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Special Issue "Detection of SARS-CoV-2 Neutralizing Antibodies and Vaccine Development"

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

Deadline for manuscript submissions: 30 April 2024 | Viewed by 7843

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Special Issue Editor

Dr. Jianhui Nie

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Guest Editor

Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC), Beijing, China
Interests: SARS-CoV-2; HIV-1; HPV; vaccine development; vaccine evaluation; immune response; neutralizing antibody; standardization of assay

Special Issue Information

Dear Colleagues,

The COVID-19 pandemic has been ongoing for more than two years, killing more than 6.5 million people and having an unimaginable impact on people’s lives. Safe, effective, affordable and accessible vaccines are considered an important weapon to end the outbreak. Neutralizing antibodies are important indicators for the evaluation of the effectiveness of SARS-CoV-2 vaccines. Standardized in vitro potency methods are urgently needed to evaluate antiviral products in both pre-clinical and clinical phases. In addition, the detection of neutralizing antibodies against SARS-CoV-2 would be helpful to understand the status of the protective immune response among COVID-19 patients and asymptomatic cases. At present, there are many methods for detecting SARS-CoV-2 neutralizing antibodies, including culture live virus neutralization method, recombinant replication virus neutralization method, pseudotyped virus neutralization method, and competition inhibition neutralization antibody detection method. Even if the same type of method is used, specific operations in different laboratories can lead to differences in results. As a result, the neutralizing antibody test results of different vaccines are incomparable, meaning that the immunogenicity of different vaccines cannot be compared horizontally.

To achieve a more holistic understanding of recent scientific knowledge and current trends in SARS-CoV-2 neutralization assay and vaccine development, this Special issue is focused on the recent scientific and technical progresses made in this field. In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: (i) recent advances in novel neutralization assay development, (ii) standardization and comparison of different SARS-CoV-2 neutralization assays, (iii) comparison of neutralizing antibody responses induced by different vaccines, and (iv) correlates of protection.

I look forward to receiving your contributions.

Dr. Jianhui Nie
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

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

Published Papers (7 papers)

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Research

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Open AccessArticle

A Candidate DNA Vaccine Encoding the Native SARS-CoV-2 Spike Protein Induces Anti-Subdomain 1 Antibodies

Anders Frische

Vithiagaran Gunalan

Karen Angeliki Krogfelt

Anders Fomsgaard

and

Ria Lassaunière

Vaccines 2023, 11(9), 1451; https://doi.org/10.3390/vaccines11091451 - 03 Sep 2023

Viewed by 522

Abstract

The ideal vaccine against viral infections should elicit antibody responses that protect against divergent strains. Designing broadly protective vaccines against SARS-CoV-2 and other divergent viruses requires insight into the specific targets of cross-protective antibodies on the viral surface protein(s). However, unlike therapeutic monoclonal antibodies, the B-cell epitopes of vaccine-induced polyclonal antibody responses remain poorly defined. Here we show that, through the combination of neutralizing antibody functional responses with B-cell epitope mapping, it is possible to identify unique antibody targets associated with neutralization breadth. The polyclonal antibody profiles of SARS-CoV-2 index-strain-vaccinated rabbits that demonstrated a low, intermediate, or high neutralization efficiency of different SARS-CoV-2 variants of concern (VOCs) were distinctly different. Animals with an intermediate and high cross-neutralization of VOCs targeted fewer antigenic sites on the spike protein and targeted one particular epitope, subdomain 1 (SD1), situated outside the receptor binding domain (RBD). Our results indicate that a targeted functional antibody response and an additional focus on non-RBD epitopes could be effective for broad protection against different SARS-CoV-2 variants. We anticipate that the approach taken in this study can be applied to other viral vaccines for identifying future epitopes that confer cross-neutralizing antibody responses, and that our findings will inform a rational vaccine design for SARS-CoV-2. Full article

(This article belongs to the Special Issue Detection of SARS-CoV-2 Neutralizing Antibodies and Vaccine Development)

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Open AccessCommunication

Development of a Bioluminescent Imaging Mouse Model for SARS-CoV-2 Infection Based on a Pseudovirus System

and

Vaccines 2023, 11(7), 1133; https://doi.org/10.3390/vaccines11071133 - 22 Jun 2023

Viewed by 644

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains widely pandemic around the world. Animal models that are sensitive to the virus are therefore urgently needed to evaluate potential vaccines and antiviral agents; however, SARS-CoV-2 requires biosafety level 3 containment. To overcome this, we developed an animal model using the intranasal administration of SARS-CoV-2 pseudovirus. As the pseudovirus contains the firefly luciferase reporter gene, infected tissues and the viral load could be monitored by in vivo bioluminescent imaging. We used the model to evaluate the protective efficacy of monoclonal antibodies and the tissue tropism of different variants. The model may also be a useful tool for the safe and convenient preliminary evaluation of the protective efficacy of vaccine candidates against SARS-CoV-2, as well as the treatment efficacy of anti-viral drugs. Full article

(This article belongs to the Special Issue Detection of SARS-CoV-2 Neutralizing Antibodies and Vaccine Development)

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Open AccessArticle

The Quantification of Spike Proteins in the Inactivated SARS-CoV-2 Vaccines of the Prototype, Delta, and Omicron Variants by LC–MS

and

Vaccines 2023, 11(5), 1002; https://doi.org/10.3390/vaccines11051002 - 20 May 2023

Viewed by 843

Abstract

Developing variant vaccines or multivalent vaccines is a feasible way to address the epidemic as the SARS-CoV-2 variants of concern (VOCs) posed an increased risk to global public health. The spike protein of the SARS-CoV-2 virus was usually used as the main antigen in many types of vaccines to produce neutralizing antibodies against the virus. However, the spike (S) proteins of different variants were only differentiated by a few amino acids, making it difficult to obtain specific antibodies that can distinguish different VOCs, thereby challenging the accurate distinction and quantification of the variants using immunological methods such as ELISA. Here, we established a method based on LC–MS to quantify the S proteins in inactivated monovalent vaccines or trivalent vaccines (prototype, Delta, and Omicron strains). By analyzing the S protein sequences of the prototype, Delta, and Omicron strains, we identified peptides that were different and specific among the three strains and synthesized them as references. The synthetic peptides were isotopically labeled as internal targets. Quantitative analysis was performed by calculating the ratio between the reference and internal target. The verification results have shown that the method we established had good specificity, accuracy, and precision. This method can not only accurately quantify the inactivated monovalent vaccine but also could be applied to each strain in inactivated trivalent SARS-CoV-2 vaccines. Hence, the LC–MS method established in this study can be applied to the quality control of monovalent and multivalent SARS-CoV-2 variation vaccines. By enabling more accurate quantification, it will help to improve the protection of the vaccine to some extent. Full article

(This article belongs to the Special Issue Detection of SARS-CoV-2 Neutralizing Antibodies and Vaccine Development)

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Open AccessArticle

Clinical Characteristics of Mild Patients with Breakthrough Infection of Omicron Variant in China after Relaxing the Dynamic Zero COVID-19 Policy

and

Vaccines 2023, 11(5), 968; https://doi.org/10.3390/vaccines11050968 - 10 May 2023

Cited by 1 | Viewed by 629

Abstract

For SARS-CoV-2 mutants, the effectiveness of the COVID-19 vaccines is still controversial. In this study, we aimed to investigate the clinical characteristics of Omicron-infected patients who completed primary immunization and booster immunization, respectively, during the rapid propagation of the Omicron variant in China. A total of 932 patients with confirmed SARS-CoV-2 infection from 18 December 2022 to 1 January 2023 were included in this survey by filling out questionnaires online. The enrolled patients were divided into the primary immunization group and the booster immunization group according to their vaccination status. During the whole course of disease, the most frequent symptoms were fever (90.6%), cough (84.3%), weakness (77.4%), headache and dizziness (76.1%), and myalgia (73.9%). Nearly 90% of the patients had symptoms lasting for less than 10 days, and 39.8% of the patients ended the course of the disease in 4–6 days. A total of 58.8% of these patients had a fever with a maximum body temperature of over 38.5 °C. Moreover, 61.4% of the patients had a fever that lasted less than 2 days. There were no obvious differences in initial symptoms, cardinal symptoms, symptom duration time, maximum body temperature, and fever duration time between the two groups of patients. In addition, no significant difference was found in the positive or negative conversion time of SARS-CoV-2 antigen/nucleic acid between the two groups of patients. For mild patients with Omicron breakthrough infection, enhanced immunization has no significant impact on the clinical performance and duration of viral infection compared with primary immunization. The reasons behind the different clinical manifestations of patients with mild symptoms after the breakthrough infection of the Omicron strain are still worth further research. Heterologous vaccination may be a better strategy for enhanced immunization, which can help improve the immune protection ability of the population. Further research should be carried out on vaccines against mutant strains and spectral anti-COVID-19 vaccines. Full article

(This article belongs to the Special Issue Detection of SARS-CoV-2 Neutralizing Antibodies and Vaccine Development)

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Open AccessArticle

Heterologous Vector—mRNA Based SARS-CoV-2 Vaccination Strategy Appears Superior to a Homologous Vector—Based Vaccination Scheme in German Healthcare Workers Regarding Humoral SARS-CoV-2 Response Indicating a High Boosting Effect by mRNA Vaccines

and

Vaccines 2023, 11(3), 701; https://doi.org/10.3390/vaccines11030701 - 19 Mar 2023

Viewed by 1180

Abstract

Background: Longitudinal humoral SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) immunity for up to 15 months due to vaccination, the efficacy of vaccination strategies (homologous, vector–vector versus heterologous, vector–mRNA), the influence of vaccination side effects, and the infection rate in German healthcare workers need to be investigated. Methods: In this study, 103 individuals vaccinated against SARS-CoV-2 were enrolled to examine their anti-SARS-CoV-2 anti-N- and anti-RBD/S1-Ig levels. A total of 415 blood samples in lithium heparin tubes were prospectively obtained, and a structured survey regarding medical history, type of vaccine, and vaccination reactions was conducted. Results: All participants demonstrated a humoral immune response, among whom no values decreased below the positivity cutoff. Five to six months after the third vaccination, three participants showed anti-RBD/S1 antibodies of less than 1000 U/mL. We observed higher levels for heterologous mRNA-/vector-based combinations compared to pure vector-based vaccination after the second vaccination, which is harmonized after a third vaccination with the mRNA-vaccine only in both cohorts. The incidence of vaccine breakthrough in a highly exposed cohort was 60.3%. Conclusion: Sustained long-term humoral immunity was observed, indicating the superiority of a heterologous mRNA-/vector-based combination compared to pure vector-based vaccination. There was longevity of anti-RBD/S1 antibodies of at least 4 and up to 7 months without external stimulus. Regarding vaccination reactogenity, the occurrence of local symptoms as pain at the injection site was increased after the first mRNA application compared to the vector–vector cohort with a general decrease in adverse events at later vaccination time points. Overall, a correlation between the humoral vaccination response and vaccination side effects was not observed. Despite the high prevalence of vaccine breakthroughs, these only occurred in the later course of the study when more infectious variants, which are, however, associated with milder courses, were present. These results provide insights into vaccine-related serologic responses, and the study should be expanded using additional vaccine doses and novel variants in the future. Full article

(This article belongs to the Special Issue Detection of SARS-CoV-2 Neutralizing Antibodies and Vaccine Development)

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Open AccessArticle

Rapid Quantification of SARS-CoV-2 Neutralising Antibodies Using Time-Resolved Fluorescence Immunoassay

and

Vaccines 2022, 10(12), 2149; https://doi.org/10.3390/vaccines10122149 - 15 Dec 2022

Cited by 1 | Viewed by 1303

Abstract

The quantification of neutralising antibodies (NAb) for SARS-CoV-2 has become an important tool for monitoring protective immunity following infection or immunisation. In this study, we evaluated using World-Health-Organisation-standard immunoglobulin preparations, a novel point-of-care test that quantitates NAb by time-resolved fluorescent immunoassay. The assay provided robust data of binding antibody units (BAU) in 15 min that were well correlated with NAb values obtained by traditional in vitro neutralisation assay. The data also correlated well to spike-receptor-binding domain-binding antibodies over a broad range of plasma dilutions. The assay was extremely sensitive, able to detect positive samples after dilution 1:10,000 and over a wide range of BAU. Assay specificity was estimated at 96% using Pre-COVID-19 serum samples when applying a cut-off value of 47 BAU/mL, although readings of up to 100 BAU/mL could be considered borderline. This point-of-care diagnostic test is useful for rapid population screening and includes the use of capillary blood samples. Furthermore, it provides results for SARS-CoV-2 NAb in 15 min, which can inform immediate decisions regarding protective immunity levels and the need for continued COVID immunisations. Full article

(This article belongs to the Special Issue Detection of SARS-CoV-2 Neutralizing Antibodies and Vaccine Development)

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Review

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Open AccessReview

A Clinical Insight on New Discovered Molecules and Repurposed Drugs for the Treatment of COVID-19

and

Vaccines 2023, 11(2), 332; https://doi.org/10.3390/vaccines11020332 - 01 Feb 2023

Cited by 2 | Viewed by 2036

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began churning out incredulous terror in December 2019. Within several months from its first detection in Wuhan, SARS-CoV-2 spread to the rest of the world through droplet infection, making it a pandemic situation and a healthcare emergency across the globe. The available treatment of COVID-19 was only symptomatic as the disease was new and no approved drug or vaccine was available. Another challenge with COVID-19 was the continuous mutation of the SARS-CoV-2 virus. Some repurposed drugs, such as hydroxychloroquine, chloroquine, and remdesivir, received emergency use authorization in various countries, but their clinical use is compromised with either severe and fatal adverse effects or nonavailability of sufficient clinical data. Molnupiravir was the first molecule approved for the treatment of COVID-19, followed by Paxlovid™, monoclonal antibodies (MAbs), and others. New molecules have variable therapeutic efficacy against different variants or strains of SARS-CoV-2, which require further investigations. The aim of this review is to provide in-depth information on new molecules and repurposed drugs with emphasis on their general description, mechanism of action (MOA), correlates of protection, dose and dosage form, route of administration, clinical trials, regulatory approval, and marketing authorizations. Full article

(This article belongs to the Special Issue Detection of SARS-CoV-2 Neutralizing Antibodies and Vaccine Development)

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