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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 17555

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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

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Keywords

infectious disease
vaccines
adjuvants
immunopotentiators
immunomodulators
mechanisms

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Published Papers (9 papers)

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Research

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18 pages, 2971 KiB

Open AccessArticle

Efficacy of LaAg Vaccine Associated with Saponin Against Leishmania amazonensis Infection

by Mirian França de Mello, Patrícia de Almeida Machado, Pollyanna Stephanie Gomes, Gabriel Oliveira-Silva, Monique Pacheco Duarte Carneiro, Tadeu Diniz Ramos, Juliana Elena Silveira Pratti, Raquel Peralva, Luan Firmino-Cruz, Alda Maria Da-Cruz, Luciana Covre, Daniel Claúdio Oliveira Gomes, Bartira Rossi-Bergmann, Eduardo Fonseca Pinto, Alessandra Marcia da Fonseca-Martins and Herbert Leonel de Matos Guedes

Vaccines 2025, 13(2), 129; https://doi.org/10.3390/vaccines13020129 - 27 Jan 2025

Viewed by 859

Abstract

Background/Objectives: The total lysate of Leishmania amazonensis (LaAg) is one of the most extensively studied vaccine formulations against leishmaniasis. Despite demonstrating safety and immunogenicity when administered intramuscularly, LaAg has failed to show efficacy in clinical trials and, in some cases, has even been associated with an enhanced susceptibility to infection. Adjuvants, which are molecules or compounds added to antigens to enhance the immunogenicity or modulate the immune response, are frequently employed in vaccine studies. This study aimed to evaluate different adjuvants to improve the protective efficacy of LaAg in L.amazonensis infection using a BALB/c mouse model. Methods: BALB/c mice were immunized with LaAg in combination with various adjuvants. The delayed-type hypersensitivity (DTH) test was assessed by measuring the infected paw and was used to evaluate the immunogenicity and to determine the most effective adjuvant. The immune response was analyzed through flow cytometry, focusing on cytokine production, immune cell recruitment and lesion size, alongside the control of parasite load at the infection site. The expression levels of iNOS and TGF-β were quantified using RT-qPCR, while IgG1, IgG2a and IgE antibody levels were determined via ELISA. Results: Among the adjuvants tested, only saponin (SAP) elicited a significant DTH response following LaAg challenge. SAP enhanced the immunogenicity of LaAg, as evidenced by increased IFN-γ-producing CD4⁺ and CD8⁺ T cells in the draining lymph nodes at 18 h post-challenge. Additionally, SAP facilitated the recruitment of lymphocytes, macrophages, neutrophils and eosinophils to the infection site. Conclusions: The LaAg + SAP combination conferred partial protection, as demonstrated by a reduction in lesion size and the partial control of parasite load. In conclusion, the addition of SAP as an adjuvant to LaAg effectively modulates the immune response, enhancing the vaccine’s protective efficacy. These findings provide valuable insights into the development of improved vaccines against L.amazonensis infection. Full article

(This article belongs to the Special Issue Recent Advances in Vaccine Adjuvants and Formulation)

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18 pages, 3148 KiB

Open AccessArticle

Evaluating the Compatibility of Three Aluminum Salt-Adjuvanted Recombinant Protein Antigens (Trivalent NRRV) Combined with a Mock Trivalent Sabin-IPV Vaccine: Analytical and Formulation Challenges

by Prashant Kumar, Atsushi Hamana, Christopher Bird, Brandy Dotson, Soraia Saleh-Birdjandi, David B. Volkin and Sangeeta B. Joshi

Vaccines 2024, 12(10), 1102; https://doi.org/10.3390/vaccines12101102 - 26 Sep 2024

Cited by 1 | Viewed by 1489

Abstract

In this work, we describe compatibility assessments of a recombinant, trivalent non-replicating rotavirus vaccine (t-NRRV) candidate with a mock trivalent Sabin inactivated polio vaccine (t-sIPV). Both t-sIPV and t-NRRV are incompatible with thimerosal (TH), a preservative commonly used in pediatric pentavalent combination vaccines (DTwP-Hib-HepB) distributed in low- and middle-income countries (LMICs), preventing the development of a heptavalent combination. The compatibility of t-NRRV with a mock DTwP-Hib-HepB formulation is described in a companion paper. This case study highlights the analytical and formulation challenges encountered when combining a mock t-sIPV vaccine (unadjuvanted) with Alhydrogel^® (AH) adjuvanted t-NRRV. Selective and stability-indicating competition ELISAs were implemented to monitor antibody binding to each of the six antigens (±AH). Simple mixing caused the undesired desorption of t-NRRV from AH with the concomitant binding of t-sIPV to AH. Although the former effect was mitigated by dialyzing sIPV bulks, decreased sIPV storage stability was observed at accelerated temperatures in the bivalent combination with a rank-ordering of P[8] > P[6] > P[4] and sIPV3 > sIPV2 > sIPV1. The compatibility of AH-adsorbed t-sIPV with alternative preservatives was evaluated, and parabens (methyl, propyl) were identified for potential use in this multi-dose bivalent formulation. Along with a companion paper, the lessons learned are discussed to facilitate the future formulation development of pediatric combination vaccines with new antigens. Full article

(This article belongs to the Special Issue Recent Advances in Vaccine Adjuvants and Formulation)

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18 pages, 2607 KiB

Open AccessArticle

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 1686

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 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

Open AccessArticle

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

Cited by 2 | Viewed by 1677

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 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

Open AccessArticle

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

Cited by 3 | Viewed by 2345

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 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

Open AccessArticle

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

Cited by 2 | Viewed by 2492

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 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

Open AccessArticle

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 2160

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 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

Open AccessArticle

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 3084

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 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, DTH^pos patients exhibit a 53.1% three-year survival compared to 16.1% in DTH^neg patients. Extended remissions are observed in long-term survivors, particularly DTH^pos/M1c^neg 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 M1c^neg/DTH^pos 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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17 pages, 2282 KiB

Open AccessReview

Host–Pathogen Interaction Interface: Promising Candidate Targets for Vaccine-Induced Protective and Memory Immune Responses

by Gloria G. Guerrero, Vicente Madrid-Marina, Aurora Martínez-Romero, Kirvis Torres-Poveda and Juan Manuel Favela-Hernández

Vaccines 2025, 13(4), 418; https://doi.org/10.3390/vaccines13040418 - 16 Apr 2025

Viewed by 554

Abstract

Vaccine formulations are a successful strategy against pathogen transmission because vaccine candidates induce effective and long-lasting memory immune responses (B and CD4+ T cells) at systemic and mucosal sites. Extracellular vesicles of lipoproteins, bioactive compounds from plants and invertebrates (sponges) encapsulated in liposomes, and glycoproteins can target these sites. The vaccine candidates developed can mimic microbial pathogens in a way that successfully links the innate and adaptive immune responses. In addition, vaccines plus adjuvants promote and maintain an inflammatory response. In this review, we aimed to identify the host–pathogen interface as a rich source of candidate targets for vaccine-induced protective and long-lasting memory immune responses. Full article

(This article belongs to the Special Issue Recent Advances in Vaccine Adjuvants and Formulation)

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