New Trends in Vaccine Characterization, Formulations, and Development

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

Deadline for manuscript submissions: closed (20 February 2024) | Viewed by 22898

Special Issue Editor


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Guest Editor
Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
Interests: yeast-based vaccines; yeast-based screening of chemicals
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Vaccines represent the most reliable and safe means in the fight against infectious diseases. Over the last few decades, several platforms have been used for vaccine development, formulation, and delivery. Each platform its own unique advantages over other platforms. This has led to the availability of different types of vaccines ranging from conventional attenuated or killed whole pathogen to subunit vaccines and, recently, nucleic acid-based vaccines such as mRNA-based vaccines. Even though modern vaccines are proven to be safe and effective, they still suffer from numerous limitations such as poor thermostability, short shelf life at room temperature, and the requirement for specialized needles and syringes. To overcome these issues, new formulations and modes of vaccine delivery are currently under investigation.

Further global application of mRNA-based COVID-19 vaccines have demonstrated the applicability and safety of these vaccines. This will likely open the possibility of treating infectious diseases that have proven difficult to target using conventional vaccine development regimes. Whether the available mRNA-based technology is effective against other infectious diseases remains unknown. More research in this direction is needed, which requires larger and more significant efforts in this direction. Thus, we would like to encourage submissions to this Special Issue on recent advances made in vaccine characterization, formulation, and development, for which original research articles, reviews, communications, case reports, and clinical trials mentioning technological improvements in the field of vaccines are welcome. Papers describing novel formulations, the development of new platforms for vaccine delivery, identification of novel adjuvants, and novel modes of delivery are also welcome.

I look forward to receiving your contributions.

Dr. Ravinder Kumar
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

  • vaccines
  • formulation
  • development
  • vaccine delivery
  • mRNA vaccines
  • DNA vaccines
  • subunit vaccine
  • adjuvant
  • yeast-based vaccines
  • virus-like particles (VLPs)
  • surface display
  • production process
  • quality control

Published Papers (10 papers)

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Editorial

Jump to: Research, Review

3 pages, 173 KiB  
Editorial
New Trends in Vaccine Characterization, Formulations, and Development
by Ravinder Kumar
Vaccines 2024, 12(3), 338; https://doi.org/10.3390/vaccines12030338 - 20 Mar 2024
Viewed by 738
Abstract
More than eight decades have passed since the development of the first vaccine in the 1940s [...] Full article
(This article belongs to the Special Issue New Trends in Vaccine Characterization, Formulations, and Development)

Research

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10 pages, 1004 KiB  
Article
Immunological Response to Subcutaneous and Intranasal Administration of SARS-CoV-2 Spike Protein in Mice
by Mao Kinoshita, Kentaro Muranishi, Ken Kawaguchi, Kazuki Sudo, Keita Inoue, Hiroyasu Ishikura and Teiji Sawa
Vaccines 2024, 12(4), 343; https://doi.org/10.3390/vaccines12040343 - 22 Mar 2024
Viewed by 772
Abstract
In novel coronavirus infection (COVID-19), the outbreak of acute lung injury due to trans-airway infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the starting point of severe disease. The COVID-19 pandemic highlights the need for a vaccine that prevents not [...] Read more.
In novel coronavirus infection (COVID-19), the outbreak of acute lung injury due to trans-airway infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the starting point of severe disease. The COVID-19 pandemic highlights the need for a vaccine that prevents not only the disease but also its infection. Currently, the SARS-CoV-2 vaccine is administered via intramuscular injection and is generally not immunogenic to the mucosa. As a result, current vaccinations fail to reduce viral shedding and transmission and ultimately do not prevent infection. We established a mouse vaccine model in which a single dose of S1 protein and aluminum oxide gel (alum) subcutaneous vaccine was followed by a booster dose of S1 protein and CpG oligodeoxynucleotide intranasal vaccine. The group that received two doses of the intranasal vaccine booster showed a significant increase in IgG and IgA antibody titers against S1 and RBD in serum and BAL, and a significant difference in neutralizing antibody titers, particularly in BAL. One intranasal vaccine booster did not induce sufficient immunity, and the vaccine strategy with two booster intranasal doses produced systemic neutralizing antibodies and mucus-neutralizing antibodies against SARS-CoV-2. It will be an important tool against the emergence of new viruses and the next pandemic. Full article
(This article belongs to the Special Issue New Trends in Vaccine Characterization, Formulations, and Development)
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19 pages, 1852 KiB  
Article
Evaluation of a Combined Live Attenuated Vaccine against Lumpy Skin Disease, Contagious Bovine Pleuropneumonia and Rift Valley Fever
by Zohra Bamouh, Amal Elarkam, Soufiane Elmejdoub, Jihane Hamdi, Zineb Boumart, Greg Smith, Matthew Suderman, Mahder Teffera, Hezron Wesonga, Stephen Wilson, Douglas M. Watts, Shawn Babiuk, Brad Pickering and Mehdi Elharrak
Vaccines 2024, 12(3), 302; https://doi.org/10.3390/vaccines12030302 - 13 Mar 2024
Viewed by 893
Abstract
The use of effective vaccines is among the most important strategies for the prevention and progressive control of transboundary infectious animal diseases. However, the use of vaccine is often impeded by the cost, a lack of cold chains and other factors. In resource-limited [...] Read more.
The use of effective vaccines is among the most important strategies for the prevention and progressive control of transboundary infectious animal diseases. However, the use of vaccine is often impeded by the cost, a lack of cold chains and other factors. In resource-limited countries in Africa, one approach to improve coverage and reduce cost is to vaccinate against multiple diseases using combined vaccines. Therefore, the objective of this study was to evaluate a combined vaccine for the prevention and control of Lumpy Skin Disease (LSD), Contagious Bovine Pleuropneumonia (CBPP) and Rift Valley fever (RVF). The LSD and CBPP were formulated as a combined vaccine, and the RVF was formulated separately as live attenuated vaccines. These consisted of a Mycoplasma MmmSC T1/44 strain that was propagated in Hayflick-modified medium, RVF virus vaccine, C13T strain prepared in African green monkey cells (Vero), and the LSDV Neethling vaccine strain prepared in primary testis cells. The vaccines were tested for safety via the subcutaneous route in both young calves and pregnant heifers with no side effect, abortion or teratogenicity. The vaccination of calves induced seroconversions for all three vaccines starting from day 7 post-vaccination (PV), with rates of 50% for LSD, 70% for CBPP and 100% for RVF, or rates similar to those obtained with monovalent vaccines. The challenge of cattle vaccinated with the LSD/CBPP and the RVF vaccine afforded full protection against virulent strains of LSDV and RVFV. A satisfactory level of protection against a CBPP challenge was observed, with 50% of protection at 6 months and 81% at 13 months PV. A mass vaccination trial was performed in four regions of Burkina Faso that confirmed safety and specific antibody responses induced by the vaccines. The multivalent LSD/CBPP+RVF vaccine provides a novel and beneficial approach to the control of the three diseases through one intervention and, therefore, reduces the cost and improves vaccination coverage. Full article
(This article belongs to the Special Issue New Trends in Vaccine Characterization, Formulations, and Development)
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14 pages, 1522 KiB  
Article
Trends in COVID-19 Vaccine Development: Vaccine Platform, Developer, and Nationality
by Ryo Okuyama
Vaccines 2024, 12(3), 259; https://doi.org/10.3390/vaccines12030259 - 01 Mar 2024
Viewed by 1250
Abstract
Various vaccine platforms, including emerging platforms, have been applied in the development of COVID-19 vaccines. Biotechnology startups often lead the development of new medical technologies, whereas major pharmaceutical companies and public institutions have long contributed to vaccine development. In this study, vaccine platforms [...] Read more.
Various vaccine platforms, including emerging platforms, have been applied in the development of COVID-19 vaccines. Biotechnology startups often lead the development of new medical technologies, whereas major pharmaceutical companies and public institutions have long contributed to vaccine development. In this study, vaccine platforms and developers involved in COVID-19 vaccine development were analyzed, elucidating the trends of vaccine platforms used, the country distribution of the developers, and differences in the profiles of developers by vaccine platform technologies and country. The analysis revealed that conventional, established, and emerging vaccine platforms have been widely used and that older platforms are more advanced in clinical development. It also demonstrated the emergence of China, in addition to the U.S., while many pharmerging countries have been engaged in development. Startups have significantly contributed to the development of viral vector and RNA-based vaccines, suggesting their important role in the application of novel technologies. The major developers differ by country and region. Alliances, including international collaborations, have progressed in late clinical development. Based on these results, future perspectives of pandemic vaccine development and implications for policy and corporate strategies are discussed. Full article
(This article belongs to the Special Issue New Trends in Vaccine Characterization, Formulations, and Development)
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14 pages, 2245 KiB  
Article
Candida parapsilosis Cell Wall Proteome Characterization and Effectiveness against Hematogenously Disseminated Candidiasis in a Murine Model
by Xiaolong Gong, Vartika Srivastava, Previn Naicker, Amber Khan and Aijaz Ahmad
Vaccines 2023, 11(3), 674; https://doi.org/10.3390/vaccines11030674 - 16 Mar 2023
Cited by 1 | Viewed by 1720
Abstract
Candida parapsilosis poses huge treatment challenges in the clinical settings of South Africa, and often causes infections among immunocompromised patients and underweight neonates. Cell wall proteins have been known to play vital roles in fungal pathogenesis, as these are the first points of [...] Read more.
Candida parapsilosis poses huge treatment challenges in the clinical settings of South Africa, and often causes infections among immunocompromised patients and underweight neonates. Cell wall proteins have been known to play vital roles in fungal pathogenesis, as these are the first points of contact toward environments, the host, and the immune system. This study characterized the cell wall immunodominant proteins of pathogenic yeast C. parapsilosis and evaluated their protective effects in mice, which could add value in vaccine development against the rising C. parapsilosis infections. Among different clinical strains, the most pathogenic and multidrug-resistant C. parapsilosis isolate was selected based on their susceptibility towards antifungal drugs, proteinase, and phospholipase secretions. Cell wall antigens were prepared by β-mercaptoethanol/ammonium bicarbonate extraction from selected C. parapsilosis strains. Antigenic proteins were identified using LC–MS/MS, where 933 proteins were found, with 34 being immunodominant. The protective effect of the cell wall immunodominant proteins was observed by immunizing BALB/c mice with cell wall protein extracts. After the immunization and booster, the BALC/c mice were challenged with a lethal dose of C. parapsilosis. In vivo results demonstrated increased survival rates and lower fungal burden in vital organs in the immunized mice compared to the unimmunized mice, thereby confirming the immunogenic property of cell wall-associated proteins of C. parapsilosis. Therefore, these results advocated the potential of these cell wall proteins to act as biomarkers for the development of diagnostic assays and/or vaccines against infections caused by C. parapsilosis. Full article
(This article belongs to the Special Issue New Trends in Vaccine Characterization, Formulations, and Development)
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19 pages, 2641 KiB  
Article
Vaccinating Children against SARS-CoV-2: A Literature Review and Survey of International Experts to Assess Safety, Efficacy and Perceptions of Vaccine Use in Children
by Lauren Hookham, Hillary C. Lee, Divya A. Patel, Mariana Coelho, Norberto Giglio, Kirsty Le Doare and Pia S. Pannaraj
Vaccines 2023, 11(1), 78; https://doi.org/10.3390/vaccines11010078 - 29 Dec 2022
Cited by 4 | Viewed by 1730
Abstract
Introduction: The balance of risks and benefits of COVID-19 vaccination in children is more complex than in adults with limited paediatric data resulting in no global consensus on whether all healthy children should be vaccinated. We sought to assess the safety, efficacy, and [...] Read more.
Introduction: The balance of risks and benefits of COVID-19 vaccination in children is more complex than in adults with limited paediatric data resulting in no global consensus on whether all healthy children should be vaccinated. We sought to assess the safety, efficacy, and effectiveness of childhood vaccination against SARS-CoV-2, as well as better understanding perceptions of vaccination in parents and vaccine experts. Methods: We performed a literature review for COVID-19 vaccine safety, efficacy, effectiveness, and perceptions. We searched international safety databases for safety data and developed an electronic survey to elicit country-specific COVID-19 immunisation data, including vaccine regulations, policies, rates, and public attitudes solicited from vaccine experts. Results: Nine studies were included in the final safety analysis. Local reactions were frequently reported across all studies and vaccine types. Adverse events reported to surveillance systems tended to be non-serious, and commonly included injection site reactions and dizziness. Twenty-three studies reported immunogenicity, efficacy, and effectiveness data. There were nine randomised control trials of six different vaccine types, which showed seroconversion of neutralising antibodies in vaccinated children ranging from 88% to 100%. The vaccine efficacy for Pfizer and Moderna vaccines ranged from 88% to 100%. There were 118 survey responses representing 55 different countries. Reported vaccination rates ranged from <1% to 98%. Most respondents described “mixed opinions” regarding paediatric vaccination policies in their country. By region, a more positive public attitude towards vaccination correlated with higher vaccination rates. Discussion: In this mixed-methods review, we have found evidence that vaccination against COVID-19 in children is safe, efficacious, and effective. Overall, the combined evidence from both the literature review and survey highlights the need for further data on both the safety and effectiveness of COVID-19 vaccinations in children. Full article
(This article belongs to the Special Issue New Trends in Vaccine Characterization, Formulations, and Development)
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Review

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37 pages, 1601 KiB  
Review
Vaccine Strategies to Elicit Mucosal Immunity
by Yufeng Song, Frances Mehl and Steven L. Zeichner
Vaccines 2024, 12(2), 191; https://doi.org/10.3390/vaccines12020191 - 13 Feb 2024
Viewed by 1796
Abstract
Vaccines are essential tools to prevent infection and control transmission of infectious diseases that threaten public health. Most infectious agents enter their hosts across mucosal surfaces, which make up key first lines of host defense against pathogens. Mucosal immune responses play critical roles [...] Read more.
Vaccines are essential tools to prevent infection and control transmission of infectious diseases that threaten public health. Most infectious agents enter their hosts across mucosal surfaces, which make up key first lines of host defense against pathogens. Mucosal immune responses play critical roles in host immune defense to provide durable and better recall responses. Substantial attention has been focused on developing effective mucosal vaccines to elicit robust localized and systemic immune responses by administration via mucosal routes. Mucosal vaccines that elicit effective immune responses yield protection superior to parenterally delivered vaccines. Beyond their valuable immunogenicity, mucosal vaccines can be less expensive and easier to administer without a need for injection materials and more highly trained personnel. However, developing effective mucosal vaccines faces many challenges, and much effort has been directed at their development. In this article, we review the history of mucosal vaccine development and present an overview of mucosal compartment biology and the roles that mucosal immunity plays in defending against infection, knowledge that has helped inform mucosal vaccine development. We explore new progress in mucosal vaccine design and optimization and novel approaches created to improve the efficacy and safety of mucosal vaccines. Full article
(This article belongs to the Special Issue New Trends in Vaccine Characterization, Formulations, and Development)
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11 pages, 574 KiB  
Review
A Perspective on Oral Immunotherapeutic Tools and Strategies for Autoimmune Disorders
by Akhilesh Kumar Shakya, Buddhadev Mallick and Kutty Selva Nandakumar
Vaccines 2023, 11(6), 1031; https://doi.org/10.3390/vaccines11061031 - 27 May 2023
Cited by 1 | Viewed by 1775
Abstract
Oral immune tolerance is a physiological process to achieve tolerance against autoimmunity by oral ingestion of self-antigen(s) or other therapeutics. At the cellular level, oral tolerance suppresses autoimmune diseases by activating FoxP-positive and -negative regulatory T cells (Tregs) and/or causing clonal anergy or [...] Read more.
Oral immune tolerance is a physiological process to achieve tolerance against autoimmunity by oral ingestion of self-antigen(s) or other therapeutics. At the cellular level, oral tolerance suppresses autoimmune diseases by activating FoxP-positive and -negative regulatory T cells (Tregs) and/or causing clonal anergy or deletion of autoreactive T cells, affecting B cell tolerance. However, oral delivery of antigens/biologics is challenging due to their instability in the harsh environment of the gastrointestinal (GI) tract. Several antigen/drug delivery tools and approaches, including micro/nanoparticles and transgenic plant-based delivery systems, have been explored to demonstrate oral immune tolerance for different autoimmune diseases successfully. However, despite the effectiveness, variation in results, dose optimization, and undesirable immune system activation are the limitations of the oral approach to further advancement. From this perspective, the current review discusses the oral tolerance phenomenon, cellular mechanisms, antigen delivery tools and strategies, and its challenges. Full article
(This article belongs to the Special Issue New Trends in Vaccine Characterization, Formulations, and Development)
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16 pages, 832 KiB  
Review
The Integrated Consideration of Vaccine Platforms, Adjuvants, and Delivery Routes for Successful Vaccine Development
by Michael Kozak and Jiafen Hu
Vaccines 2023, 11(3), 695; https://doi.org/10.3390/vaccines11030695 - 17 Mar 2023
Cited by 7 | Viewed by 2598
Abstract
Vaccines have proven to be the most cost-efficient and reasonable way to fight and exterminate virulent pathogens. Vaccines can be designed using a variety of platforms including inactivated/attenuated pathogen or subunits of it. The most recent COVID mRNA vaccines have employed nucleic acid [...] Read more.
Vaccines have proven to be the most cost-efficient and reasonable way to fight and exterminate virulent pathogens. Vaccines can be designed using a variety of platforms including inactivated/attenuated pathogen or subunits of it. The most recent COVID mRNA vaccines have employed nucleic acid sequences for the antigen of interest to combat the pandemic. Different vaccine platforms have been chosen for different licensed vaccines which all have shown their ability to induce durable immune responses and protection. In addition to platforms, different adjuvants have been used to strengthen the immunogenicity of vaccines. Among the delivery routes, intramuscular injection has been the most common for vaccination. In this review, we present a historical overview of the integrated consideration of vaccine platforms, adjuvants, and delivery routes in the success of vaccine development. We also discuss the advantages and limitations of each choice in the efficacy of vaccine development. Full article
(This article belongs to the Special Issue New Trends in Vaccine Characterization, Formulations, and Development)
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23 pages, 1551 KiB  
Review
Yeast-Based Virus-like Particles as an Emerging Platform for Vaccine Development and Delivery
by Vartika Srivastava, Kripa N. Nand, Aijaz Ahmad and Ravinder Kumar
Vaccines 2023, 11(2), 479; https://doi.org/10.3390/vaccines11020479 - 18 Feb 2023
Cited by 9 | Viewed by 8208
Abstract
Virus-like particles (VLPs) are empty, nanoscale structures morphologically resembling viruses. Internal cavity, noninfectious, and particulate nature with a high density of repeating epitopes, make them an ideal platform for vaccine development and drug delivery. Commercial use of Gardasil-9 and Cervarix showed the usefulness [...] Read more.
Virus-like particles (VLPs) are empty, nanoscale structures morphologically resembling viruses. Internal cavity, noninfectious, and particulate nature with a high density of repeating epitopes, make them an ideal platform for vaccine development and drug delivery. Commercial use of Gardasil-9 and Cervarix showed the usefulness of VLPs in vaccine formulation. Further, chimeric VLPs allow the raising of an immune response against different immunogens and thereby can help reduce the generation of medical or clinical waste. The economically viable production of VLPs significantly impacts their usage, application, and availability. To this end, several hosts have been used and tested. The present review will discuss VLPs produced using different yeasts as fermentation hosts. We also compile a list of studies highlighting the expression and purification of VLPs using a yeast-based platform. We also discuss the advantages of using yeast to generate VLPs over other available systems. Further, the issues or limitations of yeasts for producing VLPs are also summarized. The review also compiles a list of yeast-derived VLP-based vaccines that are presently in public use or in different phases of clinical trials. Full article
(This article belongs to the Special Issue New Trends in Vaccine Characterization, Formulations, and Development)
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