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COVID-19 Vaccine Candidate 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: closed (31 March 2023) | Viewed by 25083

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Special Issue Editors

Dr. Rafael Blasco

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Guest Editor

Departamento de Biotecnología, INIA CSIC, Ctra. La Coruña km 7.5, E-28040 Madrid, Spain
Interests: poxviruses; vaccinia virus; recombinant vaccines; virus glycoproteins; virus genetics

Dr. Javier Ortego

E-Mail Website
Guest Editor

Centro de Investigación en Sanidad Animal INIA CSIC, Valdeolmos- Alalpardo, Carretera de Algete a El Casar, Km 8, E-28040 Madrid, Spain
Interests: bluetongue virus; viral infectious diseases; zoonosis; vaccine development; viral immunology

Dr. Alejandro Marin-Lopez

E-Mail Website
Co-Guest Editor

Department of Internal Medicine, Section of Infectious Diseases, School of Medicine, Yale University, New Haven, CT, USA
Interests: infectious pathogens; arbovirus; vaccination
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The COVID-19 pandemic has revealed the need for an advanced vaccine pipeline to better deal with emerging diseases. Beyond the current situation and the approved vaccines, the necessities ahead, derived from human population diversity, virus evolution and the epidemiological situation, are uncertain. Fortunately, expanded technological possibilities in the field of vaccine generation are available, including established and new strategies. Vaccine qualities such as speed of generation, coding capacity, potency and safety must be considered when science is challenged with the task of developing new vaccines. Even though basic vaccination needs can be met with current COVID-19 vaccines, it is clear that the emergence of new variants, changes in virus pathogenicity or transmissibility and diversity in immunization scenarios and social constraints may require additional vaccine formulations. Of particular importance is the breadth of protection in light of virus diversity and the duration of such protection. In light of the considerable amount of work carried out in the field of vaccine technologies over the last years, much is to be learnt from the recent experiences of many research groups in vaccine design and testing, which may constitute a valuable resource for the future.

We are pleased to invite you to contribute to this Special Issue of Vaccines, entitled “COVID-19 vaccine candidate development”.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: COVID-19 candidate vaccine design, construction and trials, and refinements or innovations regarding vaccine testing, both in animal models and in human clinical trials.

Dr. Rafael Blasco
Dr. Javier Ortego
Dr. Alejandro Marin-Lopez
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

vaccine
COVID-19
coronaviruses
humoral immune response
adaptive immune response
immunological memory
vaccine testing
recombinant vaccines
animal models

Published Papers (9 papers)

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Research

Jump to: Review

24 pages, 5471 KiB

Open AccessArticle

Vaccinia Virus Strain MVA Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Glycoprotein Induces Robust Protection and Prevents Brain Infection in Mouse and Hamster Models

by María M. Lorenzo, Alejandro Marín-López, Kevin Chiem, Luis Jimenez-Cabello, Irfan Ullah, Sergio Utrilla-Trigo, Eva Calvo-Pinilla, Gema Lorenzo, Sandra Moreno, Chengjin Ye, Jun-Gyu Park, Alejandro Matía, Alejandro Brun, Juana M. Sánchez-Puig, Aitor Nogales, Walther Mothes, Pradeep D. Uchil, Priti Kumar, Javier Ortego, Erol Fikrig, Luis Martinez-Sobrido and Rafael Blasco Show full author list Hide full author list

Vaccines 2023, 11(5), 1006; https://doi.org/10.3390/vaccines11051006 - 21 May 2023

Cited by 3 | Viewed by 2250

Abstract

The COVID-19 pandemic has underscored the importance of swift responses and the necessity of dependable technologies for vaccine development. Our team previously developed a fast cloning system for the modified vaccinia virus Ankara (MVA) vaccine platform. In this study, we reported on the construction and preclinical testing of a recombinant MVA vaccine obtained using this system. We obtained recombinant MVA expressing the unmodified full-length SARS-CoV-2 spike (S) protein containing the D614G amino-acid substitution (MVA-Sdg) and a version expressing a modified S protein containing amino-acid substitutions designed to stabilize the protein a in a pre-fusion conformation (MVA-Spf). S protein expressed by MVA-Sdg was found to be expressed and was correctly processed and transported to the cell surface, where it efficiently produced cell–cell fusion. Version Spf, however, was not proteolytically processed, and despite being transported to the plasma membrane, it failed to induce cell–cell fusion. We assessed both vaccine candidates in prime-boost regimens in the susceptible transgenic K18-human angiotensin-converting enzyme 2 (K18-hACE2) in mice and in golden Syrian hamsters. Robust immunity and protection from disease was induced with either vaccine in both animal models. Remarkably, the MVA-Spf vaccine candidate produced higher levels of antibodies, a stronger T cell response, and a higher degree of protection from challenge. In addition, the level of SARS-CoV-2 in the brain of MVA-Spf inoculated mice was decreased to undetectable levels. Those results add to our current experience and range of vaccine vectors and technologies for developing a safe and effective COVID-19 vaccine. Full article

(This article belongs to the Special Issue COVID-19 Vaccine Candidate Development)

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18 pages, 5810 KiB

Open AccessArticle

Immunogenicity and Safety of a Combined Intramuscular/Intranasal Recombinant Spike Protein COVID-19 Vaccine (RCP) in Healthy Adults Aged 18 to 55 Years Old: A Randomized, Double-Blind, Placebo-Controlled, Phase I Trial

by Masoud Solaymani Dodaran, Seyed Reza Banihashemi, Ali Es-haghi, Mohammad Hossein Fallah Mehrabadi, Mojtaba Nofeli, Ali Rezaei Mokarram, Ladan Mokhberalsafa, Fariba Sadeghi, Alireza Ranjbar, Akram Ansarifar, Arash Mohazzab, Seyed Amin Setarehdan, Fahimeh Bagheri Amiri, Vahideh Mohseni, Monireh Hajimoradi, Neda Ghahremanzadeh, Seyed Hossein Razzaz, Safdar Masoomi, Maryam Taghdiri, Mohsen Bagheri, Mohsen Lofti, Akbar Khorasani, Masoud Ghader, Shiva Safari, Masumeh Shahsavn and Saeed Kalantari Show full author list Hide full author list

Vaccines 2023, 11(2), 455; https://doi.org/10.3390/vaccines11020455 - 16 Feb 2023

Cited by 5 | Viewed by 2705

Abstract

Objectives: This study aimed to determine the safety and immunogenicity of a combined intramuscular/intranasal recombinant spike protein COVID-19 vaccine (RCP). Methods: We conducted a randomized, double-blind, placebo-controlled, phase I trial. Three vaccine strengths were compared with an adjuvant-only preparation. It included two intramuscular and a third intranasal dose. Eligible participants were followed for adverse reactions. Specific IgG, secretory IgA, neutralizing antibodies, and cell-mediated immunity were assessed. Results: A total of 153 participants were enrolled (13 sentinels, 120 randomized, 20 non-randomized open-labeled for IgA assessment). No related serious adverse event was observed. The geometric mean ratios (GMRs) and 95% CI for serum neutralizing antibodies compared with placebo two weeks after the second injection were 5.82 (1.46–23.13), 11.12 (2.74–45.09), and 20.70 (5.05–84.76) in 5, 10, and 20 µg vaccine groups, respectively. The GMR for anti-RBD IgA in mucosal fluid two weeks after the intranasal dose was 23.27 (21.27–25.45) in the 10 µg vaccine group. The humoral responses were sustained for up to five months. All vaccine strengths indicated a strong T-helper 1 response. Conclusion: RCP is safe and creates strong and durable humoral and cellular immunity and good mucosal immune response in its 10 µg /200 µL vaccine strengths. Trial registration: IRCT20201214049709N1. Full article

(This article belongs to the Special Issue COVID-19 Vaccine Candidate Development)

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21 pages, 5788 KiB

Open AccessArticle

Toxicological Assessments of a Pandemic COVID-19 Vaccine—Demonstrating the Suitability of a Platform Approach for mRNA Vaccines

by Cynthia M. Rohde, Claudia Lindemann, Michael Giovanelli, Rani S. Sellers, Jan Diekmann, Shambhunath Choudhary, Lila Ramaiah, Annette B. Vogel, Yana Chervona, Alexander Muik and Ugur Sahin

Vaccines 2023, 11(2), 417; https://doi.org/10.3390/vaccines11020417 - 11 Feb 2023

Cited by 6 | Viewed by 4587

Abstract

The emergence of SARS-CoV-2 at the end of 2019 required the swift development of a vaccine to address the pandemic. Nonclinical GLP-compliant studies in Wistar Han rats were initiated to assess the local tolerance, systemic toxicity, and immune response to four mRNA vaccine candidates encoding immunogens derived from the spike (S) glycoprotein of SARS-CoV-2, encapsulated in lipid nanoparticles (LNPs). Vaccine candidates were administered intramuscularly once weekly for three doses at 30 and/or 100 µg followed by a 3-week recovery period. Clinical pathology findings included higher white blood cell counts and acute phase reactant concentrations, lower platelet and reticulocyte counts, and lower RBC parameters. Microscopically, there was increased cellularity (lymphocytes) in the lymph nodes and spleen, increased hematopoiesis in the bone marrow and spleen, acute inflammation and edema at the injection site, and minimal hepatocellular vacuolation. These findings were generally attributed to the anticipated immune and inflammatory responses to the vaccines, except for hepatocyte vacuolation, which was interpreted to reflect hepatocyte LNP lipid uptake, was similar between candidates and resolved or partially recovered at the end of the recovery phase. These studies demonstrated safety and tolerability in rats, supporting SARS-CoV-2 mRNA-LNP vaccine clinical development. Full article

(This article belongs to the Special Issue COVID-19 Vaccine Candidate Development)

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18 pages, 4600 KiB

Open AccessArticle

A Bibliometric Visualization Analysis on Vaccine Development of Coronavirus Disease 2019 (COVID-19)

by Dequan Zeng, Jie Wang, Bin Xiao, Hao Zhang and Xingming Ma

Vaccines 2023, 11(2), 295; https://doi.org/10.3390/vaccines11020295 - 29 Jan 2023

Cited by 2 | Viewed by 1885

Abstract

Coronavirus disease 2019 (COVID-19), beginning in December 2019, has spread worldwide, leading to the death of millions. Owing to the absence of definitive treatment, vaccination against COVID-19 emerged as an effective strategy against the spread of the pandemic. Acceptance of the COVID-19 vaccine has advanced considerably, and vaccine-related research has significantly increased over the past three years. This study aimed to evaluate the content and external characteristics of COVID-19 vaccine-related literature for tracking research trends related to the global COVID-19 vaccine with the means of bibliometrics and visualization maps. A total of 18,285 records in 3499 journals were retrieved in the Web of Science Core Collection database and included in the final analysis. China was the first to focus on COVID-19 vaccine research, while European and American countries started late but developed rapidly. The USA and the UK are the top contributors to COVID-19 vaccine development, with the largest number of publications. The University of Washington and Harvard Medical School were the leading institutions, while Krammer, F. from Icahn School of Medicine at Mount Sinai was the author most active and influential to the topic. The New England Journal of Medicine had the highest number of citations and the highest TLS, and was the most cited and influential journal in the field of COVID-19 vaccine research. COVID-19 vaccine research topics and hotspots focused on populations’ attitudes towards vaccination, immunity-related information analysis of spike proteins, the effectiveness and side effects of the COVID-19 vaccine, and the public management of epidemic transmission. The findings of this study provide the global status, research hotspots and potential trends in the field of COVID-19 vaccine research, which will assist researchers in mastering the knowledge structure, and evaluating and guiding future developmental directions of COVID-19 vaccine Full article

(This article belongs to the Special Issue COVID-19 Vaccine Candidate Development)

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22 pages, 3199 KiB

Open AccessArticle

Immunogenicity and Efficacy of Monovalent and Bivalent Formulations of a Virus-Like Particle Vaccine against SARS-CoV-2

by Matthew D. Resch, Ke Wen, Ryan Mazboudi, Hannah Mulhall Maasz, Mirjana Persaud, Kaitlyn Garvey, Leslie Gallardo, Paul Gottlieb, Aleksandra Alimova, Reza Khayat, Jorge Morales, Helle Bielefeldt-Ohmann, Richard A. Bowen and Jose M. Galarza

Vaccines 2022, 10(12), 1997; https://doi.org/10.3390/vaccines10121997 - 24 Nov 2022

Cited by 5 | Viewed by 2244

Abstract

Virus-like particles (VLPs) offer great potential as a safe and effective vaccine platform against SARS-CoV-2, the causative agent of COVID-19. Here, we show that SARS-CoV-2 VLPs can be generated by expression of the four viral structural proteins in a mammalian expression system. Immunization of mice with a monovalent VLP vaccine elicited a potent humoral response, showing neutralizing activity against multiple variants of SARS-CoV-2. Subsequent immunogenicity and efficacy studies were performed in the Golden Syrian hamster model, which closely resembles the pathology and progression of COVID-19 in humans. Hamsters immunized with a bivalent VLP vaccine were significantly protected from infection with the Beta or Delta variant of SARS-CoV-2. Vaccinated hamsters showed reduced viral load, shedding, replication, and pathology in the respiratory tract. Immunized hamsters also showed variable levels of cross-neutralizing activity against the Omicron variant. Overall, the VLP vaccine elicited robust protective efficacy against SARS-CoV-2. These promising results warrant further study of multivalent VLP vaccines in Phase I clinical trials in humans. Full article

(This article belongs to the Special Issue COVID-19 Vaccine Candidate Development)

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12 pages, 1456 KiB

Open AccessArticle

Heterologous Systemic Prime–Intranasal Boosting Using a Spore SARS-CoV-2 Vaccine Confers Mucosal Immunity and Cross-Reactive Antibodies in Mice as well as Protection in Hamsters

by Paidamoyo M. Katsande, Leira Fernández-Bastit, William T. Ferreira, Júlia Vergara-Alert, Mateusz Hess, Katie Lloyd-Jones, Huynh A. Hong, Joaquim Segales and Simon M. Cutting

Vaccines 2022, 10(11), 1900; https://doi.org/10.3390/vaccines10111900 - 10 Nov 2022

Cited by 3 | Viewed by 2423

Abstract

Background: Current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are administered systemically and typically result in poor immunogenicity at the mucosa. As a result, vaccination is unable to reduce viral shedding and transmission, ultimately failing to prevent infection. One possible solution is that of boosting a systemic vaccine via the nasal route resulting in mucosal immunity. Here, we have evaluated the potential of bacterial spores as an intranasal boost. Method: Spores engineered to express SARS-CoV-2 antigens were administered as an intranasal boost following a prime with either recombinant Spike protein or the Oxford AZD1222 vaccine. Results: In mice, intranasal boosting following a prime of either Spike or vaccine produced antigen-specific sIgA at the mucosa together with the increased production of Th1 and Th2 cytokines. In a hamster model of infection, the clinical and virological outcomes resulting from a SARS-CoV-2 challenge were ameliorated. Wuhan-specific sIgA were shown to cross-react with Omicron antigens, suggesting that this strategy might offer protection against SARS-CoV-2 variants of concern. Conclusions: Despite being a genetically modified organism, the spore vaccine platform is attractive since it offers biological containment, the rapid and cost-efficient production of vaccines together with heat stability. As such, employed in a heterologous systemic prime–mucosal boost regimen, spore vaccines might have utility for current and future emerging diseases. Full article

(This article belongs to the Special Issue COVID-19 Vaccine Candidate Development)

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Review

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26 pages, 741 KiB

Open AccessReview

SARS-CoV-2: An Analysis of the Vaccine Candidates Tested in Combatting and Eliminating the COVID-19 Virus

by Laila Elmancy, Hala Alkhatib and Anis Daou

Vaccines 2022, 10(12), 2086; https://doi.org/10.3390/vaccines10122086 - 07 Dec 2022

Cited by 2 | Viewed by 2177

Abstract

Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), better known as COVID-19, is a highly contagious virus, transferable via air droplets from close human-human contact. The pandemic has led to over 6.5 million deaths worldwide, making it the largest global health crisis since the influenza pandemic in 1918. SARS-CoV-2 rapidly spread around the world, forcing the World Health Organization (WHO) to deem it a global health pandemic after three months of its initiation. The virus has wreaked havoc on many countries worldwide, overwhelming healthcare systems, hence damaging many economies. Even though research has progressed the understanding of the SARS-CoV-2 virus, the information gathered about the vaccine trials and their findings have been scarcely distributed to the public in a single study. The information available to scientists has therefore given researchers a pathway to building an efficacious vehicle to substantially decrease the spread of the virus. The vaccines formulated had many challenges due to multiple factors such as viral mutations and clinical trial delays. This paper will aim to educate readers on the processes that the vaccine candidates took, and better understand the procedures; additionally, we’ll look at all candidates’ findings that went into clinical trials, assessing, analyzing, and evaluating the 27 vaccine candidates that went into phase III trials and the 13 candidates that went into either phase I/II trials. Full article

(This article belongs to the Special Issue COVID-19 Vaccine Candidate Development)

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13 pages, 1288 KiB

Open AccessReview

Knowledge of SARS-CoV-2 Epitopes and Population HLA Types Is Important in the Design of COVID-19 Vaccines

by Rafidah Lani, Nurul Aqidah Senin, Sazaly AbuBakar and Pouya Hassandarvish

Vaccines 2022, 10(10), 1606; https://doi.org/10.3390/vaccines10101606 - 24 Sep 2022

Cited by 4 | Viewed by 2191

Abstract

The COVID-19 pandemic has caused extensive loss of lives and economic hardship. In response, infectious disease experts and vaccine developers promptly responded by bringing forth candidate vaccines, some of which have been listed in the World Health Organization’s Emergency Use Listing. Notwithstanding the diverse worldwide population genetics, the vaccines thus far developed are generic in nature for use worldwide. Differences in the human leukocyte antigen (HLA) in different populations, variation of the T cell epitopes, and the propensity of SARS-CoV-2 genetic mutations left room for improvement of the vaccines. Here, we discussed the implications of COVID-19 vaccination and SARS-CoV-2 infection by taking into consideration SARS-CoV-2 mutations, T cell epitopes, risk factors, and current platforms of candidate vaccines based on the HLA types that are commonly present in Peninsular Malaysia Chinese, Indian, and Malay populations. The HLA types associated with protection against and susceptibility to severe SARS-CoV-2 infection were identified based on reported case-control and cohort studies. The relevance of including the non-spike SARS-CoV-2 proteins in the future COVID-19 vaccines is also highlighted. This review is meant to trigger researchers to acknowledge the importance of investigating the possible relationships between the HLA haplotype and the SARS-CoV-2 strains circulating in different populations. Full article

(This article belongs to the Special Issue COVID-19 Vaccine Candidate Development)

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20 pages, 1853 KiB

Open AccessReview

Fiction and Facts about BCG Imparting Trained Immunity against COVID-19

by Gurpreet Kaur, Sanpreet Singh, Sidhanta Nanda, Mohammad Adeel Zafar, Jonaid Ahmad Malik, Mohammad Umar Arshi, Taruna Lamba and Javed Naim Agrewala

Vaccines 2022, 10(7), 1006; https://doi.org/10.3390/vaccines10071006 - 23 Jun 2022

Cited by 10 | Viewed by 3289

Abstract

The Bacille Calmette-Guérin or BCG vaccine, the only vaccine available against Mycobacterium tuberculosis can induce a marked Th1 polarization of T-cells, characterized by the antigen-specific secretion of IFN-γ and enhanced antiviral response. A number of studies have supported the concept of protection by non-specific boosting of immunity by BCG and other microbes. BCG is a well-known example of a trained immunity inducer since it imparts ‘non-specific heterologous’ immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the recent pandemic. SARS-CoV-2 continues to inflict an unabated surge in morbidity and mortality around the world. There is an urgent need to devise and develop alternate strategies to bolster host immunity against the coronavirus disease of 2019 (COVID-19) and its continuously emerging variants. Several vaccines have been developed recently against COVID-19, but the data on their protective efficacy remains doubtful. Therefore, urgent strategies are required to enhance system immunity to adequately defend against newly emerging infections. The concept of trained immunity may play a cardinal role in protection against COVID-19. The ability of trained immunity-based vaccines is to promote heterologous immune responses beyond their specific antigens, which may notably help in defending against an emergency situation such as COVID-19 when the protective ability of vaccines is suspicious. A growing body of evidence points towards the beneficial non-specific boosting of immune responses by BCG or other microbes, which may protect against COVID-19. Clinical trials are underway to consider the efficacy of BCG vaccination against SARS-CoV-2 on healthcare workers and the elderly population. In this review, we will discuss the role of BCG in eliciting trained immunity and the possible limitations and challenges in controlling COVID-19 and future pandemics. Full article

(This article belongs to the Special Issue COVID-19 Vaccine Candidate Development)

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