk effects were represented by PD-L2 and IFIT1 genes. The proposed complex classification method can be used to identify individuals who are at a high risk of developing severe COVID-19 outcomes even in uninfected conditions, which is a disruptive concept in COVID-19 prognosis. Our results suggest that the genetic context is an important factor in the development of severe COVID-19. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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18 pages, 2456 KiB

Open AccessArticle

Assessment of the Biological Impact of SARS-CoV-2 Genetic Variation Using an Authentic Virus Neutralisation Assay with Convalescent Plasma, Vaccinee Sera, and Standard Reagents

by Naomi S. Coombes, Kevin R. Bewley, Yann Le Duff, Matthew Hurley, Lauren J. Smith, Thomas M. Weldon, Karen Osman, Steven Pullan, Neil Berry, Bassam Hallis, Sue Charlton, Yper Hall and Simon G. P. Funnell

Viruses 2023, 15(3), 633; https://doi.org/10.3390/v15030633 - 25 Feb 2023

Cited by 2 | Viewed by 2974

Abstract

In the summer of 2020, it became clear that the genetic composition of SARS-CoV-2 was changing rapidly. This was highlighted by the rapid emergence of the D614G mutation at that time. In the autumn of 2020, the project entitled “Agility” was initiated with [...] Read more.

In the summer of 2020, it became clear that the genetic composition of SARS-CoV-2 was changing rapidly. This was highlighted by the rapid emergence of the D614G mutation at that time. In the autumn of 2020, the project entitled “Agility” was initiated with funding from the Coalition for Epidemic Preparedness Innovations (CEPI) to assess new variants of SARS-CoV-2. The project was designed to reach out and intercept swabs containing live variant viruses in order to generate highly characterised master and working stocks, and to assess the biological consequences of the rapid genetic changes using both in vitro and in vivo approaches. Since November 2020, a total of 21 variants have been acquired and tested against either a panel of convalescent sera from early in the pandemic, and/or a panel of plasma from triple-vaccinated participants. A pattern of continuous evolution of SARS-CoV-2 has been revealed. Sequential characterisation of the most globally significant variants available to us, generated in real-time, indicated that the most recent Omicron variants appear to have evolved in a manner that avoids immunological recognition by convalescent plasma from the era of the ancestral virus when analysed in an authentic virus neutralisation assay. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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15 pages, 981 KiB

Open AccessReview

Employing T-Cell Memory to Effectively Target SARS-CoV-2

by Zaw Htet Tun, Nang Thinn Thinn Htike, Chaw Kyi-Tha-Thu and Wing-Hin Lee

Pathogens 2023, 12(2), 301; https://doi.org/10.3390/pathogens12020301 - 11 Feb 2023

Viewed by 2693

Abstract

Well-trained T-cell immunity is needed for early viral containment, especially with the help of an ideal vaccine. Although most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected convalescent cases have recovered with the generation of virus-specific memory T cells, some cases have encountered T-cell [...] Read more.

Well-trained T-cell immunity is needed for early viral containment, especially with the help of an ideal vaccine. Although most severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected convalescent cases have recovered with the generation of virus-specific memory T cells, some cases have encountered T-cell abnormalities. The emergence of several mutant strains has even threatened the effectiveness of the T-cell immunity that was established with the first-generation vaccines. Currently, the development of next-generation vaccines involves trying several approaches to educate T-cell memory to trigger a broad and fast response that targets several viral proteins. As the shaping of T-cell immunity in its fast and efficient form becomes important, this review discusses several interesting vaccine approaches to effectively employ T-cell memory for efficient viral containment. In addition, some essential facts and future possible consequences of using current vaccines are also highlighted. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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14 pages, 3913 KiB

Open AccessArticle

SARS-CoV-2 Omicron BA.4/BA.5 Mutations in Spike Leading to T Cell Escape in Recently Vaccinated Individuals

by Maarten E. Emmelot, Martijn Vos, Mardi C. Boer, Nynke Y. Rots, Cécile A. C. M. van Els and Patricia Kaaijk

Viruses 2023, 15(1), 101; https://doi.org/10.3390/v15010101 - 29 Dec 2022

Cited by 12 | Viewed by 5876

Abstract

SARS-CoV-2 Omicron (B.1.1.529) lineages rapidly became dominant in various countries reflecting its enhanced transmissibility and ability to escape neutralizing antibodies. Although T cells induced by ancestral SARS-CoV-2-based vaccines also recognize Omicron variants, we showed in our previous study that there was a marked [...] Read more.

SARS-CoV-2 Omicron (B.1.1.529) lineages rapidly became dominant in various countries reflecting its enhanced transmissibility and ability to escape neutralizing antibodies. Although T cells induced by ancestral SARS-CoV-2-based vaccines also recognize Omicron variants, we showed in our previous study that there was a marked loss of T cell cross-reactivity to spike epitopes harboring Omicron BA.1 mutations. The emerging BA.4/BA.5 subvariants carry other spike mutations than the BA.1 variant. The present study aims to investigate the impact of BA.4/BA.5 spike mutations on T cell cross-reactivity at the epitope level. Here, we focused on universal T-helper epitopes predicted to be presented by multiple common HLA class II molecules for broad population coverage. Fifteen universal T-helper epitopes of ancestral spike, which contain mutations in the Omicron BA.4/BA.5 variants, were identified utilizing a bioinformatic tool. T cells isolated from 10 subjects, who were recently vaccinated with mRNA-based BNT162b2, were tested for functional cross-reactivity between epitopes of ancestral SARS-CoV-2 spike and the Omicron BA.4/BA.5 spike counterparts. Reduced T cell cross-reactivity in one or more vaccinees was observed against 87% of the tested 15 non-conserved CD4⁺ T cell epitopes. These results should be considered for vaccine boosting strategies to protect against Omicron BA.4/BA.5 and future SARS-CoV-2 variants. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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12 pages, 2175 KiB

Open AccessArticle

Kinetics of Immune Subsets in COVID-19 Patients Treated with Corticosteroids

by Apostolos Georgios Pappas, Anna-Louiza Chaliasou, Andreas Panagopoulos, Konstantina Dede, Stavroula Daskalopoulou, Evie Moniem, Eftychia Polydora, Eirini Grigoriou, Katherina Psarra, Alexandra Tsirogianni and Ioannis Kalomenidis

Viruses 2023, 15(1), 51; https://doi.org/10.3390/v15010051 - 24 Dec 2022

Cited by 6 | Viewed by 2713

Abstract

Rationale: Changes in anti-SARS-CoV-2 defense immune subsets in patients treated with dexamethasone (DXM) for severe COVID-19 and their relation to disease outcomes are poorly understood. Methods: Blood-lymphocyte subsets of 110 hospitalized COVID-19 patients were prospectively examined. A first sample was taken at enrollment [...] Read more.

Rationale: Changes in anti-SARS-CoV-2 defense immune subsets in patients treated with dexamethasone (DXM) for severe COVID-19 and their relation to disease outcomes are poorly understood. Methods: Blood-lymphocyte subsets of 110 hospitalized COVID-19 patients were prospectively examined. A first sample was taken at enrollment and a second one 7–10 days later. Total B-, T-lymphocytes, CD4+, CD8+, T-regulatory (Treg), Natural-Killer (NK) and NK T-cells were counted using flow cytometry. Results: At enrollment, patients with respiratory failure, characterized by DXM failure (intubation/death) or DXM success (hospital discharge) exhibited significantly fewer CD3+, CD4+ and CD8+ cells and B-lymphocytes compared to the control group (no respiratory failure/no DXM). At the time of treatment completion, the DXM-failure group exhibited significantly fewer CD3+, CD4+ and CD8+ cells, memory CD4+ and CD8+ T-lymphocytes, compared to the control and the DXM-success groups and fewer activated CD4+ T-lymphocytes, Tregs and NK cells compared to the control group. At the time of treatment completion, the number of all investigated lymphocyte subsets increased in the DXM-success group and was similar to those of the control group. NK cells significantly decreased over time in the DXM-failure group. Conclusion: The lymphocyte kinetics differ between DXM-treated and control COVID-19 patients and are associated with clinical outcomes. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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14 pages, 1728 KiB

Open AccessArticle

Antibodies Induced by Homologous or Heterologous Inactivated (CoronaVac/BBIBP-CorV) and Recombinant Protein Subunit Vaccines (ZF2001) Dramatically Enhanced Inhibitory Abilities against B.1.351, B.1.617.2, and B.1.1.529 Variants

by Xuesong Xu, Yi Hong, Erjing Chen, Yaping Wang, Biao Ma, Jiali Li, Wei Su, Yuxin Zhou and Mingzhou Zhang

Vaccines 2022, 10(12), 2110; https://doi.org/10.3390/vaccines10122110 - 9 Dec 2022

Cited by 4 | Viewed by 1914

Abstract

Safe and effective vaccines for Corona Virus Disease 2019 (COVID-19) can prevent the virus from infecting human populations and treat patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we discuss the inhibitory abilities of primary and booster vaccine-induced [...] Read more.

Safe and effective vaccines for Corona Virus Disease 2019 (COVID-19) can prevent the virus from infecting human populations and treat patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we discuss the inhibitory abilities of primary and booster vaccine-induced antibodies inhibitory ability toward the SARS-CoV-2 wild-type strain, as well as B.1.1.7, B.1.351, P.1, B.1.617.2, and B.1.1.529. We confirmed these antibodies had the strongest inhibitory effects on the wild-type strain and cross-inhibition activities against other mutant strains after two inactivated vaccine doses. However, the B.1.351, B.1.617.2 and B.1.1.529 mutants exhibit antibody resistance in the vaccine serum. Antibodies induced by homologous inactivated vaccines (n = 92) presented more effective inhibition against tested SARS-CoV-2 strains (p < 0.0001), especially B.1.351, B.1.617.2, and B.1.1.529 mutant strains, which had strong immune escape characteristics. In addition, a heterologous booster vaccination (n = 50) of a protein subunit vaccine ZifiVax (ZF2001) significantly restored humoral immune responses and even showed an increasing response against wild-type, B.1.351, B.1.617.2, and B.1.1.529 than homologous inactivated vaccines. Our analysis of the humoral immune response elicited by the different vaccine regimens, including inhibiting antibodies, indicated that a booster, whether homologous or heterologous, could be essential for achieving greater efficacy against SARS-CoV-2. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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10 pages, 417 KiB

Open AccessCommunication

Antibodies to Commonly Circulating Viral Pathogens Modulate Serological Response to Severe Acute Respiratory Syndrome Coronavirus 2 Infection

by Protim Sarker, Evana Akhtar, Sharmin Akter, Sultana Rajia, Rakib Ullah Kuddusi, Razu Ahmed, Md. Jakarea, Mohammad Zahirul Islam, Dewan Md Emdadul Hoque, Shehlina Ahmed and Rubhana Raqib

COVID 2022, 2(12), 1625-1634; https://doi.org/10.3390/covid2120117 - 23 Nov 2022

Cited by 1 | Viewed by 2087

Abstract

The purpose of this study was to determine the seropositivity of circulating viral pathogens and their association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity. In a cross-sectional design, inhabitants (aged 10–60 years) of the slum and surrounding non-slum areas of Dhaka [...] Read more.

The purpose of this study was to determine the seropositivity of circulating viral pathogens and their association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity. In a cross-sectional design, inhabitants (aged 10–60 years) of the slum and surrounding non-slum areas of Dhaka and Chattogram Metropolitan cities in Bangladesh were enrolled from October 2020 to February 2021. Antibodies to SARS-CoV-2, influenza B, parainfluenza, respiratory syncytial virus (RSV), human coronavirus HKU1 (HCoV-HKU1), dengue and chikungunya viruses were determined in plasma. The association of SARS-CoV-2 seropositivity with seropositivity to other viruses was assessed using the multi-variate logistic regression model. Seroprevalence of SARS-CoV-2, influenza B, RSV, dengue, chikungunya, HCoV-HKU1 and the parainfluenza virus were 68.3%, 98%, 50.0%, 16.5%, 15.5%, 3.36% and 0.0%, respectively. Individuals seropositive for RSV had lower odds (OR = 0.60; 95% CI= 0.49, 0.73) of SARS-CoV-2 seropositivity compared to RSV-seronegative individuals. Conversely, higher odds of SARS-CoV-2 seropositivity were observed in participants seropositive for dengue (OR= 1.73; 95% CI = 1.14, 2.66, only in slum) or chikungunya (OR = 1.48; 95% CI = 1.11, 1.95) compared to their seronegative counterparts. The study findings indicated that exposure to vector-borne virus dengue or chikungunya enhance, while antibodies to respiratory virus RSV decrease, the serological response to SARS-CoV-2. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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11 pages, 1919 KiB

Open AccessArticle

Expression and Purification of Recombinant SARS-CoV-2 Accessory Protein ORF7a and Functional Analysis of Its Role in Up-Regulating Cytokine Production

by Dan Chen, Zhenhua Zheng and Zhenggang Han

COVID 2022, 2(10), 1449-1459; https://doi.org/10.3390/covid2100104 - 12 Oct 2022

Viewed by 2391

Abstract

The severity of coronavirus disease 2019 is closely linked to dysregulated immune responses. The search for viral proteins associated with immune regulation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to reveal the pathogenicity of the virus. In this study, accessory [...] Read more.

The severity of coronavirus disease 2019 is closely linked to dysregulated immune responses. The search for viral proteins associated with immune regulation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to reveal the pathogenicity of the virus. In this study, accessory proteins ORF7a (referred to as ORF7a-1 and ORF7a-2, respectively) from two SARS-related coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2, were produced through the denaturing and refolding of inclusion body proteins. The recombinant protein was incubated with alveolar epithelial cells, and the transcription and expression levels of major cytokines were determined by reverse transcription-quantitative PCR and enzyme-linked immunosorbent assay. SARS-related coronavirus ORF7a can up-regulate the transcription and expression of interleukin-6, C-C motif chemokine ligand 8, interferon α, and interferon β. The results also indicated that the two highly conserved ORF7a had certain differences in promoting the transcription and expression of cytokines. The study showed that ORF7a is a virus-encoded immune regulator by alveolar epithelial cells that plays an important role in the pathogenicity of SARS-related coronaviruses. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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13 pages, 2187 KiB

Open AccessEditor’s ChoiceArticle

In Vitro and In Vivo Characterization of a Broadly Neutralizing Anti-SARS-CoV-2 Antibody Isolated from a Semi-Immune Phage Display Library

by Edith González-González, Gregorio Carballo-Uicab, Juana Salinas-Trujano, María I. Cortés-Paniagua, Said Vázquez-Leyva, Luis Vallejo-Castillo, Ivette Mendoza-Salazar, Keyla Gómez-Castellano, Sonia M. Pérez-Tapia and Juan C. Almagro

Antibodies 2022, 11(3), 57; https://doi.org/10.3390/antib11030057 - 6 Sep 2022

Cited by 5 | Viewed by 3468

Abstract

Neutralizing antibodies targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and/or treat COVID-19. However, as SARS-CoV-2 has evolved into new variants, most of the neutralizing antibodies authorized by the US FDA and/or EMA to treat COVID-19 [...] Read more.

Neutralizing antibodies targeting the receptor-binding domain (RBD) of SARS-CoV-2 are among the most promising strategies to prevent and/or treat COVID-19. However, as SARS-CoV-2 has evolved into new variants, most of the neutralizing antibodies authorized by the US FDA and/or EMA to treat COVID-19 have shown reduced efficacy or have failed to neutralize the variants of concern (VOCs), particularly B.1.1.529 (Omicron). Previously, we reported the discovery and characterization of antibodies with high affinity for SARS-CoV-2 RBD Wuhan (WT), B.1.617.2 (Delta), and B.1.1.529 (Omicron) strains. One of the antibodies, called IgG-A7, also blocked the interaction of human angiotensin-converting enzyme 2 (hACE2) with the RBDs of the three strains, suggesting it may be a broadly SARS-CoV-2 neutralizing antibody. Herein, we show that IgG-A7 efficiently neutralizes all the three SARS-CoV-2 strains in plaque reduction neutralization tests (PRNTs). In addition, we demonstrate that IgG-A7 fully protects K18-hACE2 transgenic mice infected with SARS-CoV-2 WT. Taken together, our findings indicate that IgG-A7 could be a suitable candidate for development of antibody-based drugs to treat and/or prevent SARS-CoV-2 VOCs infection. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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15 pages, 2256 KiB

Open AccessArticle

A Novel Single-Stranded RNA-Based Adjuvant Improves the Immunogenicity of the SARS-CoV-2 Recombinant Protein Vaccine

by Dong Liu, Chaoqiang An, Yu Bai, Kelei Li, Jianyang Liu, Qian Wang, Qian He, Ziyang Song, Jialu Zhang, Lifang Song, Bopei Cui, Qunying Mao, Wei Jiang and Zhenglun Liang

Viruses 2022, 14(9), 1854; https://doi.org/10.3390/v14091854 - 24 Aug 2022

Cited by 5 | Viewed by 2744

Abstract

The research and development (R&D) of novel adjuvants is an effective measure for improving the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant protein vaccine. Toward this end, we designed a novel single-stranded RNA-based adjuvant, L2, from the SARS-CoV-2 prototype [...] Read more.

The research and development (R&D) of novel adjuvants is an effective measure for improving the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant protein vaccine. Toward this end, we designed a novel single-stranded RNA-based adjuvant, L2, from the SARS-CoV-2 prototype genome. L2 could initiate retinoic acid-inducible gene-I signaling pathways to effectively activate the innate immunity. ZF2001, an aluminum hydroxide (Al) adjuvanted SARS-CoV-2 recombinant receptor binding domain (RBD) subunit vaccine with emergency use authorization in China, was used for comparison. L2, with adjuvant compatibility with RBD, elevated the antibody response to a level more than that achieved with Al, CpG 7909, or poly(I:C) as adjuvants in mice. L2 plus Al with composite adjuvant compatibility with RBD markedly improved the immunogenicity of ZF2001; in particular, neutralizing antibody titers increased by about 44-fold for Omicron, and the combination also induced higher levels of antibodies than CpG 7909/poly(I:C) plus Al in mice. Moreover, L2 and L2 plus Al effectively improved the Th1 immune response, rather than the Th2 immune response. Taken together, L2, used as an adjuvant, enhanced the immune response of the SARS-CoV-2 recombinant RBD protein vaccine in mice. These findings should provide a basis for the R&D of novel RNA-based adjuvants. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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8 pages, 630 KiB

Open AccessBrief Report

Time-of-Day Variation in SARS-CoV-2 RNA Levels during the Second Wave of COVID-19

by Xiaodong Zhuang, Wei Wang, Helene Borrmann, Peter Balfe, Philippa C. Matthews, David W. Eyre, Elizabeth B. Klerman and Jane A. McKeating

Viruses 2022, 14(8), 1728; https://doi.org/10.3390/v14081728 - 5 Aug 2022

Cited by 3 | Viewed by 2595

Abstract

Circadian rhythms influence and coordinate an organism’s response to its environment and to invading pathogens. We studied the diurnal variation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in nasal/throat swabs collected in late 2020 to spring 2021 in a population immunologically [...] Read more.

Circadian rhythms influence and coordinate an organism’s response to its environment and to invading pathogens. We studied the diurnal variation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in nasal/throat swabs collected in late 2020 to spring 2021 in a population immunologically naïve to SARS-CoV-2 and prior to widespread vaccination. SARS-CoV-2 diagnostic PCR data from 1698 participants showed a significantly higher viral load in samples obtained in the afternoon, in males, and in hospitalised patients when linear mixed modelling was applied. This study illustrates the importance of recording sample collection times when measuring viral replication parameters in clinical and research studies. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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14 pages, 1084 KiB

Open AccessArticle

DNA-Vaccine-Induced Immune Response Correlates with Lower Viral SARS-CoV-2 Titers in a Ferret Model

by Mirco Compagnone, Eleonora Pinto, Erika Salvatori, Lucia Lione, Antonella Conforti, Silvia Marchese, Micol Ravà, Kathryn Ryan, Yper Hall, Emma Rayner, Francisco J. Salguero, Jemma Paterson, Matteo Iannacone, Raffaele De Francesco, Luigi Aurisicchio and Fabio Palombo

Vaccines 2022, 10(8), 1178; https://doi.org/10.3390/vaccines10081178 - 25 Jul 2022

Cited by 3 | Viewed by 2949

Abstract

The COVID-19 pandemic is entering a new era with the approval of many SARS-CoV-2 vaccines. In spite of the restoration of an almost normal way of life thanks to the immune protection elicited by these innovative vaccines, we are still facing high viral [...] Read more.

The COVID-19 pandemic is entering a new era with the approval of many SARS-CoV-2 vaccines. In spite of the restoration of an almost normal way of life thanks to the immune protection elicited by these innovative vaccines, we are still facing high viral circulation, with a significant number of deaths. To further explore alternative vaccination platforms, we developed COVID-eVax—a genetic vaccine based on plasmid DNA encoding the RBD domain of the SARS-CoV-2 spike protein. Here, we describe the correlation between immune responses and the evolution of viral infection in ferrets infected with the live virus. We demonstrate COVID-eVax immunogenicity as means of antibody response and, above all, a significant T-cell response, thus proving the critical role of T-cell immunity, in addition to the neutralizing antibody activity, in controlling viral spread. Full article

(This article belongs to the Topic Host Response against SARS-CoV-2 Infection: Implications for Diagnosis, Treatment and Vaccine Development)

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