Detection of SARS-CoV-2 Neutralizing Antibodies and Vaccine Development: 2nd Edition

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "COVID-19 Vaccines and Vaccination".

Deadline for manuscript submissions: closed (31 March 2025) | Viewed by 2854

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Guest Editor
Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing 102629, China
Interests: SARS-CoV-2; HIV-1; HPV; vaccine development; vaccine evaluation; immune response; neutralizing antibody; standardization of assay
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Special Issue Information

Dear Colleagues,

The COVID-19 pandemic has been ongoing for more than four years, claiming the lives of over 7 million people and significantly impacting the lives of many. Vaccines are seen as a crucial tool in ending the outbreak, and it is important to have safe, effective, affordable, and accessible vaccines. Neutralizing antibodies play a key role in evaluating the effectiveness of SARS-CoV-2 vaccines. There is an urgent need for standardized in vitro potency methods to assess antiviral products in both pre-clinical and clinical phases. Detecting neutralizing antibodies against SARS-CoV-2 can help understand the protective immune response in COVID-19 patients and asymptomatic cases. Currently, there are various methods for detecting SARS-CoV-2 neutralizing antibodies, but differences in laboratory procedures can lead to incomparable results. This makes it difficult to compare the immunogenicity of different vaccines. To gain a better understanding of recent scientific knowledge and current trends in SARS-CoV-2 neutralization assay and vaccine development, this Special Issue focuses on recent scientific and technical progress in this field. This Special Issue welcomes original research articles and reviews covering recent advances in novel neutralization assay development, standardization and comparison of different SARS-CoV-2 neutralization assays, comparison of neutralizing antibody responses induced by different vaccines, and correlates of protection.

I look forward to receiving your contributions.

Dr. Jianhui Nie
Guest Editor

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Keywords

  • COVID-19
  • SARS-CoV-2
  • vaccine
  • neutralizing antibody
  • correlation of protection
  • standardization

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Related Special Issue

Published Papers (3 papers)

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Research

22 pages, 5356 KiB  
Article
Mucosal and Serum Neutralization Immune Responses Elicited by COVID-19 mRNA Vaccination in Vaccinated and Breakthrough-Infection Individuals: A Longitudinal Study from Louisville Cohort
by Lalit Batra, Divyasha Saxena, Triparna Poddar, Maryam Zahin, Alok Amraotkar, Megan M. Bezold, Kathleen T. Kitterman, Kailyn A. Deitz, Amanda B. Lasnik, Rachel J. Keith, Aruni Bhatnagar, Maiying Kong, Jon D. Gabbard, William E. Severson and Kenneth E. Palmer
Vaccines 2025, 13(6), 559; https://doi.org/10.3390/vaccines13060559 - 24 May 2025
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Abstract
Background/Objectives: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), has resulted in 777 million cases worldwide. Various vaccines have been approved to control the spread of COVID-19, with mRNA vaccines (Pfizer and Moderna) being widely used in the [...] Read more.
Background/Objectives: The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), has resulted in 777 million cases worldwide. Various vaccines have been approved to control the spread of COVID-19, with mRNA vaccines (Pfizer and Moderna) being widely used in the USA. We conducted a prospective longitudinal study to analyze the immune response elicited by two/three and four doses of monovalent mRNA vaccines in both vaccinated individuals and those who experienced breakthrough infections. Participants were stratified into different age groups: 18–40, 41–60, and over 60 years. Methods: We assessed cross-variant neutralization responses in two cohorts—Cohort I: n = 167 (serum), Cohort II: n = 92 (serum and nasal swab) samples—using infectious virus microneutralization assay (MN) and antibody (IgG or IgA) binding ELISA titers to the spike protein receptor binding domain (RBD). Samples were collected from the Louisville Metro–Jefferson County Co-Immunity Project, a federally funded, population-based study for the surveillance of SARS-CoV-2 in Jefferson County, Kentucky during 2020–2022, involving both health care workers and a local community. Results: Individuals who received two doses of the mRNA vaccine exhibited reduced neutralization against Beta, Delta, and Omicron BA.1 variants compared to wildtype Wuhan, with further decline observed six months post-booster vaccination. However, individuals who experienced natural COVID-19 infection (breakthrough) after receiving two vaccine doses showed enhanced neutralization and antibody responses, particularly against Omicron BA.1. Following the 3rd dose, antibodies and neutralization responses were restored. Among triple-vaccinated individuals, reduced neutralization was observed against Omicron variants BA.1, BA.5, and BA.2 compared to Wuhan. Neutralization responses were better against BA.2 variant compared to BA.1 and BA.5. However, individuals who received three doses of vaccine and experienced a breakthrough infection (n = 45) elicited significantly higher neutralizing antibodies responses against all Omicron subvariants compared to vaccinated individuals. Interestingly, nasal swab samples collected from volunteers with breakthrough infection showed significantly elevated spike-reactive mucosal IgA antibodies and enhanced cross neutralization against BA.1, BA.2, and BA.5 compared to individuals who received only three vaccine doses. Conclusions: mRNA vaccination elicits a strong systemic immune response by boosting serum neutralizing antibodies (NAb), although this protection wanes over time, allowing new variants to escape neutralization. Breakthrough individuals have extra enrichment in nasal NAb offering protection against emerging variants. This longitudinal immune profiling underscores the strengthening of pandemic preparedness and supports the development of durable mucosal vaccines against respiratory infectious disease. Full article
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17 pages, 1808 KiB  
Article
Impact of B18R-Encoding Messenger Ribonucleic Acid Co-Delivery on Neutralizing Antibody Production in Self-Amplifying Messenger Ribonucleic Acid Vaccines
by Yutao Wang, Lei Li, Min Liang, Gan Liu and Yinying Lu
Vaccines 2025, 13(5), 537; https://doi.org/10.3390/vaccines13050537 - 18 May 2025
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Abstract
Objectives: The COVID-19 pandemic has brought mRNA vaccines to the forefront due to their widespread use. In this study, we explored the potential advantages of the self-amplifying mRNA (saRNA) vaccine over conventional mRNA vaccines. Methods: Initially, we optimized lipid nanoparticle formulations [...] Read more.
Objectives: The COVID-19 pandemic has brought mRNA vaccines to the forefront due to their widespread use. In this study, we explored the potential advantages of the self-amplifying mRNA (saRNA) vaccine over conventional mRNA vaccines. Methods: Initially, we optimized lipid nanoparticle formulations and employed dT20 affinity chromatography purification to improve the intracellular expression of saRNA. Subsequently, we demonstrated that saRNA exhibited sustained expression for up to one month, both in vitro and in vivo, in contrast to mRNA. Finally, we developed a saRNA-based COVID-19 vaccine and achieved superior immune protection in mice compared to mRNA vaccine by co-delivering the B18R-encoding mRNA. Results: The co-delivery of B18R-mRNA with the saRNA vaccine significantly enhanced neutralizing antibody responses, outperforming those induced by the mRNA vaccine alone. This co-delivery strategy effectively regulated the early innate immune activation triggered by saRNA, facilitating a more robust adaptive immune response. Conclusions: The optimization strategies we used in this study highlight the potential of saRNA vaccines to offer stronger and more durable immune protection. The insights gained from this study not only promote the advancement of saRNA vaccine development but also provide practical guidance for their broader application in the fight against infectious diseases. Full article
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18 pages, 1949 KiB  
Article
Antibody Responses to mRNA COVID-19 Vaccine Among Healthcare Workers in Outpatient Clinics in Japan
by Teruhime Otoguro, Keita Wagatsuma, Toshiharu Hino, The Society of Ambulatory and General Pediatrics of Japan, Yusuke Ichikawa, Tri Bayu Purnama, Yuyang Sun, Jiaming Li, Irina Chon, Hisami Watanabe and Reiko Saito
Vaccines 2025, 13(1), 90; https://doi.org/10.3390/vaccines13010090 - 18 Jan 2025
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Abstract
Background: This study aimed to assess the antibody response to SARS-CoV-2 vaccines among healthcare workers (HCWs) from multiple outpatient clinics in Japan, examining the effects of baseline characteristics (e.g., sex, age, underlying condition, smoking history, occupation) and prior infections. Methods: A total of [...] Read more.
Background: This study aimed to assess the antibody response to SARS-CoV-2 vaccines among healthcare workers (HCWs) from multiple outpatient clinics in Japan, examining the effects of baseline characteristics (e.g., sex, age, underlying condition, smoking history, occupation) and prior infections. Methods: A total of 101 HCWs provided serum at four time points between October 2020 and July 2023. HCWs received two to six doses of mRNA vaccine (BNT162b2 or mRNA-1273). Anti-nucleocapsid (N) and anti-spike (S) IgG antibodies against the ancestral Wuhan strain were measured using the Abbott Architect™ SARS-CoV-2 IgG assay. Univariate and regression analysis evaluated factors such as past infections, age, sex, smoking, underlying condition, and occupation. Results: After four to six doses, the median anti-S IgG titer in uninfected HCWs was 1807.30 BAU/mL, compared to 1899.89 BAU/mL in HCWs with prior infections. The median anti-N IgG titer was 0.10 index S/C in uninfected HCWs and 0.39 index S/C in infected HCWs. HCWs with prior infection had anti-S IgG titers 1.1 to 5.8 times higher than those without. Univariate and multivariate analyses indicated infection and vaccination significantly increased anti-S and anti-N IgG titers. Age, sex, smoking history and occupation did not influence antibody titers while underlying conditions were associated with lower anti-N IgG titers. Conclusions: Infection and vaccination were strongly associated with an increase in anti-S and anti-N IgG titers; however, the impact of hybrid immunity appeared to be limited and varied depending on the timing of the sampling. These findings provide valuable insights for developing personalized vaccination strategies and future vaccine development. Full article
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