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Vaccines
Special Issues
Recent Advances in Vaccine Adjuvants and Formulation
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Recent Advances in Vaccine Adjuvants and Formulation

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

Deadline for manuscript submissions: 30 April 2025 | Viewed by 8824

Special Issue Editors

Dr. Aihua Zhao

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Guest Editor
1. Division of Tuberculosis Vaccine and Allergen Products, Institute of Biological Product Control, National Institutes for Food and Drug Control, Beijing 102629, China
2. Key Laboratory for Quality Research and Evaluation of Biological Products, National Medical Products Administration (NMPA), Beijing 102629, China
Interests: infectious disease; allergens; vaccine quality control; novel adjuvants and formulations
Dr. Junli Li

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Guest Editor Assistant
1. Division of Tuberculosis Vaccine and Allergen Products, Institute of Biological Product Control, National Institutes for Food and Drug Control, Beijing 102629, China
2. Key Laboratory for Quality Research and Evaluation of Biological Products, National Medical Products Administration (NMPA), Beijing 102629, China
Interests: TB; TB vaccines; TB animal models; adjuvants and delivery platforms

Special Issue Information

Dear Colleagues,

Vaccines are essential in eradicating or controlling many infectious diseases. However, there is still an urgent need for vaccines that fully stimulate cellular, long-lasting immunity, and even mucosal immunity. In addition, due to the uniqueness of each disease and the specific types of immune responses to be modulated, various kinds of novel adjuvants are needed to induce optimal immune responses against a particular disease. In the last two decades, compound adjuvants, especially in different formulations based on traditional aluminum adjuvant sources, have gained much interest in the generation of new vaccines since they can integrate all components and synergistically enhance the advantages of innate and adaptive immune responses.

Therefore, on this topic, we invite the submission of original and review articles which focus on novel vaccine adjuvants and attain their nature, formulation, delivery, mode of action, beneficial and adverse effects, quality control, and induced immune responses to accomplish efficient and long-lasting protection against infectious diseases.

Dr. Aihua Zhao
Guest Editor

Dr. Junli Li
Guest Editor Assistant

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

  • infectious disease
  • vaccines
  • adjuvants
  • immunopotentiators
  • immunomodulators
  • mechanisms

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Published Papers (6 papers)

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Research

18 pages, 2607 KiB  
Article
Intranasal Delivery of Quillaja brasiliensis Saponin-Based Nanoadjuvants Improve Humoral Immune Response of Influenza Vaccine in Aged Mice
by Fernando Silveira, Florencia García, Gabriel García, José A. Chabalgoity, Silvina Rossi and Mariana Baz
Vaccines 2024, 12(8), 902; https://doi.org/10.3390/vaccines12080902 - 9 Aug 2024
Viewed by 760
Abstract
Increasing the effectiveness of vaccines against respiratory viruses is particularly relevant for the elderly, since they are prone to develop serious infections due to comorbidities and the senescence of the immune system. The addition of saponin-based adjuvants is an interesting strategy to increase [...] Read more.
Increasing the effectiveness of vaccines against respiratory viruses is particularly relevant for the elderly, since they are prone to develop serious infections due to comorbidities and the senescence of the immune system. The addition of saponin-based adjuvants is an interesting strategy to increase the effectiveness of vaccines. We have previously shown that ISCOM matrices from Q. brasiliensis (IMXQB) are a safe and potent adjuvant. In this study, we evaluated the use of IMXQB as an adjuvant for the seasonal trivalent influenza vaccine (TIV) in an aged mice model. Herein, we show that subcutaneous injection of the adjuvanted vaccine promoted higher titers of IgM, IgG (and isotypes), and serum hemagglutination inhibition titers (HAI). Notably, aged mice immunized by intranasal route also produced higher IgG (and isotypes) and IgA titers up to 120 days after priming, as well as demonstrating an improvement in the HAI antibodies against the TIV. Further, experimental infected aged mice treated once with sera from adult naïve mice previously immunized with TIV-IMXQB subcutaneously successfully controlled the infection. Overall, TIV-IMXQB improved the immunogenicity compared to TIV by enhancing systemic and mucosal immunity in old mice conferring a faster recovery after the H1N1pdm09-like virus challenge. Thus, IMXQB nanoparticles may be a promising platform for next-generation viral vaccines. Full article
(This article belongs to the Special Issue Recent Advances in Vaccine Adjuvants and Formulation)
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13 pages, 3945 KiB  
Article
Enhanced Immune Responses in Mice by Combining the Mpox Virus B6R-Protein and Aluminum Hydroxide-CpG Vaccine Adjuvants
by Junli Li, Xiaochi Li, Jiaxin Dong, Jiazheng Wei, Xiaonan Guo, Guozhi Wang, Miao Xu and Aihua Zhao
Vaccines 2024, 12(7), 776; https://doi.org/10.3390/vaccines12070776 - 15 Jul 2024
Viewed by 858
Abstract
Novel adjuvants and innovative combinations of adjuvants (Adjuvant Systems) have facilitated the development of enhanced and new vaccines against re-emerging and challenging pathogenic microorganisms. Nonetheless, the efficacy of adjuvants is influenced by various factors, and the same adjuvant may generate entirely different immune [...] Read more.
Novel adjuvants and innovative combinations of adjuvants (Adjuvant Systems) have facilitated the development of enhanced and new vaccines against re-emerging and challenging pathogenic microorganisms. Nonetheless, the efficacy of adjuvants is influenced by various factors, and the same adjuvant may generate entirely different immune responses when paired with different antigens. Herein, we combined the MPXV-B6R antigen with BC02, a novel adjuvant with proprietary technology, to assess its capability to induce both cellular and humoral immunity in mouse models. Mice received two intramuscular injections of B6R-BC02, which resulted in the production of MPXV-specific IgG, IgG1, and IgG2a antibodies. Additionally, it elicited strong MPXV-specific Th1-oriented cellular immunity and persistent effector memory B-cell responses. The advantages of BC02 were further validated, including rapid initiation of the immune response, robust recall memory, and sustained immune response induction. Although the potential of immunized mice to produce serum-neutralizing antibodies against the vaccinia virus requires further improvement, the exceptional performance of BC02 as an adjuvant for the MPXV-B6R antigen has been consistently demonstrated. Full article
(This article belongs to the Special Issue Recent Advances in Vaccine Adjuvants and Formulation)
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16 pages, 2931 KiB  
Article
Molecular Events in Immune Responses to Sublingual Influenza Vaccine with Hemagglutinin Antigen and Poly(I:C) Adjuvant in Nonhuman Primates, Cynomolgus Macaques
by Tetsuro Yamamoto, Makoto Hirano, Fusako Mitsunaga, Kunihiko Wasaki, Atsushi Kotani, Kazuki Tajima and Shin Nakamura
Vaccines 2024, 12(6), 643; https://doi.org/10.3390/vaccines12060643 - 8 Jun 2024
Viewed by 1449
Abstract
Sublingual vaccines offer the benefits of inducing mucosal immunity to protect against respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and influenza, while also enabling needle-free self-administration. In a previous study, a sublingual SARS-CoV-2 vaccination was created by combining a recombinafigureCoV-2 [...] Read more.
Sublingual vaccines offer the benefits of inducing mucosal immunity to protect against respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and influenza, while also enabling needle-free self-administration. In a previous study, a sublingual SARS-CoV-2 vaccination was created by combining a recombinafigureCoV-2 spike protein receptor-binding domain antigen with a double strand RNA Poly(I:C) adjuvant. This vaccine was tested on nonhuman primates, Cynomolgus macaques. This study examined the immune and inflammatory responses elicited by the sublingual influenza vaccine containing hemagglutinin (HA) antigen and Poly(I:C) adjuvants, and assessed the safety of this vaccine in nonhuman primates. The Poly(I:C)-adjuvanted sublingual vaccine induced both mucosal and systemic immunities. Specifically, the sublingual vaccine produced HA-specific secretory IgA antibodies in saliva and nasal washings, and HA-specific IgA and IgG were detected in the blood. This vaccine appeared to be safe, as judged from the results of blood tests and plasma C-reactive protein levels. Notably, sublingual vaccination neither increased the production of inflammation-associated cytokines—IFN-alpha, IFN-gamma, and IL-17—in the blood, nor upregulated the gene expression of proinflammatory cytokines—IL12A, IL12B, IFNA1, IFNB1, CD69, and granzyme B—in white blood cells. Moreover, DNA microarray analyses revealed that sublingual vaccination evoked both enhancing and suppressing expression changes in genes associated with immune-related responses in cynomolgus monkeys. Therefore, the sublingual vaccine with the Poly(I:C) adjuvant is safe, and creates a balanced state of enhancing and suppressing the immune-related response. Full article
(This article belongs to the Special Issue Recent Advances in Vaccine Adjuvants and Formulation)
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25 pages, 4692 KiB  
Article
Evaluating the Compatibility of New Recombinant Protein Antigens (Trivalent NRRV) with a Mock Pentavalent Combination Vaccine Containing Whole-Cell Pertussis: Analytical and Formulation Challenges
by Prashant Kumar, David A. Holland, Kathryn Secrist, Poorva Taskar, Brandy Dotson, Soraia Saleh-Birdjandi, Yetunde Adewunmi, Jennifer Doering, Nicholas J. Mantis, David B. Volkin and Sangeeta B. Joshi
Vaccines 2024, 12(6), 609; https://doi.org/10.3390/vaccines12060609 - 3 Jun 2024
Viewed by 1478
Abstract
Introducing new recombinant protein antigens to existing pediatric combination vaccines is important in improving coverage and affordability, especially in low- and middle-income countries (LMICs). This case-study highlights the analytical and formulation challenges encountered with three recombinant non-replicating rotavirus vaccine (NRRV) antigens (t-NRRV formulated [...] Read more.
Introducing new recombinant protein antigens to existing pediatric combination vaccines is important in improving coverage and affordability, especially in low- and middle-income countries (LMICs). This case-study highlights the analytical and formulation challenges encountered with three recombinant non-replicating rotavirus vaccine (NRRV) antigens (t-NRRV formulated with Alhydrogel® adjuvant, AH) combined with a mock multidose formulation of a pediatric pentavalent vaccine used in LMICs. This complex formulation contained (1) vaccine antigens (i.e., whole-cell pertussis (wP), diphtheria (D), tetanus (T), Haemophilus influenza (Hib), and hepatitis B (HepB), (2) a mixture of aluminum-salt adjuvants (AH and Adju-Phos®, AP), and (3) a preservative (thimerosal, TH). Selective, stability-indicating competitive immunoassays were developed to monitor binding of specific mAbs to each antigen, except wP which required the setup of a mouse immunogenicity assay. Simple mixing led to the desorption of t-NRRV antigens from AH and increased degradation during storage. These deleterious effects were caused by specific antigens, AP, and TH. An AH-only pentavalent formulation mitigated t-NRRV antigen desorption; however, the Hib antigen displayed previously reported AH-induced instability. The same rank-ordering of t-NRRV antigen stability (P[8] > P[4] > P[6]) was observed in mock pentavalent formulations and with various preservatives. The lessons learned are discussed to enable future multidose, combination vaccine formulation development with new vaccine candidates. Full article
(This article belongs to the Special Issue Recent Advances in Vaccine Adjuvants and Formulation)
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22 pages, 6016 KiB  
Article
A Combined LC-MS and Immunoassay Approach to Characterize Preservative-Induced Destabilization of Human Papillomavirus Virus-like Particles Adsorbed to an Aluminum-Salt Adjuvant
by Ria T. Caringal, John M. Hickey, Nitya Sharma, Kaushal Jerajani, Oluwadara Bewaji, Sarah Brendle, Neil Christensen, Saurabh Batwal, Mustafa Mahedvi, Harish Rao, Vikas Dogar, Rahul Chandrasekharan, Umesh Shaligram, Sangeeta B. Joshi and David B. Volkin
Vaccines 2024, 12(6), 580; https://doi.org/10.3390/vaccines12060580 - 26 May 2024
Viewed by 1315
Abstract
During the multi-dose formulation development of recombinant vaccine candidates, protein antigens can be destabilized by antimicrobial preservatives (APs). The degradation mechanisms are often poorly understood since available analytical tools are limited due to low protein concentrations and the presence of adjuvants. In this [...] Read more.
During the multi-dose formulation development of recombinant vaccine candidates, protein antigens can be destabilized by antimicrobial preservatives (APs). The degradation mechanisms are often poorly understood since available analytical tools are limited due to low protein concentrations and the presence of adjuvants. In this work, we evaluate different analytical approaches to monitor the structural integrity of HPV16 VLPs adsorbed to Alhydrogel™ (AH) in the presence and absence of APs (i.e., destabilizing m-cresol, MC, or non-destabilizing chlorobutanol, CB) under accelerated conditions (pH 7.4, 50 °C). First, in vitro potency losses displayed only modest correlations with the results from two commonly used methods of protein analysis (SDS-PAGE, DSC). Next, results from two alternative analytical approaches provided a better understanding of physicochemical events occurring under these same conditions: (1) competitive ELISA immunoassays with a panel of mAbs against conformational and linear epitopes on HPV16 VLPs and (2) LC-MS peptide mapping to evaluate the accessibility/redox state of the 12 cysteine residues within each L1 protein comprising the HPV16 VLP (i.e., with 360 L1 proteins per VLP, there are 4320 Cys residues per VLP). These methods expand the limited analytical toolset currently available to characterize AH-adsorbed antigens and provide additional insights into the molecular mechanism(s) of AP-induced destabilization of vaccine antigens. Full article
(This article belongs to the Special Issue Recent Advances in Vaccine Adjuvants and Formulation)
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19 pages, 2071 KiB  
Article
Long-Term Survival and Immune Response Dynamics in Melanoma Patients Undergoing TAPCells-Based Vaccination Therapy
by Andrés Tittarelli, Cristian Pereda, María A. Gleisner, Mercedes N. López, Iván Flores, Fabián Tempio, Alvaro Lladser, Adnane Achour, Fermín E. González, Claudia Durán-Aniotz, Juan P. Miranda, Milton Larrondo and Flavio Salazar-Onfray
Vaccines 2024, 12(4), 357; https://doi.org/10.3390/vaccines12040357 - 27 Mar 2024
Viewed by 2006
Abstract
Cancer vaccines present a promising avenue for treating immune checkpoint blockers (ICBs)-refractory patients, fostering immune responses to modulate the tumor microenvironment. We revisit a phase I/II trial using Tumor Antigen-Presenting Cells (TAPCells) (NCT06152367), an autologous antigen-presenting cell vaccine loaded with heat-shocked allogeneic melanoma [...] Read more.
Cancer vaccines present a promising avenue for treating immune checkpoint blockers (ICBs)-refractory patients, fostering immune responses to modulate the tumor microenvironment. We revisit a phase I/II trial using Tumor Antigen-Presenting Cells (TAPCells) (NCT06152367), an autologous antigen-presenting cell vaccine loaded with heat-shocked allogeneic melanoma cell lysates. Initial findings showcased TAPCells inducing lysate-specific delayed-type hypersensitivity (DTH) reactions, correlating with prolonged survival. Here, we extend our analysis over 15 years, categorizing patients into short-term (<36 months) and long-term (≥36 months) survivors, exploring novel associations between clinical outcomes and demographic, genetic, and immunologic parameters. Notably, DTHpos patients exhibit a 53.1% three-year survival compared to 16.1% in DTHneg patients. Extended remissions are observed in long-term survivors, particularly DTHpos/M1cneg patients. Younger age, stage III disease, and moderate immune events also benefit short-term survivors. Immunomarkers like increased C-type lectin domain family 2 member D on CD4+ T cells and elevated interleukin-17A were detected in long-term survivors. In contrast, toll-like receptor-4 D229G polymorphism and reduced CD32 on B cells are associated with reduced survival. TAPCells achieved stable long remissions in 35.2% of patients, especially M1cneg/DTHpos cases. Conclusions: Our study underscores the potential of vaccine-induced immune responses in melanoma, emphasizing the identification of emerging biological markers and clinical parameters for predicting long-term remission. Full article
(This article belongs to the Special Issue Recent Advances in Vaccine Adjuvants and Formulation)
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