Vaccines

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13 pages, 2723 KiB

Open AccessArticle

Stabilizing Prefusion SARS-CoV-2 Spike by Destabilizing the Postfusion Conformation

by Debajyoti Chakraborty, Randhir Singh, Raju S. Rajmani, Sahil Kumar, Rajesh P. Ringe and Raghavan Varadarajan

Vaccines 2025, 13(3), 315; https://doi.org/10.3390/vaccines13030315 - 14 Mar 2025

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Abstract

Background/Objectives: As with many viral fusion proteins, the native conformation of SARS-CoV-2 Spike is metastable. Most COVID-19 vaccines utilize a stabilized Spike (Spike-2P) containing two proline substitutions, and subsequently, a further stabilized variant with four additional proline substitutions, Spike-6P, has been developed. In [...] Read more.

Background/Objectives: As with many viral fusion proteins, the native conformation of SARS-CoV-2 Spike is metastable. Most COVID-19 vaccines utilize a stabilized Spike (Spike-2P) containing two proline substitutions, and subsequently, a further stabilized variant with four additional proline substitutions, Spike-6P, has been developed. In an alternative approach, we introduced two aspartic acid residues (2D) in the HR1 region of Spike at positions that are exposed and buried in the pre- and postfusion states, respectively, to destabilize the postfusion conformation. Methods: The recombinant protein constructs were expressed in a mammalian cell culture and characterized for their yield and antigenicity, and the formulations were then used to immunize hamsters. After two immunizations, the hamsters were challenged with live B.1.351 SARS-CoV-2 virus for an evaluation of the protective efficacy. Results: The introduction of the two aspartic acid mutations resulted in an approximately six-fold increase in expression, comparable to that in Spike-2P. When the 2D mutations were combined with the above four proline mutations (Spike-4P-2D), this led to a further three- to four-fold enhancement of protein expression, similar to that seen in Spike-6P. When formulated with the oil-in-water emulsion adjuvant Sepivac SWE, the 2P, 2D, 6P, and 4P-2D Spike variants all protected female hamsters against heterologous challenge with the B.1.351 SARS-CoV-2 virus and elicited high titers of neutralizing antibodies. Conclusions: We suggest that destabilization of the postfusion conformation through the introduction of charged amino acids at sites that are exposed in the pre- and buried in the postfusion conformation offers a general strategy to enhance the yield and stability of the native, prefusion conformation of viral surface proteins. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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11 pages, 532 KiB

Open AccessArticle

Immune Imprinting, Non-Durable Hybrid Immunity, and Hybrid Immune Damping Following SARS-CoV-2 Primary Vaccination with BNT162b2 and Boosting with mRNA-1273

by Alejo Erice, Néstor Nuño, Lola Prieto and Cristina Caballero

Vaccines 2025, 13(3), 310; https://doi.org/10.3390/vaccines13030310 - 13 Mar 2025

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Abstract

Background/Objectives: Long-term studies on the immune response following multiple doses of SARS-CoV-2 mRNA vaccines remain limited. Methods: Secondary analyses of data from a cohort of non-immunocompromised subjects who received two doses of BNT162b2 (primary vaccination) and a booster with mRNA-1273 nine months later. [...] Read more.

Background/Objectives: Long-term studies on the immune response following multiple doses of SARS-CoV-2 mRNA vaccines remain limited. Methods: Secondary analyses of data from a cohort of non-immunocompromised subjects who received two doses of BNT162b2 (primary vaccination) and a booster with mRNA-1273 nine months later. Antibodies targeting the receptor-binding domain of the S1 subunit of the SARS-CoV-2 spike (anti-RBD) were measured at eight time points during follow-up; the SARS-CoV-2-specific T cell response was measured 16 and 25 months after primary vaccination using an interferon-γ release assay. Results: During the 9-month follow up period after primary vaccination and before the mRNA-1273 booster, anti-RBD were significantly higher at all time points in subjects with documented SARS-CoV-2 infection before the first study time point (previously infected subjects; n = 50) compared to naïve subjects (n = 208; p < 0.05). During a 16-month follow up period following the mRNA-1273 booster, anti-RBD were lower at all time points in previously infected subjects (n = 21) compared to naïve subjects (n = 109), although the differences were non-significant. Breakthrough SARS-CoV-2 infections increased over time in both groups, particularly after the mRNA-1273 booster. Most participants had a persistent SARS-CoV-2 specific T cell response regardless of prior infection. Conclusions: These findings suggest a modulating effect of previous SARS-CoV-2 infection on the humoral immune response to mRNA vaccination, a non-durable hybrid immunity following mRNA vaccination in previously infected subjects, and attenuation of the humoral immune response (immune damping) after repeated exposure to SARS-CoV-2 antigens through mRNA vaccination and/or infection. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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19 pages, 3637 KiB

Open AccessArticle

Jet Injection of Naked mRNA Encoding the RBD of the SARS-CoV-2 Spike Protein Induces a High Level of a Specific Immune Response in Mice

by Denis N. Kisakov, Larisa I. Karpenko, Lyubov A. Kisakova, Sergey V. Sharabrin, Mariya B. Borgoyakova, Ekaterina V. Starostina, Oleg S. Taranov, Elena K. Ivleva, Oleg V. Pyankov, Anna V. Zaykovskaya, Elena V. Dmitrienko, Vladimir A. Yakovlev, Elena V. Tigeeva, Irina Alekseevna Bauer, Svetlana I. Krasnikova, Nadezhda B. Rudometova, Andrey P. Rudometov, Artemiy A. Sergeev and Alexander A. Ilyichev

Vaccines 2025, 13(1), 65; https://doi.org/10.3390/vaccines13010065 - 13 Jan 2025

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Abstract

Background: Although mRNA vaccines encapsulated in lipid nanoparticles (LNPs) have demonstrated a safety profile with minimal serious adverse events in clinical trials, there is opportunity to further reduce mRNA reactogenicity. The development of naked mRNA vaccines could improve vaccine tolerability. Naked nucleic acid [...] Read more.

Background: Although mRNA vaccines encapsulated in lipid nanoparticles (LNPs) have demonstrated a safety profile with minimal serious adverse events in clinical trials, there is opportunity to further reduce mRNA reactogenicity. The development of naked mRNA vaccines could improve vaccine tolerability. Naked nucleic acid delivery using the jet injection method may be a solution. Methods: In the first part of the study, the optimal conditions providing low traumatization and high expression of the model mRNA-GFP molecule in the tissues of laboratory animals were determined. Then, we used the selected protocol to immunize BALB/c mice with mRNA-RBD encoding the SARS-CoV-2 receptor-binding domain (RBD). It was demonstrated that mice vaccinated with naked mRNA-RBD developed a high level of specific antibodies with virus-neutralizing activity. The vaccine also induced a strong RBD-specific T-cell response and reduced the viral load in the lungs of the animals after infection with the SARS-CoV-2 virus. The level of immune response in mice immunized with mRNA-RBD using a spring-loaded jet injector was comparable to that in animals immunized with mRNA-RBD encapsulated in LNPs. Results: In this study, the efficacy of an inexpensive, simple, and safe method of mRNA delivery using a spring-loaded jet injector was evaluated and validated. Conclusions: Our findings suggest that the jet injection method may be a possible alternative to LNPs for delivering mRNA vaccines against SARS-CoV-2 infection. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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19 pages, 3561 KiB

Open AccessArticle

Antibody Avidity Maturation Following Booster Vaccination with an Intranasal Adenovirus Salnavac Vaccine

by Ekaterina A. Astakhova, Konstantin O. Baranov, Nadezhda V. Shilova, Svetlana M. Polyakova, Evgeniy V. Zuev, Dmitry A. Poteryaev, Alexander V. Taranin and Alexander V. Filatov

Vaccines 2024, 12(12), 1362; https://doi.org/10.3390/vaccines12121362 - 2 Dec 2024

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Abstract

Background: The COVID-19 pandemic has led to the rapid development of new vaccines and methods of testing vaccine-induced immunity. Despite the extensive research that has been conducted on the level of specific antibodies, less attention has been paid to studying the avidity of [...] Read more.

Background: The COVID-19 pandemic has led to the rapid development of new vaccines and methods of testing vaccine-induced immunity. Despite the extensive research that has been conducted on the level of specific antibodies, less attention has been paid to studying the avidity of these antibodies. The avidity of serum antibodies is associated with a vaccine showing high effectiveness and reflects the process of affinity maturation. In the context of vaccines against SARS-CoV-2, only a limited number of studies have investigated the avidity of antibodies, often solely focusing on the wild-type virus following vaccination. This study provides new insights into the avidity of serum antibodies following adenovirus-based boosters. We focused on the effects of an intranasal Salnavac booster, which is compared, using a single analytical platform, to an intramuscular Sputnik V. Methods: The avidity of RBD-specific IgGs and IgAs was investigated through ELISA using urea and biolayer interferometry. Results: The results demonstrated the similar avidities of serum antibodies, which were induced by both vaccines for six months post-booster. However, an increase in antibody avidity was observed for the wild-type and Delta variants, but not for the BA.4/5 variant. Conclusions: Collectively, our data provide the insights into antibody avidity maturation after the adenovirus-based vaccines against SARS-CoV-2. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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10 pages, 2065 KiB

Open AccessArticle

Label-Free Quantitative Proteomics Analysis of COVID-19 Vaccines by Nano LC-HRMS

by Hengzhi Zhao, Wendong Li, Jingjing Liu, Xiao Li, Hong Ji, Mo Hu and Min Li

Vaccines 2024, 12(9), 1055; https://doi.org/10.3390/vaccines12091055 - 15 Sep 2024

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Abstract

A nanoliter liquid chromatography–high resolution mass spectrometry-based method was developed for quantitative proteomics analysis of COVID-19 vaccines. It can be used for simultaneous qualitative and quantitative analysis of target proteins and host cell proteins (HCPs) in vaccine samples. This approach can directly provide [...] Read more.

A nanoliter liquid chromatography–high resolution mass spectrometry-based method was developed for quantitative proteomics analysis of COVID-19 vaccines. It can be used for simultaneous qualitative and quantitative analysis of target proteins and host cell proteins (HCPs) in vaccine samples. This approach can directly provide protein information at the molecular level. Based on this, the proteomes of 15 batches of COVID-19 inactivated vaccine samples from two companies and 12 batches of COVID-19 recombinant protein vaccine samples from one company were successfully analyzed, which provided a significant amount of valuable information. Samples produced in different batches or by different companies can be systematically contrasted in this way, offering powerful supplements for existing quality standards. This strategy paves the way for profiling proteomics in complex samples and provides a novel perspective on the quality evaluation of bio-macromolecular drugs. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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26 pages, 5429 KiB

Open AccessArticle

Beta Spike-Presenting SARS-CoV-2 Virus-like Particle Vaccine Confers Broad Protection against Other VOCs in Mice

by Irfan Ullah, Kelly Symmes, Kadiatou Keita, Li Zhu, Michael W. Grunst, Wenwei Li, Walther Mothes, Priti Kumar and Pradeep D. Uchil

Vaccines 2024, 12(9), 1007; https://doi.org/10.3390/vaccines12091007 - 2 Sep 2024

Cited by 2 | Viewed by 1622

Abstract

Virus-like particles (VLPs) are non-infectious and serve as promising vaccine platforms because they mimic the membrane-embedded conformations of fusion glycoproteins on native viruses. Here, we employed SARS-CoV-2 VLPs (SMEN) presenting ancestral, Beta, or Omicron spikes to identify the variant spike that elicits potent [...] Read more.

Virus-like particles (VLPs) are non-infectious and serve as promising vaccine platforms because they mimic the membrane-embedded conformations of fusion glycoproteins on native viruses. Here, we employed SARS-CoV-2 VLPs (SMEN) presenting ancestral, Beta, or Omicron spikes to identify the variant spike that elicits potent and cross-protective immune responses in the highly sensitive K18-hACE2 challenge mouse model. A combined intranasal and intramuscular SMEN vaccine regimen generated the most effective immune responses to significantly reduce disease burden. Protection was primarily mediated by antibodies, with minor but distinct contributions from T cells in reducing virus spread and inflammation. Immunization with SMEN carrying ancestral spike resulted in 100, 75, or 0% protection against ancestral, Delta, or Beta variant-induced mortality, respectively. However, SMEN with an Omicron spike provided only limited protection against ancestral (50%), Delta (0%), and Beta (25%) challenges. By contrast, SMEN with Beta spikes offered 100% protection against the variants used in this study. Thus, the Beta variant not only overcame the immunity produced by other variants, but the Beta spike also elicited diverse and effective humoral immune responses. Our findings suggest that leveraging the Beta variant spike protein can enhance SARS-CoV-2 immunity, potentially leading to a more comprehensive vaccine against emerging variants. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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17 pages, 3473 KiB

Open AccessArticle

Omicron XBB.1.16-Adapted Vaccine for COVID-19: Interim Immunogenicity and Safety Clinical Trial Results

by María Jesús López Fernández, Silvia Narejos, Antoni Castro, José María Echave-Sustaeta, María José Forner, Eunate Arana-Arri, José Molto, Laia Bernad, Raúl Pérez-Caballero, Julia G. Prado, Dàlia Raïch-Regué, Rytis Boreika, Nuria Izquierdo-Useros, Benjamin Trinité, Julià Blanco, Joan Puig-Barberà and Silvina Natalini Martínez

Vaccines 2024, 12(8), 840; https://doi.org/10.3390/vaccines12080840 - 25 Jul 2024

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Abstract

(1) Background: The global coronavirus disease 2019 vaccination adapts to protect populations from emerging variants. This communication presents interim findings from the new Omicron XBB.1.16-adapted PHH-1V81 protein-based vaccine compared to an XBB.1.5-adapted mRNA vaccine against various acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains. [...] Read more.

(1) Background: The global coronavirus disease 2019 vaccination adapts to protect populations from emerging variants. This communication presents interim findings from the new Omicron XBB.1.16-adapted PHH-1V81 protein-based vaccine compared to an XBB.1.5-adapted mRNA vaccine against various acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains. (2) Methods: In a Phase IIb/III pivotal trial, adults previously vaccinated with a primary scheme and at least one booster dose of an EU-approved mRNA vaccine randomly received either the PHH-1V81 or BNT162b2 XBB.1.5 vaccine booster as a single dose. The primary efficacy endpoint assessed neutralization titers against the Omicron XBB.1.16 variant at day 14. Secondary endpoints evaluated neutralization titers and cellular immunity against different variants. Safety endpoints comprised solicited reactions up to day 7 post-vaccination and serious adverse events until the cut-off date of the interim analysis. Changes in humoral responses were assessed by pseudovirion-based or virus neutralization assays. (3) Results: At the cut-off date, immunogenicity assessments included 599 participants. Both boosters elicited neutralizing antibodies against XBB.1.16, XBB.1.5, and JN.1, with PHH-1V81 inducing a higher response for all variants. The PHH-1V8 booster triggers a superior neutralizing antibody response against XBB variants compared to the mRNA vaccine. A subgroup analysis consistently revealed higher neutralizing antibody responses with PHH-1V81 across age groups, SARS-CoV-2 infection history, and the number of prior vaccination shots. A safety analysis (n = 607) at the day 14 visit revealed favorable safety profiles without any serious vaccine-related adverse events. (4) Conclusions: PHH-1V81 demonstrates superiority on humoral immunogenicity compared to the mRNA vaccine against XBB variants and non-inferiority against JN.1 with a favorable safety profile and lower reactogenicity, confirming its potential as a vaccine candidate. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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14 pages, 2537 KiB

Open AccessArticle

Equal Maintenance of Anti-SARS-CoV-2 Antibody Levels Induced by Heterologous and Homologous Regimens of the BNT162b2, ChAdOx1, CoronaVac and Ad26.COV2.S Vaccines: A Longitudinal Study Up to the 4th Dose of Booster

by Tatiana A. do Nascimento, Patricia Y. Nogami, Camille F. de Oliveira, Walter F. F. Neto, Carla P. da Silva, Ana Claudia S. Ribeiro, Alana W. de Sousa, Maria N. O. Freitas, Jannifer O. Chiang, Franko A. Silva, Liliane L. das Chagas, Valéria L. Carvalho, Raimunda S. S. Azevedo, Pedro F. C. Vasconcelos, Igor B. Costa, Iran B. Costa, Luana S. Barbagelata, Wanderley D. das Chagas Junior, Edvaldo T. da Penha Junior, Luana S. Soares, Giselle M. R. Viana, Alberto A. Amarilla, Naphak Modhiran, Daniel Watterson, Lívia M. N. Casseb, Lívia C. Martins and Daniele F. Henriques Show full author list Hide full author list

Vaccines 2024, 12(7), 792; https://doi.org/10.3390/vaccines12070792 - 18 Jul 2024

Cited by 3 | Viewed by 1356

Abstract

Several technological approaches have been used to develop vaccines against COVID-19, including those based on inactivated viruses, viral vectors, and mRNA. This study aimed to monitor the maintenance of anti-SARS-CoV-2 antibodies in individuals from Brazil according to the primary vaccination regimen, as follows: [...] Read more.

Several technological approaches have been used to develop vaccines against COVID-19, including those based on inactivated viruses, viral vectors, and mRNA. This study aimed to monitor the maintenance of anti-SARS-CoV-2 antibodies in individuals from Brazil according to the primary vaccination regimen, as follows: BNT162b2 (group 1; 22) and ChAdOx1 (group 2; 18). Everyone received BNT162b2 in the first booster while in the second booster CoronaVac, Ad26.COV2.S, or BNT162b2. Blood samples were collected from 2021 to 2023 to analyze specific RBD (ELISA) and neutralizing antibodies (PRNT50). We observed a progressive increase in anti-RBD and neutralizing antibodies in each subsequent dose, remaining at high titers until the end of follow-up. Group 1 had higher anti-RBD antibody titers than group 2 after beginning the primary regimen, with significant differences after the 2nd and 3rd doses. Group 2 showed a more expressive increase after the first booster with BNT162B2 (heterologous booster). Group 2 also presented high levels of neutralizing antibodies against the Gamma and Delta variants until five months after the second booster. In conclusion, the circulating levels of anti-RBD and neutralizing antibodies against the two variants of SARS-CoV-2 were durable even five months after the 4th dose, suggesting that periodic booster vaccinations (homologous or heterologous) induced long-lasting immunity. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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16 pages, 1509 KiB

Open AccessArticle

Immunogenicity and Protective Efficacy of a Single Intranasal Dose Vectored Vaccine Based on Sendai Virus (Moscow Strain) against SARS-CoV-2 Variant of Concern

by Galina V. Kochneva, Gleb A. Kudrov, Sergei S. Zainutdinov, Irina S. Shulgina, Andrei V. Shipovalov, Anna V. Zaykovskaya, Mariya B. Borgoyakova, Ekaterina V. Starostina, Sergei A. Bodnev, Galina F. Sivolobova, Antonina A. Grazhdantseva, Daria I. Ivkina, Alexey M. Zadorozhny, Larisa I. Karpenko and Oleg V. P’yankov

Vaccines 2024, 12(7), 783; https://doi.org/10.3390/vaccines12070783 - 16 Jul 2024

Cited by 1 | Viewed by 1695

Abstract

The mouse paramyxovirus Sendai, which is capable of limited replication in human bronchial epithelial cells without causing disease, is well suited for the development of vector-based intranasal vaccines against respiratory infections, including SARS-CoV-2. Using the Moscow strain of the Sendai virus, we developed [...] Read more.

The mouse paramyxovirus Sendai, which is capable of limited replication in human bronchial epithelial cells without causing disease, is well suited for the development of vector-based intranasal vaccines against respiratory infections, including SARS-CoV-2. Using the Moscow strain of the Sendai virus, we developed a vaccine construct, Sen-Sdelta(M), which expresses the full-length spike (S) protein of the SARS-CoV-2 delta variant. A single intranasal delivery of Sen-Sdelta(M) to Syrian hamsters and BALB/c mice induced high titers of virus-neutralizing antibodies specific to the SARS-CoV-2 delta variant. A significant T-cell response, as determined by IFN-γ ELISpot and ICS methods, was also demonstrated in the mouse model. Mice and hamsters vaccinated with Sen-Sdelta(M) were well protected against SARS-CoV-2 challenge. The viral load in the lungs and nasal turbinates, measured by RT-qPCR and TCID₅₀ assay, decreased dramatically in vaccinated groups. The most prominent effect was revealed in a highly sensitive hamster model, where no tissue samples contained detectable levels of infectious SARS-CoV-2. These results indicate that Sen-Sdelta(M) is a promising candidate as a single-dose intranasal vaccine against SARS-CoV-2, including variants of concern. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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13 pages, 3188 KiB

Open AccessArticle

Longitudinal Assessment of BNT162b2- and mRNA-1273-Induced Anti-SARS-CoV-2 Spike IgG Levels and Avidity Following Three Doses of Vaccination

by Jimmie L. Bullock, Jr., Thomas E. Hickey, Troy J. Kemp, Jordan Metz, Sarah Loftus, Katarzyna Haynesworth, Nicholas Castro, Brian T. Luke, Douglas R. Lowy and Ligia A. Pinto

Vaccines 2024, 12(5), 516; https://doi.org/10.3390/vaccines12050516 - 9 May 2024

Cited by 5 | Viewed by 2094

Abstract

SARS-CoV-2 vaccination-induced protection against infection is likely to be affected by functional antibody features. To understand the kinetics of antibody responses in healthy individuals after primary series and third vaccine doses, sera from the recipients of the two licensed SARS-CoV-2 mRNA vaccines were [...] Read more.

SARS-CoV-2 vaccination-induced protection against infection is likely to be affected by functional antibody features. To understand the kinetics of antibody responses in healthy individuals after primary series and third vaccine doses, sera from the recipients of the two licensed SARS-CoV-2 mRNA vaccines were assessed for circulating anti-SARS-CoV-2 spike IgG levels and avidity for up to 6 months post-primary series and 9 months after the third dose. Following primary series vaccination, anti-SARS-CoV-2 spike IgG levels declined from months 1 to 6, while avidity increased through month 6, irrespective of the vaccine received. The third dose of either vaccine increased anti-SARS-CoV-2 spike IgG levels and avidity and appeared to enhance antibody level persistence—generating a slower rate of decline in the 3 months following the third dose compared to the decline seen after the primary series alone. The third dose of both vaccines induced significant avidity increases 1 month after vaccination compared to the avidity response 6 months post-primary series vaccination (p ≤ 0.001). A significant difference in avidity responses between the two vaccines was observed 6 months post-third dose, where the BNT162b2 recipients had higher antibody avidity levels compared to the mRNA-1273 recipients (p = 0.020). Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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24 pages, 3241 KiB

Open AccessArticle

Induction of Superior Systemic and Mucosal Protective Immunity to SARS-CoV-2 by Nasal Administration of a VSV–ΔG–Spike Vaccine

by Yfat Yahalom-Ronen, Sharon Melamed, Boaz Politi, Noam Erez, Hadas Tamir, Liat Bar-On, Julia Ryvkin, Dena Leshkowitz, Ofir Israeli, Shay Weiss, Amir Ben-Shmuel, Moria Barlev-Gross, Lilach Cherry Mimran, Hagit Achdout, Nir Paran and Tomer Israely

Vaccines 2024, 12(5), 491; https://doi.org/10.3390/vaccines12050491 - 1 May 2024

Cited by 5 | Viewed by 2538

Abstract

The emergence of rapidly spreading variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) poses a major challenge to vaccines’ protective efficacy. Intramuscular (IM) vaccine administration induces short-lived immunity but does not prevent infection and transmission. New vaccination strategies are needed to extend [...] Read more.

The emergence of rapidly spreading variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) poses a major challenge to vaccines’ protective efficacy. Intramuscular (IM) vaccine administration induces short-lived immunity but does not prevent infection and transmission. New vaccination strategies are needed to extend the longevity of vaccine protection, induce mucosal and systemic immunity and prevent viral transmission. The intranasal (IN) administration of the VSV–ΔG–spike vaccine candidate directly to mucosal surfaces yielded superior mucosal and systemic immunity at lower vaccine doses. Compared to IM vaccination in the K18–hACE2 model, IN vaccination preferentially induced mucosal IgA and T-cells, reduced the viral load at the site of infection, and ameliorated disease-associated brain gene expression. IN vaccination was protective even one year after administration. As most of the world population has been vaccinated by IM injection, we demonstrate the potential of a heterologous IM + IN vaccination regimen to induce mucosal immunity while maintaining systemic immunity. Furthermore, the IM + IN regimen prevented virus transmission in a golden Syrian hamster co-caging model. Taken together, we show that IN vaccination with VSV–ΔG–spike, either as a homologous IN + IN regimen or as a boost following IM vaccination, has a favorable potential over IM vaccination in inducing efficient mucosal immunity, long-term protection and preventing virus transmission. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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19 pages, 1901 KiB

Open AccessArticle

Major Role of S-Glycoprotein in Providing Immunogenicity and Protective Immunity in mRNA Lipid Nanoparticle Vaccines Based on SARS-CoV-2 Structural Proteins

by Evgeniia N. Bykonia, Denis A. Kleymenov, Vladimir A. Gushchin, Andrei E. Siniavin, Elena P. Mazunina, Sofia R. Kozlova, Anastasia N. Zolotar, Evgeny V. Usachev, Nadezhda A. Kuznetsova, Elena V. Shidlovskaya, Andrei A. Pochtovyi, Daria D. Kustova, Igor A. Ivanov, Sergey E. Dmitriev, Roman A. Ivanov, Denis Y. Logunov and Alexander L. Gintsburg

Vaccines 2024, 12(4), 379; https://doi.org/10.3390/vaccines12040379 - 2 Apr 2024

Cited by 2 | Viewed by 2682

Abstract

SARS-CoV-2 variants have evolved over time in recent years, demonstrating immune evasion of vaccine-induced neutralizing antibodies directed against the original S protein. Updated S-targeted vaccines provide a high level of protection against circulating variants of SARS-CoV-2, but this protection declines over time due [...] Read more.

SARS-CoV-2 variants have evolved over time in recent years, demonstrating immune evasion of vaccine-induced neutralizing antibodies directed against the original S protein. Updated S-targeted vaccines provide a high level of protection against circulating variants of SARS-CoV-2, but this protection declines over time due to ongoing virus evolution. To achieve a broader protection, novel vaccine candidates involving additional antigens with low mutation rates are currently needed. Based on our recently studied mRNA lipid nanoparticle (mRNA-LNP) platform, we have generated mRNA-LNP encoding SARS-CoV-2 structural proteins M, N, S from different virus variants and studied their immunogenicity separately or in combination in vivo. As a result, all mRNA-LNP vaccine compositions encoding the S and N proteins induced excellent titers of RBD- and N-specific binding antibodies. The T cell responses were mainly specific CD4⁺ T cell lymphocytes producing IL-2 and TNF-alpha. mRNA-LNP encoding the M protein did not show a high immunogenicity. High neutralizing activity was detected in the sera of mice vaccinated with mRNA-LNP encoding S protein (alone or in combinations) against closely related strains, but was undetectable or significantly lower against an evolutionarily distant variant. Our data showed that the addition of mRNAs encoding S and M antigens to mRNA-N in the vaccine composition enhanced the immunogenicity of mRNA-N and induced a more robust immune response to the N protein. Based on our results, we suggested that the S protein plays a key role in enhancing the immune response to the N protein when they are both encoded in the mRNA-LNP vaccine. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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18 pages, 2426 KiB

Open AccessArticle

SARS-CoV-2 Neutralization Capacity in Hemodialysis Patients with and without a Fifth Vaccination with the Updated Comirnaty Original/Omicron BA.4-5 Vaccine

by Bo-Hung Liao, Louise Platen, Myriam Grommes, Cho-Chin Cheng, Christopher Holzmann-Littig, Catharina Christa, Bernhard Haller, Verena Kappler, Romina Bester, Maia Lucia Werz, Eva Platen, Peter Eggerer, Laëtitia Tréguer, Claudius Küchle, Christoph Schmaderer, Uwe Heemann, Lutz Renders, Ulrike Protzer and Matthias Christoph Braunisch

Vaccines 2024, 12(3), 308; https://doi.org/10.3390/vaccines12030308 - 15 Mar 2024

Cited by 2 | Viewed by 2049

Abstract

Background: Hemodialysis patients have reduced serologic immunity after SARS-CoV-2 vaccination compared to the general population and an increased risk of morbidity and mortality when exposed to SARS-CoV-2. Methods: Sixty-six hemodialysis patients immunized four times with the original SARS-CoV-2 vaccines (BNT162b2, mRNA-1273) either received [...] Read more.

Background: Hemodialysis patients have reduced serologic immunity after SARS-CoV-2 vaccination compared to the general population and an increased risk of morbidity and mortality when exposed to SARS-CoV-2. Methods: Sixty-six hemodialysis patients immunized four times with the original SARS-CoV-2 vaccines (BNT162b2, mRNA-1273) either received a booster with the adapted Comirnaty Original/Omicron BA.4-5 vaccine 8.3 months after the fourth vaccination and/or experienced a breakthrough infection. Two months before and four weeks after the fifth vaccination, the live-virus neutralization capacities of Omicron variants BA.5, BQ.1.1, and XBB.1.5 were determined, as well as neutralizing and quantitative anti-SARS-CoV-2 spike-specific IgG antibodies. Results: Four weeks after the fifth vaccination with the adapted vaccine, significantly increased neutralizing antibodies and the neutralization of Omicron variants BA.5, BQ.1.1, and XBB.1.5 were observed. The increase was significantly higher than after the fourth vaccination for variants BQ.1.1 and BA.5. Of all analyzed variants, BA.5 was neutralized best after the fifth vaccination. We did not see a difference in humoral immunity between the group with an infection and the group with a vaccination as a fifth spike exposure. Fivefold-vaccinated patients with a breakthrough infection showed a significantly higher neutralization capacity of XBB.1.5. Conclusion: A fifth SARS-CoV-2 vaccination with the adapted vaccine improves both wild-type specific antibody titers and the neutralizing capacity of the current Omicron variants BA.5, BQ.1.1, and XBB.1.5 in hemodialysis patients. Additional booster vaccinations with adapted vaccines will likely improve immunity towards current and original SARS-CoV-2 variants and are, therefore, recommended in hemodialysis patients. Further longitudinal studies must show the extent to which this booster vaccination avoids a breakthrough infection. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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12 pages, 835 KiB

Open AccessArticle

In Vitro Efficacy of Antivirals and Monoclonal Antibodies against SARS-CoV-2 Omicron Lineages XBB.1.9.1, XBB.1.9.3, XBB.1.5, XBB.1.16, XBB.2.4, BQ.1.1.45, CH.1.1, and CL.1

by Andrei A. Pochtovyi, Daria D. Kustova, Andrei E. Siniavin, Inna V. Dolzhikova, Elena V. Shidlovskaya, Olga G. Shpakova, Lyudmila A. Vasilchenko, Arina A. Glavatskaya, Nadezhda A. Kuznetsova, Anna A. Iliukhina, Artem Y. Shelkov, Olesia M. Grinkevich, Andrei G. Komarov, Denis Y. Logunov, Vladimir A. Gushchin and Alexander L. Gintsburg

Vaccines 2023, 11(10), 1533; https://doi.org/10.3390/vaccines11101533 - 28 Sep 2023

Cited by 18 | Viewed by 2714

Abstract

The spread of COVID-19 continues, expressed by periodic wave-like increases in morbidity and mortality. The reason for the periodic increases in morbidity is the emergence and spread of novel genetic variants of SARS-CoV-2. A decrease in the efficacy of monoclonal antibodies (mAbs) has [...] Read more.

The spread of COVID-19 continues, expressed by periodic wave-like increases in morbidity and mortality. The reason for the periodic increases in morbidity is the emergence and spread of novel genetic variants of SARS-CoV-2. A decrease in the efficacy of monoclonal antibodies (mAbs) has been reported, especially against Omicron subvariants. There have been reports of a decrease in the efficacy of specific antiviral drugs as a result of mutations in the genes of non-structural proteins. This indicates the urgent need for practical healthcare to constantly monitor pathogen variability and its effect on the efficacy of preventive and therapeutic drugs. As part of this study, we report the results of the continuous monitoring of COVID-19 in Moscow using genetic and virological methods. As a result of this monitoring, we determined the dominant genetic variants and identified the variants that are most widespread, not only in Moscow, but also in other countries. A collection of viruses from more than 500 SARS-CoV-2 isolates has been obtained and characterized. The genetic lines XBB.1.9.1, XBB.1.9.3, XBB.1.5, XBB.1.16, XBB.2.4, BQ.1.1.45, CH.1.1, and CL.1, representing the greatest concern, were identified among the dominant variants. We studied the in vitro efficacy of mAbs Tixagevimab + Cilgavimab (Evusheld), Sotrovimab, Regdanvimab, Casirivimab + Imdevimab (Ronapreve), and Bebtelovimab, as well as the specific antiviral drugs Remdesivir, Molnupiravir, and Nirmatrelvir, against these genetic lines. At the current stage of the COVID-19 pandemic, the use of mAbs developed against early SARS-CoV-2 variants has little prospect. Specific antiviral drugs retain their activity, but further monitoring is needed to assess the risk of their efficacy being reduced and adjust recommendations for their use. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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Review

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50 pages, 3587 KiB

Open AccessReview

Beyond the Pandemic Era: Recent Advances and Efficacy of SARS-CoV-2 Vaccines Against Emerging Variants of Concern

by Ankita Saha, Sounak Ghosh Roy, Richa Dwivedi, Prajna Tripathi, Kamal Kumar, Shashank Manohar Nambiar and Rajiv Pathak

Vaccines 2025, 13(4), 424; https://doi.org/10.3390/vaccines13040424 - 17 Apr 2025

Viewed by 1818

Abstract

Vaccination has been instrumental in curbing the transmission of SARS-CoV-2 and mitigating the severity of clinical manifestations associated with COVID-19. Numerous COVID-19 vaccines have been developed to this effect, including BioNTech-Pfizer and Moderna’s mRNA vaccines, as well as adenovirus vector-based vaccines such as [...] Read more.

Vaccination has been instrumental in curbing the transmission of SARS-CoV-2 and mitigating the severity of clinical manifestations associated with COVID-19. Numerous COVID-19 vaccines have been developed to this effect, including BioNTech-Pfizer and Moderna’s mRNA vaccines, as well as adenovirus vector-based vaccines such as Oxford–AstraZeneca. However, the emergence of new variants and subvariants of SARS-CoV-2, characterized by enhanced transmissibility and immune evasion, poses significant challenges to the efficacy of current vaccination strategies. In this review, we aim to comprehensively outline the landscape of emerging SARS-CoV-2 variants of concern (VOCs) and sub-lineages that have recently surfaced in the post-pandemic years. We assess the effectiveness of existing vaccines, including their booster doses, against these emerging variants and subvariants, such as BA.2-derived sub-lineages, XBB sub-lineages, and BA.2.86 (Pirola). Furthermore, we discuss the latest advancements in vaccine technology, including multivalent and pan-coronavirus approaches, along with the development of several next-generation coronavirus vaccines, such as exosome-based, virus-like particle (VLP), mucosal, and nanomaterial-based vaccines. Finally, we highlight the key challenges and critical areas for future research to address the evolving threat of SARS-CoV-2 subvariants and to develop strategies for combating the emergence of new viral threats, thereby improving preparedness for future pandemics. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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17 pages, 616 KiB

Open AccessReview

Hybrid Immunity against SARS-CoV-2 Variants: A Narrative Review of the Literature

by Panagiota Tsagkli, Maria Geropeppa, Ioanna Papadatou and Vana Spoulou

Vaccines 2024, 12(9), 1051; https://doi.org/10.3390/vaccines12091051 - 14 Sep 2024

Cited by 4 | Viewed by 2899

Abstract

The emergence of SARS-CoV-2 led to a global health crisis and the burden of the disease continues to persist. The rapid development and emergency authorization of various vaccines, including mRNA-based vaccines, played a pivotal role in mitigating severe illness and mortality. However, rapid [...] Read more.

The emergence of SARS-CoV-2 led to a global health crisis and the burden of the disease continues to persist. The rapid development and emergency authorization of various vaccines, including mRNA-based vaccines, played a pivotal role in mitigating severe illness and mortality. However, rapid viral mutations, leading to several variants of concern, challenged vaccine effectiveness, particularly concerning immune evasion. Research on immunity, both from natural infection and vaccination, revealed that while neutralizing antibodies provide protection against infection, their effect is short-lived. The primary defense against severe COVID-19 is derived from the cellular immune response. Hybrid immunity, developed from a combination of natural infection and vaccination, offers enhanced protection, with convalescent vaccinated individuals showing significantly higher levels of neutralizing antibodies. As SARS-CoV-2 continues to evolve, understanding the durability and breadth of hybrid immunity becomes crucial. This narrative review examines the latest data on humoral and cellular immunity from both natural infection and vaccination, discussing how hybrid immunity could inform and optimize future vaccination strategies in the ongoing battle against COVID-19 and in fear of a new pandemic. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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18 pages, 2061 KiB

Open AccessReview

Functionally Designed Nanovaccines against SARS-CoV-2 and Its Variants

by Yue Xi, Rongrong Ma, Shuo Li, Gang Liu and Chao Liu

Vaccines 2024, 12(7), 764; https://doi.org/10.3390/vaccines12070764 - 12 Jul 2024

Cited by 2 | Viewed by 2678

Abstract

COVID-19, generated by SARS-CoV-2, has significantly affected healthcare systems worldwide. The epidemic has highlighted the urgent need for vaccine development. Besides the conventional vaccination models, which include live-attenuated, recombinant protein, and inactivated vaccines, nanovaccines present a distinct opportunity to progress vaccine research and [...] Read more.

COVID-19, generated by SARS-CoV-2, has significantly affected healthcare systems worldwide. The epidemic has highlighted the urgent need for vaccine development. Besides the conventional vaccination models, which include live-attenuated, recombinant protein, and inactivated vaccines, nanovaccines present a distinct opportunity to progress vaccine research and offer convenient alternatives. This review highlights the many widely used nanoparticle vaccine vectors, outlines their benefits and drawbacks, and examines recent developments in nanoparticle vaccines to prevent SARS-CoV-2. It also offers a thorough overview of the many advantages of nanoparticle vaccines, including an enhanced host immune response, multivalent antigen delivery, and efficient drug delivery. The main objective is to provide a reference for the development of innovative antiviral vaccines. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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Other

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14 pages, 867 KiB

Open AccessBrief Report

Serological Correlate of Protection Established by Neutralizing Antibodies Differs Among Dialysis Patients with SARS-CoV-2 Variants of Concern

by Guy Rostoker, Stéphanie Rouanet, Myriam Merzoug, Hiba Chakaroun, Mireille Griuncelli, Christelle Loridon, Ghada Boulahia and Luc Gagnon

Vaccines 2025, 13(5), 518; https://doi.org/10.3390/vaccines13050518 - 13 May 2025

Viewed by 453

Abstract

Background: The 2019 coronavirus disease (COVID-19) pandemic had a severe impact on frail, end-stage kidney disease (ESKD) patients, either on dialysis or transplanted, with a high mortality rate in the early waves. Vaccination against SARS-CoV-2 with mRNA vaccines has led to reduced hospitalization [...] Read more.

Background: The 2019 coronavirus disease (COVID-19) pandemic had a severe impact on frail, end-stage kidney disease (ESKD) patients, either on dialysis or transplanted, with a high mortality rate in the early waves. Vaccination against SARS-CoV-2 with mRNA vaccines has led to reduced hospitalization and mortality rates in the general population and ESKD patients. Neutralizing antibodies (NAbs) are a valuable correlate of protection after vaccination, and IgG anti-spike antibodies are considered a surrogate marker of protection. Methods: This study investigated the correlates of protection brought by NAb and anti-spike IgG antibodies against SARS-CoV-2 wild-type Wuhan strain and variants of concern in a cohort of 128 French patients on dialysis after vaccination with the BNT162b2 mRNA vaccine. The correlate was assessed using Receiver Operating Characteristic curves. Results: The level of protection for IgG anti-spike antibodies was set at 917 BAU/mL for the original Wuhan strain and 980 BAU/mL and 1450 BAU/mL, respectively, for the Delta and Omicron BA.1 variants. Conclusions: The level of protection can be regularly monitored by measuring IgG anti-spike antibody concentrations to allow tailored boosters of SARS-CoV-2 vaccination in this frail and immunocompromised ESKD population. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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14 pages, 2044 KiB

Open AccessBrief Report

Entry Efficiency, Protease Dependence, and Antibody-Mediated Neutralization of SARS-CoV-2 Sublineages KP.3.1.1 and XEC

by Prerna Arora, Amy Kempf, Inga Nehlmeier, Sebastian R. Schulz, Hans-Martin Jäck, Markus Hoffmann and Stefan Pöhlmann

Vaccines 2025, 13(4), 385; https://doi.org/10.3390/vaccines13040385 - 3 Apr 2025

Viewed by 580

Abstract

Background: The SARS-CoV-2 variants KP.3.1.1 and XEC currently dominate the COVID-19 epidemic. However, their cell tropism, proteolytic processing, and susceptibility to neutralization by monoclonal antibodies remain incompletely characterized. Methods: We employed pseudotyped viruses to assess the entry efficiency of KP.3.1.1 and XEC in [...] Read more.

Background: The SARS-CoV-2 variants KP.3.1.1 and XEC currently dominate the COVID-19 epidemic. However, their cell tropism, proteolytic processing, and susceptibility to neutralization by monoclonal antibodies remain incompletely characterized. Methods: We employed pseudotyped viruses to assess the entry efficiency of KP.3.1.1 and XEC in various cell lines, their dependence on TMPRSS2 for lung cell entry, and their ability to use ACE2 for infection. Additionally, we evaluated their susceptibility to neutralization by monoclonal antibodies BD55-4637 and BD55-5514. Results: KP.3.1.1 and XEC entered cell lines with similar efficiency as the parental JN.1 lineage and utilized TMPRSS2 for Calu-3 lung cell entry. Unlike JN.1, KP.3.1.1 and XEC failed to efficiently use murine ACE2 for cell entry. Both variants were effectively neutralized by the monoclonal antibodies BD55-4637 and BD55-5514, suggesting therapeutic potential. Conclusions: Our findings demonstrate that JN.1, KP.3.1.1, and XEC, like their predecessor BA.2.86, rely on TMPRSS2 for lung cell entry and remain sensitive to certain neutralizing monoclonal antibodies. However, these variants differ in their ability to utilize ACE2 species orthologs for cell entry. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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18 pages, 1779 KiB

Open AccessBrief Report

Comparative Analysis of Host Cell Entry Efficiency and Neutralization Sensitivity of Emerging SARS-CoV-2 Lineages KP.2, KP.2.3, KP.3, and LB.1

by Nianzhen Chen, Katharina Emma Decker, Sebastian R. Schulz, Amy Kempf, Inga Nehlmeier, Anna-Sophie Moldenhauer, Alexandra Dopfer-Jablonka, Georg M. N. Behrens, Metodi V. Stankov, Luis Manthey, Hans-Martin Jäck, Markus Hoffmann, Stefan Pöhlmann and Prerna Arora

Vaccines 2024, 12(11), 1236; https://doi.org/10.3390/vaccines12111236 - 30 Oct 2024

Cited by 1 | Viewed by 2143

Abstract

New SARS-CoV-2 lineages continue to evolve and may exhibit new characteristics regarding host cell entry efficiency and potential for antibody evasion. Here, employing pseudotyped particles, we compared the host cell entry efficiency, ACE2 receptor usage, and sensitivity to antibody-mediated neutralization of four emerging [...] Read more.

New SARS-CoV-2 lineages continue to evolve and may exhibit new characteristics regarding host cell entry efficiency and potential for antibody evasion. Here, employing pseudotyped particles, we compared the host cell entry efficiency, ACE2 receptor usage, and sensitivity to antibody-mediated neutralization of four emerging SARS-CoV-2 lineages, KP.2, KP.2.3, KP.3, and LB.1. The XBB.1.5 and JN.1 lineages served as controls. Our findings reveal that KP.2, KP.2.3, KP.3, and LB.1 lineages enter host cells efficiently and in an ACE2-dependent manner, and that KP.3 is more adept at entering Calu-3 lung cells than JN.1. However, the variants differed in their capacity to employ ACE2 orthologues from animal species for entry, suggesting differences in ACE2 interactions. Moreover, we demonstrate that only two out of seven therapeutic monoclonal antibody (mAbs) in preclinical development retain robust neutralizing activity against the emerging JN.1 sublineages tested, while three mAbs displayed strongly reduced neutralizing activity and two mAbs lacked neutralizing activity against any of the lineages tested. Furthermore, our results show that KP.2, KP.2.3, KP.3, and LB.1 lineages evade neutralization by antibodies induced by infection or vaccination with greater efficiency than JN.1, particularly in individuals without hybrid immunity. This study indicates that KP.2, KP.2.3, KP.3, and LB.1 differ in ACE2 interactions and the efficiency of lung cell entry and suggest that evasion of neutralizing antibodies drove the emergence of these variants. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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19 pages, 2290 KiB

Open AccessSystematic Review

Safety, Immunogenicity, and Effectiveness of Chinese-Made COVID-19 Vaccines in the Real World: An Interim Report of a Living Systematic Review

by Yangyang Qi, Hui Zheng, Jinxia Wang, Yani Chen, Xu Guo, Zheng Li, Wei Zhang, Jiajia Zhou, Songmei Wang, Boyi Lin, Lin Zhang, Tingting Yan, John Clemens, Jielai Xia, Zhijie An, Zundong Yin, Xuanyi Wang and Zijian Feng

Vaccines 2024, 12(7), 781; https://doi.org/10.3390/vaccines12070781 - 16 Jul 2024

Cited by 2 | Viewed by 2357

Abstract

Background: Several COVID-19 vaccines were developed and approved in China. Of these, the BIBB-CorV and CoronaVac inactivated whole-virion vaccines were widely distributed in China and developing countries. However, the performance of the two vaccines in the real world has not been summarized. Methods: [...] Read more.

Background: Several COVID-19 vaccines were developed and approved in China. Of these, the BIBB-CorV and CoronaVac inactivated whole-virion vaccines were widely distributed in China and developing countries. However, the performance of the two vaccines in the real world has not been summarized. Methods: A living systematic review based on findings from ongoing post-licensure studies was conducted, applying standardized algorithms. Articles published between 1 May 2020 and 31 May 2022 in English and Chinese were searched for in Medline, Embase, WanFang Data, medRxiv, bioRxiv, arXiv, SSRN, and Research Square, using SARS-CoV-2, COVID-19, and vaccine as the MeSH terms. Studies with estimates of safety, immunogenicity, and effectiveness from receiving the BIBB-CorV or CoronaVac vaccine that met the predefined screening criteria underwent a full-text review. The Joanna Briggs Institute’s Critical Appraisal Checklist and the Cochrane risk of bias were used for assessment of the quality. A random-effects meta-regression model was applied to identify the potential impact factors on the vaccines’ effectiveness. Results: In total, 32578 articles were identified, of these, 770 studies underwent a full-text review. Eventually, 213 studies were included. The pooled occurrence of solicited and unsolicited adverse events after any dose of either vaccine varied between 10% and 40%. The top five commonly reported rare adverse events were immunization stress-related responses (211 cases, 50.0%), cutaneous responses (43 cases, 10.2%), acute neurological syndrome (39 cases, 9.2%), anaphylaxis (17 cases, 4.0%), and acute stroke (16 cases, 3.8%). The majority (83.3%) recovered or were relieved within several days. The peak neutralization titers against the ancestral strain was found within 1 month after the completion of the primary series of either vaccine, with a GMT (geometric mean titer) of 43.7 (95% CI: 23.2–82.4), followed by a dramatic decrease within 3 months. At Month 12, the GMT was 4.1 (95% CI: 3.8–4.4). Homologous boosting could restore humoral immunity, while heterologous boosting elicited around sixfold higher neutralization titers in comparison with homologous boosting. The effectiveness of receiving either vaccine against death and severe disease was around 85% for both shortly after the primary series. At Month 12, the protection against death did not decline, while the protection against severe disease decreased to ~75%. Conclusions: Both the BIBP-CorV and CoronaVac inactivated vaccines are safe. Sustained vaccine effectiveness against death was determined 12 months after the primary series, although protection against severe disease decreased slightly over time. A booster dose could strengthen the waning effectiveness; however, the duration of the incremental effectiveness and the additional benefit provided by a heterologous booster need to be studied. Full article

(This article belongs to the Special Issue SARS-CoV-2 Variants, Vaccines, and Immune Responses)

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