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Vaccines
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COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition
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COVID Vaccines: Design, Development, and Immune Response Studies: 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: 30 April 2025 | Viewed by 11598

Special Issue Editors

Dr. Fabrizio Maggi

E-Mail Website
Guest Editor
Department of Medicine and Surgery, University of Insubria, 21100 Varese, Italy
Interests: sars-cov-2; HIV
Special Issues, Collections and Topics in MDPI journals
Dr. Licia Bordi

E-Mail Website
Guest Editor
Laboratory of Virology, National Institute for Infectious Diseases "L. Spallanzani", Via Portuense 292, 00149 Rome, Italy
Interests: rapid tests for COVID-19; saliva and COVID-19 diagnosis; emerging viruses; host–pathogen interaction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

COVID-19 vaccines represented an unprecedented effort to contain the pandemic. Developed in record time, they have saved millions of lives over the past few years. Nevertheless, there is still room for improvement on different fronts, ranging from the elicitation of mucosal immunity and the prevention of transmission to their ability to elicit greater immune responses in immunocompromised patients. While it is currently not clear whether yearly boosts will continue to be required, multivalent vaccines based on updated versions of the Spike protein are under development, as well as vaccines based on SARS-CoV-2 antigens other than Spike and combination vaccines with flu and pneumococcus. In this Special Issue, we welcome original research and systematic reviews on vaccine design, immune responses, and different boosting protocols.

Dr. Fabrizio Maggi
Dr. Licia Bordi
Guest Editors

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 vaccine
  • mucosal immunity
  • immune response
  • SARS-CoV-2
  • vaccine design

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Related Special Issue

Published Papers (6 papers)

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Research

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14 pages, 1260 KiB  
Article
Incidence of SARS-CoV-2 Infection Among European Healthcare Workers and Effectiveness of the First Booster COVID-19 Vaccine, VEBIS HCW Observational Cohort Study, May 2021–May 2023
by Camelia Savulescu, Albert Prats-Uribe, Kim Brolin, Zvjezdana Lovrić Makarić, Anneli Uusküla, Georgios Panagiotakopoulos, Colm Bergin, Catherine Fleming, Antonella Agodi, Paolo Bonfanti, Rita Murri, Viesturs Zvirbulis, Dace Zavadska, Konstanty Szuldrzynski, Ausenda Machado, Corneliu Petru Popescu, Mihai Craiu, Maria Cisneros, Miriam Latorre-Millán, Goranka Petrović, Liis Lohur, Kyriaki Tryfinopoulou, Jonathan McGrath, Lauren Ferguson, Martina Barchitta, Anna Spolti, Katleen de Gaetano Donati, Ilze Abolina, Dagne Gravele, Vânia Gaio, Simin Aysel Florescu, Mihaela Lazar, Pilar Subirats, Laura Clusa Cuesta, Gordan Sarajlić, Marina Amerali, Jacklyn Sui, Claire Kenny, Venerando Rapisarda, Marianna Rossi, Silvia Lamonica, Dainis Krievins, Elza Anna Barzdina, Ana Palmira Amaral, Alma Gabriela Kosa, Victor Daniel Miron, Carmen Muñoz-Almagro, Ana María Milagro, Sabrina Bacci, Piotr Kramarz, Anthony Nardone and the VEBIS HCW VE Study Groupadd Show full author list remove Hide full author list
Vaccines 2024, 12(11), 1295; https://doi.org/10.3390/vaccines12111295 - 19 Nov 2024
Viewed by 479
Abstract
Background: European countries have included healthcare workers (HCWs) among priority groups for COVID-19 vaccination. We established a multi-country hospital network to measure the SARS-CoV-2 incidence and effectiveness of COVID-19 vaccines among HCWs against laboratory-confirmed SARS-CoV-2 infection. Methods: HCWs from 19 hospitals in 10 [...] Read more.
Background: European countries have included healthcare workers (HCWs) among priority groups for COVID-19 vaccination. We established a multi-country hospital network to measure the SARS-CoV-2 incidence and effectiveness of COVID-19 vaccines among HCWs against laboratory-confirmed SARS-CoV-2 infection. Methods: HCWs from 19 hospitals in 10 countries participated in a dynamic prospective cohort study, providing samples for SARS-CoV-2 testing at enrolment and during weekly/fortnightly follow-up. We measured the incidence during pre-Delta (2 May–6 September 2021), Delta (7 September–14 December 2021), and Omicron (15 December 2021–2 May 2023) waves. Using Cox regression, we measured the relative vaccine effectiveness (rVE) of the first COVID-19 booster dose versus primary course alone during Delta and Omicron waves. Results: We included a total of 3015 HCWs. Participants were mostly female (2306; 79%), with a clinical role (2047; 68%), and had a median age of 44 years. The overall incidence of SARS-CoV-2 infection was 3.01/10,000 person-days during pre-Delta, 4.21/10,000 during Delta, and 23.20/10,000 during Omicron waves. rVE was 59% (95% CI: −25; 86) during Delta and 22% (1; 39) during Omicron waves. rVE was 51% (30; 65) 7–90 days after the first booster dose during the Omicron wave. Conclusions: The incidence of SARS-CoV-2 infection among HCWs was higher during the Omicron circulation period. The first COVID-19 vaccine booster provided additional protection against SARS-CoV-2 infection compared to primary course vaccination when recently vaccinated <90 days. This multi-country HCW cohort study addressing infection as the main outcome is crucial for informing public health interventions for HCWs. Full article
(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)
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25 pages, 9144 KiB  
Article
Safety and Immunogenicity Study of a Bivalent Vaccine for Combined Prophylaxis of COVID-19 and Influenza in Non-Human Primates
by Ekaterina Stepanova, Irina Isakova-Sivak, Victoria Matyushenko, Daria Mezhenskaya, Igor Kudryavtsev, Arina Kostromitina, Anna Chistiakova, Alexandra Rak, Ekaterina Bazhenova, Polina Prokopenko, Tatiana Kotomina, Svetlana Donina, Vlada Novitskaya, Konstantin Sivak, Dzhina Karal-Ogly and Larisa Rudenko
Vaccines 2024, 12(10), 1099; https://doi.org/10.3390/vaccines12101099 - 26 Sep 2024
Viewed by 3627
Abstract
Background. Influenza and SARS-CoV-2 viruses are two highly variable pathogens. We have developed a candidate bivalent live vaccine based on the strain of licensed A/Leningrad/17-based cold-adapted live attenuated influenza vaccine (LAIV) of H3N2 subtype, which expressed SARS-CoV-2 immunogenic T-cell epitopes. A cassette encoding [...] Read more.
Background. Influenza and SARS-CoV-2 viruses are two highly variable pathogens. We have developed a candidate bivalent live vaccine based on the strain of licensed A/Leningrad/17-based cold-adapted live attenuated influenza vaccine (LAIV) of H3N2 subtype, which expressed SARS-CoV-2 immunogenic T-cell epitopes. A cassette encoding fragments of S and N proteins of SARS-CoV-2 was inserted into the influenza NA gene using the P2A autocleavage site. In this study, we present the results of preclinical evaluation of the developed bivalent vaccine in a non-human primate model. Methods. Rhesus macaques (Macaca mulatta) (n = 3 per group) were immunized intranasally with 7.5 lg EID50 of the LAIV/CoV-2 bivalent vaccine, a control non-modified H3N2 LAIV or a placebo (chorioallantoic fluid) using a sprayer device, twice, with a 28-day interval. The blood samples were collected at days 0, 3, 28 and 35 for hematological and biochemical assessment. Safety was also assessed by monitoring body weight, body temperature and clinical signs of the disease. Immune responses to influenza virus were assessed both by determining serum antibody titers in hemagglutination inhibition assay, microneutralization assay and IgG ELISA. T-cell responses were measured both to influenza and SARS-CoV-2 antigens using ELISPOT and flow cytometry. Three weeks after the second immunization, animals were challenged with 105 PFU of Delta SARS-CoV-2. The body temperature, weight and challenge virus shedding were monitored for 5 days post-challenge. In addition, virus titers in various organs and histopathology were evaluated on day 6 after SARS-CoV-2 infection. Results. There was no toxic effect of the immunizations on the hematological and coagulation hemostasis of animals. No difference in the dynamics of the average weight and thermometry results were found between the groups of animals. Both LAIV and LAIV/CoV-2 variants poorly replicated in the upper respiratory tract of rhesus macaques. Nevertheless, despite this low level of virus shedding, influenza-specific serum IgG responses were detected in the group of monkeys immunized with the LAIV/CoV-2 bivalent but not in the LAIV group. Furthermore, T-cell responses to both influenza and SARS-CoV-2 viruses were detected in the LAIV/CoV-2 vaccine group only. The animals were generally resistant to SARS-CoV-2 challenge, with minimal virus shedding in the placebo and LAIV groups. Histopathological changes in vaccinated animals were decreased compared to the PBS group, suggesting a protective effect of the chimeric vaccine candidate. Conclusions. The candidate bivalent vaccine was safe and immunogenic for non-human primates and warrants its further evaluation in clinical trials. Full article
(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)
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17 pages, 4076 KiB  
Article
Immunogenicity and Protective Efficacy of Baculovirus-Expressed SARS-CoV-2 Envelope Protein in Mice as a Universal Vaccine Candidate
by Tuba Çiğdem Oğuzoğlu, Alireza Hanifehnezhad, Saber Delpasand Khabbazi, İlke Karayel-Hacıoğlu, Onur Kaynarcalıdan, Zehra Fırat, Nazlıcan Filazi, Eda Erdem-Şahinkesen, Buket Gül, Muhammed Cesim Karabulut, Enes Koba, Ece Adıgüzel, Elif İrem Şenlik, Emrah Korkulu, Cansu Demirden, İlker Şahinkesen, Ahmet Ceylan, Hacer Muratoğlu, Sevil Vural, Zihni Demirbağ and Aykut Özkuladd Show full author list remove Hide full author list
Vaccines 2024, 12(9), 977; https://doi.org/10.3390/vaccines12090977 - 28 Aug 2024
Viewed by 4015
Abstract
The envelope (env) protein of SARS-CoV-2, a pivotal component of the viral architecture, plays a multifaceted role in viral assembly, replication, pathogenesis, and ion channel activity. These features make it a significant target for understanding virus–host interactions and developing vaccines to combat COVID-19. [...] Read more.
The envelope (env) protein of SARS-CoV-2, a pivotal component of the viral architecture, plays a multifaceted role in viral assembly, replication, pathogenesis, and ion channel activity. These features make it a significant target for understanding virus–host interactions and developing vaccines to combat COVID-19. Recent structural studies provide valuable insights into the conformational dynamics and membrane topology of the SARS-CoV-2 env protein, shedding light on its functional mechanisms. The strong homology and highly conserved structure of the SARS-CoV-2 env protein shape its immunogenicity and functional characteristics. This study examines the ability of the recombinant SARS-CoV-2 env protein to stimulate an immune response. In this study, recombinant envelope proteins were produced using the baculovirus expression system, and their potential efficacy was evaluated in both in vivo and in vitro models. Our results reveal that the env protein of SARS-CoV-2 stimulates humoral and cellular responses and highlight its potential as a promising vaccine candidate for combating the ongoing pandemic. Full article
(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)
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13 pages, 2286 KiB  
Article
Boost and Increased Antibody Breadth Following a Second Dose of PARVAX for SARS-CoV-2 in Mice and Nonhuman Primates
by Urja Bhatt, Cecile Herate, Reynette Estelien, Francis Relouzat, Nathalie Dereuddre-Bosquet, Dawid Maciorowski, Cheikh Diop, Emma Couto, Jillian Staiti, Mariangela Cavarelli, Laëtitia Bossevot, Quentin Sconosciuti, Page Bouchard, Roger Le Grand, Luk H. Vandenberghe and Nerea Zabaleta
Vaccines 2024, 12(8), 882; https://doi.org/10.3390/vaccines12080882 - 2 Aug 2024
Viewed by 1004
Abstract
PARVAX is a genetic vaccine platform based on an adeno-associated vector that has demonstrated to elicit potent, durable, and protective immunity in nonhuman primates (NHPs) after a single dose. Here, we assessed vaccine immunogenicity following a PARVAX prime-boost regimen against SARS-CoV-2. In mice, [...] Read more.
PARVAX is a genetic vaccine platform based on an adeno-associated vector that has demonstrated to elicit potent, durable, and protective immunity in nonhuman primates (NHPs) after a single dose. Here, we assessed vaccine immunogenicity following a PARVAX prime-boost regimen against SARS-CoV-2. In mice, a low-dose prime followed by a higher-dose boost elicited potent neutralizing antibody responses and distinct cross-reactivity profiles, depending on the antigen used in the booster vaccine. However, the potent neutralizing anti-vector antibody responses developed in mice limited the dose that could be administered as a prime. We further explored the re-administration efficacy in NHPs primed with a SARS-CoV-2 Delta vaccine and boosted with an Omicron BA.1 vaccine at week 15, after the primary response peak antibody levels were reached. The boost elicited an increase in antibodies against several Omicron variants, but no increase was detected in the antibody titers for other variants. The anti-vector responses were low and showed some increased subsequent boosts but generally declined over time. The potent prime vaccination limited the detection of the boosting effect, and therefore, the effect of anti-vector immunity was not fully elucidated. These data show that PARVAX can be effectively re-administered and induce a novel antigenic response. Full article
(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)
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Review

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18 pages, 7626 KiB  
Review
Subsequent Waves of Convergent Evolution in SARS-CoV-2 Genes and Proteins
by Daniele Focosi, Pietro Giorgio Spezia and Fabrizio Maggi
Vaccines 2024, 12(8), 887; https://doi.org/10.3390/vaccines12080887 - 5 Aug 2024
Cited by 1 | Viewed by 1351
Abstract
Beginning in 2022, following widespread infection and vaccination among the global population, the SARS-CoV-2 virus mainly evolved to evade immunity derived from vaccines and past infections. This review covers the convergent evolution of structural, nonstructural, and accessory proteins in SARS-CoV-2, with a specific [...] Read more.
Beginning in 2022, following widespread infection and vaccination among the global population, the SARS-CoV-2 virus mainly evolved to evade immunity derived from vaccines and past infections. This review covers the convergent evolution of structural, nonstructural, and accessory proteins in SARS-CoV-2, with a specific look at common mutations found in long-lasting infections that hint at the virus potentially reverting to an enteric sarbecovirus type. Full article
(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)
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Other

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12 pages, 1538 KiB  
Brief Report
STAR LIGHT Study: XBB.1.5 COVID-19 mRNA Vaccines Boost Systemic but Not Mucosal Immunity Against the SARS-CoV-2 JN.1 Variant in Patients with Chronic Liver Disease
by Simon Woelfel, Daniel Junker, Irina Bergamin, Pamela Meyer-Herbon, Roman Stillhard, Nicole Graf, Georg Leinenkugel, Joel Dütschler, Marius König, Livia Kammerlander, Rahel Häuptle, Sarah Zwyssig, Claudia Krieger, Samuel Truniger, Seraina Koller, Katline Metzger-Peter, Nicola Frei, STAR SIGN Study Investigators, Werner C. Albrich, Matthias Friedrich, Christine Bernsmeier, Jan Hendrik Niess, Wolfgang Korte, Justus J. Bürgi, Alex Dulovic, Nicole Schneiderhan-Marra, David Semela and Stephan Brandadd Show full author list remove Hide full author list
Vaccines 2024, 12(11), 1241; https://doi.org/10.3390/vaccines12111241 - 31 Oct 2024
Viewed by 649
Abstract
Background: Patients with chronic liver disease (CLD) have impaired vaccine immunogenicity and an excess risk of severe COVID-19. While variant-adapted COVID-19 mRNA vaccines are recommended for vulnerable individuals, their efficacy in patients with CLD has not been studied. Methods: We present the first [...] Read more.
Background: Patients with chronic liver disease (CLD) have impaired vaccine immunogenicity and an excess risk of severe COVID-19. While variant-adapted COVID-19 mRNA vaccines are recommended for vulnerable individuals, their efficacy in patients with CLD has not been studied. Methods: We present the first evaluation of XBB.1.5 COVID-19 vaccine immunogenicity against the SARS-CoV-2 JN.1 variant in patients with CLD. Serum anti-receptor binding domain (RBD) IgG, neutralization, and saliva anti-RBD IgG and IgA against wild-type SARS-CoV-2 (WT) and the XBB.1.5, EG.5.1, BA.2.86, and JN.1 variants were quantified before and 2–4 weeks following a fourth dose of XBB.1.5 mRNA vaccines. Results: Vaccination boosted anti-RBD IgG and neutralization against all tested variants including JN.1 (each p < 0.001). Following immunization, neutralization was lower against JN.1 compared to WT, XBB.1.5, and EG.5.1 (p < 0.001, p < 0.001, and p < 0.01, respectively). Vaccination reduced neutralization failure rates against BA.2.86 and JN.1 (each p < 0.05). The evasion of vaccine-induced antibodies by the tested variants was low, indicated by the positive correlation between anti-RBD IgG and neutralization. At mucosal sites, vaccination boosted anti-RBD IgG (each p < 0.01) but failed to induce infection-blocking IgA (each p > 0.05). Conclusion: XBB.1.5 vaccines protect CLD patients against recent SARS-CoV-2 variants, but developing vaccines with optimized mucosal immunogenicity is required to prevent SARS-CoV-2 transmission and recurrent seasonal COVID-19 outbreaks. Full article
(This article belongs to the Special Issue COVID Vaccines: Design, Development, and Immune Response Studies: 2nd Edition)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Dear Colleagues,

COVID-19 vaccines represented an unprecedented effort to contain the pandemic. Developed in record time, they have saved millions of lives over the past few years. Nevertheless, there is still room for improvement on different fronts, ranging from the elicitation of mucosal immunity and the prevention of transmission to their ability to elicit greater immune responses in immunocompromised patients. While it is currently not clear whether yearly boosts will continue to be required, multivalent vaccines based on updated versions of the Spike protein are under development, as well as vaccines based on SARS-CoV-2 antigens other than Spike and combination vaccines with flu and pneumococcus. In this Special Issue, we welcome original research and systematic reviews on vaccine design, immune responses, and different boosting protocols.

Dr. Fabrizio Maggi
Dr. Licia Bordi
Guest Editors

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