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A Century of Vaccine Adjuvants: From 1920 to 2020 and...
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A Century of Vaccine Adjuvants: From 1920 to 2020 and Beyond

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

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 8760

Special Issue Editor

Dr. Sjoerd T. Schetters

E-Mail Website
Guest Editor
Department of Molecular Cell Biology and Immunology, Vrije Universiteit Amsterdam, 1081 HZ Amsterdam, The Netherlands
Interests: antitumor vaccines; adjuvants; adaptive immunity; eosinophils; checkpoint blockade; allergy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

In the 20th century, science has come a long way in understanding protective immunity and its practical use in vaccinology. From the efficacy of Jenner’s variolation, through the discovery of inactivated biological sources as vaccine compounds by Louis Pasteur and Calmette and Guerin, to the development of tuberculosis, diphtheria, tetanus, and whooping cough vaccines in 1920-30, practical immunology has proven vital to the ultimate prosperity of humanity. As our understanding of adaptive immunity increases, there is a growing urge to define specific modes of action that result in long-term protective immunity. In principle, vaccines contain antigen and innate immune activators to satisfy the preconditions of adaptive immunity. The delivery of antigens can be highly defined (for example, synthetic peptides or mRNA) or included by association (for example, live/attenuated pathogens). However, not all antigen modalities used in vaccination elicit the innate immune activation needed for downstream adaptive immunity. Instead, these antigens are mixed with or conjugated to immunogenic compounds, called adjuvants, capable of activating dendritic cells. A wide variety of adjuvants have now been described, designed, and used in clinical settings (see figure). With the advent of new vaccines, further pushed to the clinic because of the current COVID-19 pandemic, there is a need to understand the immune stimulatory capacity of adjuvants in vaccine formulations. In this issue of Vaccines, we will explore these concepts further and provide a collection of excellent scientific manuscripts aimed at increasing our understanding of vaccinology.

Dr. Sjoerd T.T. Schetters
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

  • vaccine adjuvants
  • vaccine formulations
  • vaccine development

Published Papers (4 papers)

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Research

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13 pages, 1508 KiB  
Article
Poly(hydrophobic Amino Acids) and Liposomes for Delivery of Vaccine against Group A Streptococcus
by Armira Azuar, Harrison Y. R. Madge, Jennifer C. Boer, Jazmina L. Gonzalez Cruz, Jingwen Wang, Zeinab G. Khalil, Cyril Deceneux, Georgia Goodchild, Jieru Yang, Prashamsa Koirala, Waleed M. Hussein, Robert J. Capon, Magdalena Plebanski, Istvan Toth and Mariusz Skwarczynski
Vaccines 2022, 10(8), 1212; https://doi.org/10.3390/vaccines10081212 - 29 Jul 2022
Cited by 7 | Viewed by 1963
Abstract
Adjuvants and delivery systems are essential components of vaccines to increase immunogenicity against target antigens, particularly for peptide epitopes (poor immunogens). Emulsions, nanoparticles, and liposomes are commonly used as a delivery system for peptide-based vaccines. A Poly(hydrophobic amino acids) delivery system was previously [...] Read more.
Adjuvants and delivery systems are essential components of vaccines to increase immunogenicity against target antigens, particularly for peptide epitopes (poor immunogens). Emulsions, nanoparticles, and liposomes are commonly used as a delivery system for peptide-based vaccines. A Poly(hydrophobic amino acids) delivery system was previously conjugated to Group A Streptococcus (GAS)-derived peptide epitopes, allowing the conjugates to self-assemble into nanoparticles with self adjuvanting ability. Their hydrophobic amino acid tail also serves as an anchoring moiety for the peptide epitope, enabling it to be integrated into the liposome bilayer, to further boost the immunological responses. Polyleucine-based conjugates were anchored to cationic liposomes using the film hydration method and administered to mice subcutaneously. The polyleucine-peptide conjugate, its liposomal formulation, and simple liposomal encapsulation of GAS peptide epitope induced mucosal (saliva IgG) and systemic (serum IgG, IgG1 and IgG2c) immunity in mice. Polyleucine acted as a potent liposome anchoring portion, which stimulated the production of highly opsonic antibodies. The absence of polyleucine in the liposomal formulation (encapsulated GAS peptide) induced high levels of antibody titers, but with poor opsonic ability against GAS bacteria. However, the liposomal formulation of the conjugated vaccine was no more effective than conjugates alone self-assembled into nanoparticles. Full article
(This article belongs to the Special Issue A Century of Vaccine Adjuvants: From 1920 to 2020 and Beyond)
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17 pages, 2337 KiB  
Article
GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A Streptococcus
by Elena Palmieri, Zoltán Kis, James Ozanne, Roberta Di Benedetto, Beatrice Ricchetti, Luisa Massai, Martina Carducci, Davide Oldrini, Gianmarco Gasperini, Maria Grazia Aruta, Omar Rossi, Cleo Kontoravdi, Nilay Shah, Fatme Mawas and Francesca Micoli
Vaccines 2022, 10(7), 1034; https://doi.org/10.3390/vaccines10071034 - 28 Jun 2022
Cited by 9 | Viewed by 1961
Abstract
Group A Streptococcus (GAS) causes about 500,000 annual deaths globally, and no vaccines are currently available. The Group A Carbohydrate (GAC), conserved across all GAS serotypes, conjugated to an appropriate carrier protein, represents a promising vaccine candidate. Here, we explored the possibility to [...] Read more.
Group A Streptococcus (GAS) causes about 500,000 annual deaths globally, and no vaccines are currently available. The Group A Carbohydrate (GAC), conserved across all GAS serotypes, conjugated to an appropriate carrier protein, represents a promising vaccine candidate. Here, we explored the possibility to use Generalized Modules for Membrane Antigens (GMMA) as an alternative carrier system for GAC, exploiting their intrinsic adjuvant properties. Immunogenicity of GAC-GMMA conjugate was evaluated in different animal species in comparison to GAC-CRM197; and the two conjugates were also compared from a techno-economic point of view. GMMA proved to be a good alternative carrier for GAC, resulting in a higher immune response compared to CRM197 in different mice strains, as verified by ELISA and FACS analyses. Differently from CRM197, GMMA induced significant levels of anti-GAC IgG titers in mice also in the absence of Alhydrogel. In rabbits, a difference in the immune response could not be appreciated; however, antibodies from GAC-GMMA-immunized animals showed higher affinity toward purified GAC antigen compared to those elicited by GAC-CRM197. In addition, the GAC-GMMA production process proved to be more cost-effective, making this conjugate particularly attractive for low- and middle-income countries, where this pathogen has a huge burden. Full article
(This article belongs to the Special Issue A Century of Vaccine Adjuvants: From 1920 to 2020 and Beyond)
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14 pages, 2371 KiB  
Article
Immune Enhancement by the Tetra-Peptide Hydrogel as a Promising Adjuvant for an H7N9 Vaccine against Highly Pathogenic H7N9 Virus
by Xiaoxin Wu, Songjia Tang, Zhehua Wang, Xiaoyun Ma, Lingjian Zhang, Fen Zhang, Lanlan Xiao, Shuai Zhao, Qian Li, Ying Wang, Qingjing Wang and Keda Chen
Vaccines 2022, 10(1), 130; https://doi.org/10.3390/vaccines10010130 - 17 Jan 2022
Cited by 4 | Viewed by 1918
Abstract
Background: Short peptide hydrogel was reported as a possible adjuvant for vaccines. In order to evaluate whether the Tetra-Peptide Hydrogel can be a promising adjuvant for an H7N9 vaccine against the highly pathogenic H7N9 virus, we conducted this study. Methods: Tetra-Peptide Hydrogels (D [...] Read more.
Background: Short peptide hydrogel was reported as a possible adjuvant for vaccines. In order to evaluate whether the Tetra-Peptide Hydrogel can be a promising adjuvant for an H7N9 vaccine against the highly pathogenic H7N9 virus, we conducted this study. Methods: Tetra-Peptide Hydrogels (D and L conformations) were prepared by a self-assembly system using a Naproxen acid modified tetra peptide of GFFY (Npx-GFFY). Mice received two immunizations with the D-Tetra-Peptide Hydrogel adjuvant vaccine, the L-Tetra-Peptide Hydrogel adjuvant vaccine, or the split vaccine. Fourteen days following the second dose, the mice were challenged with the highly pathogenic A/Guangdong/GZ8H002/2017(H7N9) virus. The mice were observed for signs of illness, weight loss, pathological alterations of the lung tissues and immune responses in the following 2 weeks. Results: The D/L-Tetra-Peptide Hydrogels resembled long bars with hinges on each other, with a diameter of ~10 nm. The H7N9 vaccine was observed to adhere to the hydrogel. All the unvaccinated mice were dead by 8 days post infection with H7N9. The mice immunized by the split H7N9 vaccine were protected against infection with H7N9. Mice immunized by D/L-Tetra-Peptide Hydrogel adjuvant vaccines experienced shorter symptomatic periods and their micro-neutralization titers were higher than in the split H7N9 vaccine at 2 weeks post infection. The hemagglutinating inhibition (HI) titer in the L-Tetra-Peptide Hydrogel adjuvant vaccine group was higher than that in the split H7N9 vaccine 1 week and 2 weeks post infection. The HI titer in the D-Tetra-Peptide Hydrogel adjuvant vaccine group was higher than that in the split H7N9 vaccine at 2 weeks post infection. Conclusion: The D/L Tetra-Peptide Hydrogels increased the protection of the H7N9 vaccine and could be promising adjuvants for H7N9 vaccines against highly pathogenic H7N9 virus. Full article
(This article belongs to the Special Issue A Century of Vaccine Adjuvants: From 1920 to 2020 and Beyond)
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17 pages, 11524 KiB  
Hypothesis
The Relative Positioning of B and T Cell Epitopes Drives Immunodominance
by Riccardo Biavasco and Marco De Giovanni
Vaccines 2022, 10(8), 1227; https://doi.org/10.3390/vaccines10081227 - 31 Jul 2022
Cited by 1 | Viewed by 2117
Abstract
Humoral immunity is crucial for protection against invading pathogens. Broadly neutralizing antibodies (bnAbs) provide sterilizing immunity by targeting conserved regions of viral variants and represent the goal of most vaccination approaches. While antibodies can be selected to bind virtually any region of a [...] Read more.
Humoral immunity is crucial for protection against invading pathogens. Broadly neutralizing antibodies (bnAbs) provide sterilizing immunity by targeting conserved regions of viral variants and represent the goal of most vaccination approaches. While antibodies can be selected to bind virtually any region of a given antigen, the consistent induction of bnAbs in the context of influenza and HIV has represented a major roadblock. Many possible explanations have been considered; however, none of the arguments proposed to date seem to fully recapitulate the observed counter-selection for broadly protective antibodies. Antibodies can influence antigen presentation by enhancing the processing of CD4 epitopes adjacent to the binding region while suppressing the overlapping ones. We analyze the relative positioning of dominant B and T cell epitopes in published antigens that elicit strong and poor humoral responses. In strong immunogenic antigens, regions bound by immunodominant antibodies are frequently adjacent to CD4 epitopes, potentially boosting their presentation. Conversely, poorly immunogenic regions targeted by bnAbs in HIV and influenza overlap with clusters of dominant CD4 epitopes, potentially conferring an intrinsic disadvantage for bnAb-bearing B cells in germinal centers. Here, we propose the theory of immunodominance relativity, according to which the relative positioning of immunodominant B and CD4 epitopes within a given antigen drives immunodominance. Thus, we suggest that the relative positioning of B-T epitopes may be one additional mechanism that cooperates with other previously described processes to influence immunodominance. If demonstrated, this theory can improve the current understanding of immunodominance, provide a novel explanation for HIV and influenza escape from humoral responses, and pave the way for a new rational design of universal vaccines. Full article
(This article belongs to the Special Issue A Century of Vaccine Adjuvants: From 1920 to 2020 and Beyond)
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