Vaccines and Vaccine Adjuvants for Infectious Diseases and Autoimmune Diseases

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccine Adjuvants".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 9957

Special Issue Editor

Department of Environmental and Biosciences, School of Business, Innovation and Sustainability (FIH), Halmstad University, Halmstad, Sweden
Interests: infectious diseases; autoimmune diseases; bacterial outer-membrane vesicles; adjuvants; vaccines; polymers; autoantibodies; animal models

Special Issue Information

Dear Colleagues,

Vaccines are essential in eradicating or controlling many infectious diseases. Vaccinations not only prevent these diseases, but also contribute to reducing the rate of sepsis caused by these infections and other related complications. However, infections (bacterial, viral, fungal and parasitic) or exposure to microbial organisms may initiate and/or exacerbate autoimmune diseases. In this context, several possible mechanisms (epitope spreading, bystander activation molecular mimicry, etc.) are postulated. In addition, microbial components are indispensable in several animal models of autoimmune diseases. Recent concerns in this area include the autoimmune manifestations associated with COVID-19 vaccines, although incidences of autoimmune diseases after other vaccinations were reported as well. Even then, epidemiological studies do not support vaccination as a cause for the development of systemic autoimmune diseases. At the same time, people living with autoimmune disease(s) need to take care of themselves to protect against various infections. Therefore, on this topic, we invite original and review articles covering the following three aspects: 

  • Central theme: development of vaccines for infectious diseases or autoimmune diseases.
  • Exploration: how vaccines for infectious diseases might cause autoimmune diseases.
  • Accessories: vaccine adjuvants (natural and synthetic polymers, microbial and nonmicrobial components, their mode of action, and beneficial and adverse effects).

Prof. Dr. Kutty Selva Nandakumar
Guest Editor

Manuscript Submission Information

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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

  • infectious disease
  • autoimmune disease
  • vaccine
  • adjuvant
  • mechanisms

Published Papers (6 papers)

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Editorial

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4 pages, 182 KiB  
Editorial
Vaccines and Vaccine Adjuvants for Infectious Diseases and Autoimmune Diseases
by Kutty Selva Nandakumar
Vaccines 2023, 11(2), 202; https://doi.org/10.3390/vaccines11020202 - 17 Jan 2023
Cited by 1 | Viewed by 1323
Abstract
A dynamic association of specific microbiota during different stages of human life is well documented [...] Full article

Research

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16 pages, 3864 KiB  
Article
A Next-Generation Adenoviral Vaccine Elicits Mucosal and Systemic Immunogenicity and Reduces Viral Shedding after SARS-CoV-2 Challenge in Nonhuman Primates
by Sarah N. Tedjakusuma, Colin A. Lester, Elena D. Neuhaus, Emery G. Dora, Samanta Gutierrez, Molly R. Braun, Sean N. Tucker and Becca A. Flitter
Vaccines 2024, 12(2), 132; https://doi.org/10.3390/vaccines12020132 - 27 Jan 2024
Viewed by 2044
Abstract
As new SARS-CoV-2 variants continue to emerge and impact communities worldwide, next-generation vaccines that enhance protective mucosal immunity may have a significant impact on productive infection and transmission. We have developed recombinant non-replicating adenovirus serotype 5 (rAd5) vaccines delivered by mucosal administration that [...] Read more.
As new SARS-CoV-2 variants continue to emerge and impact communities worldwide, next-generation vaccines that enhance protective mucosal immunity may have a significant impact on productive infection and transmission. We have developed recombinant non-replicating adenovirus serotype 5 (rAd5) vaccines delivered by mucosal administration that express both target antigen and a novel molecular adjuvant within the same cell. Here, we describe the immunogenicity of three unique SARS-CoV-2 rAd5 vaccine candidates and their efficacy following viral challenge in non-human primates (NHPs). Intranasal immunization with rAd5 vaccines expressing Wuhan, or Beta variant spike alone, or Wuhan spike and nucleocapsid elicited strong antigen-specific serum IgG and IgA with neutralizing activity against multiple variants of concern (VOC). Robust cross-reactive mucosal IgA was detected after a single administration of rAd5, which showed strong neutralizing activity against multiple VOC. Additionally, mucosal rAd5 vaccination increased spike-specific IFN-γ producing circulating T-cells. Upon Beta variant SARS-CoV-2 challenge, all the vaccinated NHPs exhibited significant reductions in viral load and infectious particle shedding in both the nasal passages and lower airways. These findings demonstrate that mucosal rAd5 immunization is highly immunogenic, confers protective cross-reactive antibody responses in the circulation and mucosa, and reduces viral load and shedding after SARS-CoV-2 challenge. Full article
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25 pages, 12275 KiB  
Article
Leptospira Lipid A Is a Potent Adjuvant That Induces Sterilizing Immunity against Leptospirosis
by Vivek P. Varma, Mohammad Kadivella, Sridhar Kavela and Syed M. Faisal
Vaccines 2023, 11(12), 1824; https://doi.org/10.3390/vaccines11121824 - 06 Dec 2023
Viewed by 1117
Abstract
Leptospirosis is a globally significant zoonotic disease. The current inactivated vaccine offers protection against specific serovars but does not provide complete immunity. Various surface antigens, such as Leptospira immunoglobulin-like proteins (LigA and LigB), have been identified as potential subunit vaccine candidates. However, these [...] Read more.
Leptospirosis is a globally significant zoonotic disease. The current inactivated vaccine offers protection against specific serovars but does not provide complete immunity. Various surface antigens, such as Leptospira immunoglobulin-like proteins (LigA and LigB), have been identified as potential subunit vaccine candidates. However, these antigens require potent adjuvants for effectiveness. Bacterial lipopolysaccharides (LPSs), including lipid A, are a well-known immunostimulant, and clinical adjuvants often contain monophosphoryl lipid A (MPLA). Being less endotoxic, we investigated the adjuvant properties of lipid A isolated from L. interrogans serovar Pomona (PLA) in activating innate immunity and enhancing antigen-specific adaptive immune responses. PLA activated macrophages to a similar degree as MPLA, albeit at a higher dose, suggesting that it is less potent in stimulation than MPLA. Mice immunized with a variable portion of LigA (LAV) combined with alum and PLA (LAV-alum-PLA) exhibited significantly higher levels of LAV-specific humoral and cellular immune responses compared to alum alone but similar to those induced by alum-MPLA. The adjuvant activity of PLA resembles that of MPLA and is primarily achieved through the increased recruitment, activation, and uptake of antigens by innate immune cells. Furthermore, like MPLA, PLA formulation establishes a long-lasting memory response. Notably, PLA demonstrated superior potency than MPLA formulation and provided sterilizing immunity against the leptospirosis in a hamster model. Overall, our study sheds light on the adjuvant properties of Leptospira lipid A and offers promising avenues for developing LPS-based vaccines against this devastating zoonotic disease. Full article
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11 pages, 1906 KiB  
Article
CpG 1018 Is an Effective Adjuvant for Influenza Nucleoprotein
by Yibo Li and Xinyuan Chen
Vaccines 2023, 11(3), 649; https://doi.org/10.3390/vaccines11030649 - 14 Mar 2023
Cited by 1 | Viewed by 2174
Abstract
Current influenza vaccines mainly induce neutralizing antibodies against the highly variable surface antigen hemagglutinin and require annual manufacturing and immunization. Different from surface antigens, intracellular nucleoprotein (NP) is highly conserved and has been an attractive target to develop universal T cell vaccines against [...] Read more.
Current influenza vaccines mainly induce neutralizing antibodies against the highly variable surface antigen hemagglutinin and require annual manufacturing and immunization. Different from surface antigens, intracellular nucleoprotein (NP) is highly conserved and has been an attractive target to develop universal T cell vaccines against influenza. Yet, influenza NP protein mainly induces humoral immune responses and lacks the ability to induce potent cytotoxic T lymphocyte (CTL) responses, key for the success of universal T cell vaccines. This study compared CpG 1018 and AddaVax to enhance recombinant NP-induced CTL responses and protection in murine models. CpG 1018 was explored to boost intradermal NP immunization, while AddaVax was explored to boost intramuscular NP immunization due to the high risk of AddaVax adjuvant to induce significant local reactions following intradermal delivery. We found CpG 1018 was highly effective to enhance NP-induced humoral and cellular immune responses superior to AddaVax adjuvant. Furthermore, CpG 1018 potentiated Th1-biased antibody responses, while AddaVax enhanced Th1/Th2-balanced antibody responses. CpG 1018 significantly enhanced IFNγ-secreting Th1 cells, while AddaVax adjuvant significantly increased IL4-secreting Th2 cells. Influenza NP immunization in the presence of CpG 1018 induced significant protection against lethal viral challenges, while influenza NP immunization in the presence of AddaVax failed to elicit significant protection. Our data validated CpG 1018 as an effective adjuvant to enhance influenza NP-induced CTL responses and protection. Full article
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11 pages, 4238 KiB  
Article
Overcoming Aging-Associated Poor Influenza Vaccine Responses with CpG 1018 Adjuvant
by Xinliang Kang, Yibo Li, Yiwen Zhao and Xinyuan Chen
Vaccines 2022, 10(11), 1894; https://doi.org/10.3390/vaccines10111894 - 10 Nov 2022
Cited by 2 | Viewed by 1589
Abstract
Aging is associated with diminished immune system function, which renders old people vulnerable to influenza infection and also less responsive to influenza vaccination. This study explored whether the CpG 1018 adjuvant was effective in enhancing influenza vaccine efficacy in aged mice equivalent to [...] Read more.
Aging is associated with diminished immune system function, which renders old people vulnerable to influenza infection and also less responsive to influenza vaccination. This study explored whether the CpG 1018 adjuvant was effective in enhancing influenza vaccine efficacy in aged mice equivalent to human beings in their late 50s to early 60s. Using the influenza pandemic 2009 H1N1 (pdm09) vaccine as a model, we found that the CpG 1018 adjuvant could significantly enhance the pdm09 vaccine-induced serum antibody titer, while the pdm09 vaccine alone failed to elicit significant antibody titer. In contrast, the pdm09 vaccine alone elicited significant antibody titer in young adult mice. Antibody subtype analysis found that the pdm09 vaccine alone elicited Th2-biased antibody responses in young adult mice, while incorporation of the CpG 1018 adjuvant promoted the elicitation of potent Th1-biased antibody responses in aged mice. The pdm09 vaccine alone was further found to induce significant expansion of Th2 cells in young adult mice, while incorporation of the CpG 1018 adjuvant stimulated significant expansion of Th1 cells in aged mice. The CpG 1018 adjuvant also stimulated vaccine-specific cytotoxic T lymphocytes in aged mice. The pdm09 vaccine in the presence of CpG 1018 elicited significant protection against lethal viral challenges, while the pdm09 vaccine alone failed to confer significant protection in young adult or aged mice. Our study provided strong evidence to support the high effectiveness of the CpG 1018 adjuvant to boost influenza vaccination in aged mouse models. Full article
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Review

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11 pages, 2223 KiB  
Review
Polymer Chemistry Defines Adjuvant Properties and Determines the Immune Response against the Antigen or Vaccine
by Akhilesh Kumar Shakya and Kutty Selva Nandakumar
Vaccines 2023, 11(9), 1395; https://doi.org/10.3390/vaccines11091395 - 22 Aug 2023
Viewed by 1112
Abstract
Activation of the immune system is a needed for designing new antigen/drug delivery systems to develop new therapeutics and for developing animal disease models to study the disease pathogenesis. A weak antigen alone is insufficient to activate the immune system. Sometimes, assistance in [...] Read more.
Activation of the immune system is a needed for designing new antigen/drug delivery systems to develop new therapeutics and for developing animal disease models to study the disease pathogenesis. A weak antigen alone is insufficient to activate the immune system. Sometimes, assistance in the form of polymers is needed to control the release of antigens under in vivo conditions or in the form of an adjuvant to activate the immune system efficiently. Many kinds of polymers from different functional groups are suitable as microbial antigens for inducing therapeutic immune responses against infectious diseases at the preclinical level. The choice of the functionality of polymer varies as per the application type. Polymers from the acid and ester groups are the most common types investigated for protein-based antigens. However, electrostatic interaction-displaying polymers like cationic polymers are the most common type for nucleic acid-based antigens. Metal coordination chemistry is commonly used in polymers designed for cancer immunotherapeutic applications to suppress inflammation and induce a protective immune response. Amide chemistry is widely deployed in polymers used to develop antigen-specific disease models like the experimental autoimmune arthritis murine model. Full article
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