Pandemics-Born Revolution in the Preclinical and Clinical Trials of Microbial Vaccines

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 7386

Special Issue Editors

1. Department of Research, Riga Stradins University, LV-1007 Riga, Latvia
2. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
Interests: chronic viral infections and associated cancer; human immunodeficiency virus type 1; human hepatitis C virus; oxidative stress; T cell response; B cell response; DNA vaccines
Special Issues, Collections and Topics in MDPI journals
1. Division of Virology, National Health Laboratory Service, Bloemfontein 9300, South Africa
2. Division of Virology, Faculty of Health Sciences, University of the Free State, Bloemfontein 9300, South Africa
Interests: virology; immunology; viral haemorrhagic fevers and arboviruses
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, Moscow 108819, Russia
Interests: vaccinology; virology; immunology; laboratory animal models for human infections and cancer; non-human primates; SARS-CoV-2; hepatitis E virus

Special Issue Information

Dear Colleagues,

Until December 2019, we were living in the world of successfully functioning vaccines and vaccination programs. New vaccines based on the “naked” nucleic acids, RNA as well as DNA, recognized as promising more than 20 years ago, were not implemented due to our conservatism and cautiousness. The conservative approach to vaccine development was forcibly ended by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that urgently required the recruitment of  all available vaccine platforms, both classic and new ones. 

Among the important challenges in the clinical trials of COVID-19 vaccines was the race against an increasing proportion of people who had previously had an asymptomatic infection, which complicated the recruitment of study participants and the assessment of the results of the trials. Multiple emergences of new virus variants demanded (and still demand) repeated trials of protectivity. The application of vaccines based on mRNA relied on the establishment of complicated worldwide distribution lines. Despite the difficulties, a multitude of “old-fashioned” and novel vaccine types effectively protecting against COVID-19 morbidity and mortality was established. The unprecedented speed of the roll out of these vaccines has shown what can be achieved with global support and commitment, as well as unprecedented funding and institutional support worldwide, which altogether helped to address challenges in the vaccine development process from the lab bench to global distribution. It also highlighted the role of vaccines in the prevention of the disease or reducing disease severity, motivating support to vaccinology as the science that works for people. Our rapid response to the SARS-CoV-2 pandemic was largely possible due to the as-of-yet unused developments in the vaccine research, with their rapid licensing alongside fast development of the large-scale manufacturing technologies. The success in our fight against the pandemic demonstrated the importance of preparedness to new and re-emerging infections, from the development of early vaccine candidates to Phase III clinical trials and massive vaccine production for global use. 

The application of the new vaccine platforms will surely facilitate further rapid development of new (and improved old) vaccines, with respect to both preclinical and clinical trials. This raises the question of whether we should focus our efforts on the broad use of the platforms rolled out for COVID-19, such as mRNA or vectored vaccines, to the new true or perceived pathogen challenges? Enthusiasts suggest that we should apply these platforms to create new-generation vaccines against common infections for which we already have well-functioning vaccines. A more balanced opinion suggests that although the new vaccine platforms have shown remarkable safety and protectivity against COVID-19, reproduction of the success against any other pathogen would take a huge effort, as it did for COVID-19, turning replacement into a highly resource-craving enterprise. 

Among the important difficulties in preclinical COVID-19 vaccine candidate protectivity assessment was the lack of a universal animal model, reproducing all aspects of the infection, including sites of replication and all stages of direct virus-associated and subsequent immune-associated pathogenesis. Because of this, vaccine candidate testing required costly simultaneous use of several laboratory animal models, each having its advantages and drawbacks. Once again, this demonstrated the need to develop reliable (sometimes multiple) animal models for any given pathogen for in vivo trials of both safety and efficacy. Furthermore, the pandemic encouraged health care specialists, research society, and even the general public to realize that the efficacy of antimicrobial drugs and vaccines, as well as their safety, cannot be reliably tested in vitro, despite our efforts to follow the 3R principles of animal research (Replace, Reduce, Refine). 

At the same time, even the best animal models do not guarantee success in human application. Lengthy and laborious clinical trials are needed to prove vaccine safety and demonstrate its efficacy. Pandemics raise the question of whether it is legitimate to truncate/shorten standard clinical trials, assessing safety and efficacy in the case of an emergency.  Moreover, is it acceptable to test the efficacy of vaccines via human pathogen–challenge tests. Before the pandemic, this was only done for influenza. We do not yet know whether the future will give us more examples.

This Special Issue welcomes submissions of experimental papers, short communications, reviews and activity reports focusing on the above problems. We specifically welcome submissions, which consider the impact of the SARS-CoV-2 pandemic on:

  • Development of plug and play platforms approach;
  • Future vaccine discovery/development harnessing the current momentum for vaccine development to create new vaccine platforms;
  • Novel vaccines/technologies for accommodating emerging SARS-CoV-2 variants;
  • Novel vaccines/technologies against other common and emerging (re-emerging) pathogens;
  • Development of animal models to test vaccine efficacy;
  • Vaccine manufacture and upscale now and in the future; 
  • Formulations that aid the stability of vaccines facilitating distribution to less accessible and low resource countries;
  • All aspects addressing vaccine acceptance and hesitancy. 

A special invitation to submit is addressed to the participants of the international conference “Vaccines and vaccination during and post COVID pandemics” held online from December 7–9, 2022 at Riga Stradins University, Riga, Latvia, sponsored by VACCINES. Information on the event can be viewed at the website of Riga Stradins University https://www.rsu.lv/en/vac-vac-2022.

Dr. Maria G. Isaguliants
Prof. Dr. Felicity Jane Burt
Dr. Ilya Gordeychuk
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

  • DNA vaccines
  • RNA vaccines
  • recombinant viral vaccines
  • vaccination techniques
  • vaccine carriers
  • adjuvants
  • vaccine complications, adverse effects
  • vaccines against acute viral infections
  • vaccines against chronic viral infections
  • vaccines against microbial infections
  • vaccines against parasitic infections
  • cancer vaccines
  • animal models
  • vaccine safety tests

Published Papers (5 papers)

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27 pages, 2727 KiB  
Article
In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4+ T-Cells
Vaccines 2023, 11(11), 1662; https://doi.org/10.3390/vaccines11111662 - 30 Oct 2023
Viewed by 1210
Abstract
At the heart of the DNA/ALVAC/gp120/alum vaccine’s efficacy in the absence of neutralizing antibodies is a delicate balance of pro- and anti-inflammatory immune responses that effectively decreases the risk of SIVmac251 acquisition in macaques. Vaccine efficacy is linked to antibodies recognizing the [...] Read more.
At the heart of the DNA/ALVAC/gp120/alum vaccine’s efficacy in the absence of neutralizing antibodies is a delicate balance of pro- and anti-inflammatory immune responses that effectively decreases the risk of SIVmac251 acquisition in macaques. Vaccine efficacy is linked to antibodies recognizing the V2 helical conformation, DC-10 tolerogenic dendritic cells eliciting the clearance of apoptotic cells via efferocytosis, and CCR5 downregulation on vaccine-induced gut homing CD4+ cells. RAS activation is also linked to vaccine efficacy, which prompted the testing of IGF-1, a potent inducer of RAS activation with vaccination. We found that IGF-1 changed the hierarchy of V1/V2 epitope recognition and decreased both ADCC specific for helical V2 and efferocytosis. Remarkably, IGF-1 also reduced the expression of CCR5 on vaccine-induced CD4+ gut-homing T-cells, compensating for its negative effect on ADCC and efferocytosis and resulting in equivalent vaccine efficacy (71% with IGF-1 and 69% without). Full article
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14 pages, 5196 KiB  
Article
Development and Optimal Immune Strategy of an Alum-Stabilized Pickering emulsion for Cancer Vaccines
Vaccines 2023, 11(7), 1169; https://doi.org/10.3390/vaccines11071169 - 28 Jun 2023
Viewed by 1060
Abstract
Therapeutic cancer vaccines are considered as one of the most cost-effective ways to eliminate cancer cells. Although many efforts have been invested into improving their therapeutic effect, transient maturation and activations of dendritic cells (DCs) cause weak responses and hamper the subsequent T [...] Read more.
Therapeutic cancer vaccines are considered as one of the most cost-effective ways to eliminate cancer cells. Although many efforts have been invested into improving their therapeutic effect, transient maturation and activations of dendritic cells (DCs) cause weak responses and hamper the subsequent T cell responses. Here, we report on an alum-stabilized Pickering emulsion (APE) that can load a high number of antigens and continue to release them for extensive maturation and activations of antigen-presenting cells (APCs). After two vaccinations, APE/OVA induced both IFN-γ-secreting T cells (Th1) and IL-4-secreting T cells (Th2), generating effector CD8+ T cells against tumor growth. Additionally, although they boosted the cellular immune responses in the spleen, we found that multiple administrations of cancer vaccines (three or four times in 3-day intervals) may increase the immunosuppression with more PD-1+ CD8+ and LAG-3+ CD8+ T cells within the tumor environment, leading to the diminished overall anti-tumor efficacy. Combining this with anti-PD-1 antibodies evidently hindered the suppressive effect of multiple vaccine administrations, leading to the amplified tumor regression in B16-OVA-bearing mice. Full article
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11 pages, 276 KiB  
Article
DNA Vaccines for Epidemic Preparedness: SARS-CoV-2 and Beyond
Vaccines 2023, 11(6), 1016; https://doi.org/10.3390/vaccines11061016 - 23 May 2023
Cited by 3 | Viewed by 2026
Abstract
We highlight the significant progress in developing DNA vaccines during the SARS-CoV-2 pandemic. Specifically, we provide a comprehensive review of the DNA vaccines that have progressed to Phase 2 testing or beyond, including those that have received authorization for use. DNA vaccines have [...] Read more.
We highlight the significant progress in developing DNA vaccines during the SARS-CoV-2 pandemic. Specifically, we provide a comprehensive review of the DNA vaccines that have progressed to Phase 2 testing or beyond, including those that have received authorization for use. DNA vaccines have significant advantages with regard to the rapidity of production, thermostability, safety profile, and cellular immune responses. Based on user needs and cost, we compare the three devices used in the SARS-CoV-2 clinical trials. Of the three devices, the GeneDerm suction device offers numerous benefits, particularly for international vaccination campaigns. As such, DNA vaccines represent a promising option for future pandemics. Full article
13 pages, 900 KiB  
Article
Long-Term Immunological Memory of SARS-CoV-2 Is Present in Patients with Primary Antibody Deficiencies for up to a Year after Vaccination
Vaccines 2023, 11(2), 354; https://doi.org/10.3390/vaccines11020354 - 03 Feb 2023
Cited by 2 | Viewed by 1562
Abstract
Some studies have found increased coronavirus disease-19 (COVID-19)-related morbidity and mortality in patients with primary antibody deficiencies. Immunization against COVID-19 may, therefore, be particularly important in these patients. However, the durability of the immune response remains unclear in such patients. In this study, [...] Read more.
Some studies have found increased coronavirus disease-19 (COVID-19)-related morbidity and mortality in patients with primary antibody deficiencies. Immunization against COVID-19 may, therefore, be particularly important in these patients. However, the durability of the immune response remains unclear in such patients. In this study, we evaluated the cellular and humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in a cross-sectional study of 32 patients with primary antibody deficiency (n = 17 with common variable immunodeficiency (CVID) and n = 15 with selective IgA deficiency) and 15 healthy controls. Serological and cellular responses were determined using enzyme-linked immunosorbent assay and interferon-gamma release assays. The subsets of B and T lymphocytes were measured using flow cytometry. Of the 32 patients, 28 had completed the vaccination regimen with a median time after vaccination of 173 days (IQR = 142): 27 patients showed a positive spike-peptide-specific antibody response, and 26 patients showed a positive spike-peptide-specific T-cell response. The median level of antibody response in CVID patients (5.47 ratio (IQR = 4.08)) was lower compared to healthy controls (9.43 ratio (IQR = 2.13)). No difference in anti-spike T-cell response was found between the groups. The results of this study indicate that markers of the sustained SARS-CoV-2 spike-specific immune response are detectable several months after vaccination in patients with primary antibody deficiencies comparable to controls. Full article
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21 pages, 334 KiB  
Conference Report
Proceedings of the Online Conference “Vaccines and Vaccination during and Post COVID Pandemics” (7–9 December 2022)
Vaccines 2023, 11(7), 1175; https://doi.org/10.3390/vaccines11071175 - 29 Jun 2023
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Abstract
The COVID-19 pandemic put focus on various aspects of vaccine research and development. These include mass vaccination strategies, vaccination compliance and hesitancy, acceptance of novel vaccine approaches, preclinical and animal models used to assess vaccine safety and efficacy, and many other related issues. [...] Read more.
The COVID-19 pandemic put focus on various aspects of vaccine research and development. These include mass vaccination strategies, vaccination compliance and hesitancy, acceptance of novel vaccine approaches, preclinical and animal models used to assess vaccine safety and efficacy, and many other related issues. These issues were addressed by the international online conference “Vaccines and Vaccination During and Post COVID Pandemics” (VAC&VAC 2022) held on the platform of Riga Stradins University, Riga, Latvia. Conference was supported by the International Society for Vaccines, the National Cancer Institute “Fondazione Pascale” (Naples, Italy), and the scientific journal VACCINES (mdpi). VAC&VAC 2022 attracted nearly 150 participants from 14 countries. This report summarizes conference presentations and their discussion. Sessions covered the topics of (1) COVID-19 vaccine development, evaluation, and attitude towards these vaccines, (2) HPV and cancer vaccines, (3) progress and challenges of HIV vaccine development, (4) new and re-emerging infectious threats, and (5) novel vaccine vehicles, adjuvants, and carriers. Each session was introduced by a plenary lecture from renowned experts from leading research institutions worldwide. The conference also included sessions on research funding and grant writing and an early career researcher contest in which the winners received monetary awards and a chance to publish their results free of charge in the special issue of VACCINES covering the meeting. Full article
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