Vaccines

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Open AccessEditorial

Vaccine Formulation for Infectious Diseases and Adjuvant Mechanisms of Action

by Heather L. Wilson, Azita Haddadi and George K. Mutwiri

Vaccines 2021, 9(6), 667; https://doi.org/10.3390/vaccines9060667 - 18 Jun 2021

Cited by 1 | Viewed by 2012

Abstract

The ultimate goal for vaccination is the generation of a safe and effective immune response that protects against diseases [...] Full article

(This article belongs to the Special Issue Vaccine Formulation for Infectious Diseases and Adjuvant Mechanisms of Action)

Research

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15 pages, 1377 KiB

Open AccessArticle

The Adjuvants Polyphosphazene (PCEP) and a Combination of Curdlan Plus Leptin Promote a Th17-Type Immune Response to an Intramuscular Vaccine in Mice

by Alyssa Chaffey, Glenn Hamonic, Dylan Chand, George K. Mutwiri and Heather L. Wilson

Vaccines 2021, 9(5), 507; https://doi.org/10.3390/vaccines9050507 - 14 May 2021

Cited by 4 | Viewed by 3591

Abstract

Our aim was to determine whether polyphosphazene (PCEP), Curdlan (β-glucan, a dectin-1 agonist), and Leptin could act as adjuvants to promote a Th17-type adaptive immune response in mice. Mice were vaccinated via the intramuscular route then boosted three weeks later with Ovalbumin plus: [...] Read more.

Our aim was to determine whether polyphosphazene (PCEP), Curdlan (β-glucan, a dectin-1 agonist), and Leptin could act as adjuvants to promote a Th17-type adaptive immune response in mice. Mice were vaccinated via the intramuscular route then boosted three weeks later with Ovalbumin plus: PCEP, Leptin, Curdlan, PCEP+Curdlan, Curdlan+Leptin, or saline. Mice vaccinated with OVA+PCEP and OVA+Curdlan+Leptin showed significantly higher frequency of antigen-specific CD4+ T cells secreting IL-17 relative to OVA-vaccinated mice. No formulation increased the frequency of CD4+ T cells secreting IL-4 or IFNγ. Since activation of innate immunity precedes the development of adaptive immunity, we wished to establish whether induction of Th17-type immunity could be predicted from in vitro experiments and/or from the local cytokine environment after immunization with adjuvants alone. Elevated IL-6 and TGFβ with reduced secretion of IL-12 is a cytokine milieu known to promote differentiation of Th17-type immunity. We injected the immunostimulants or saline buffer into murine thigh muscles and measured acute local cytokine production. PCEP induced significant production of IL-6 and reduced IL-12 production in muscle but it did not lead to elevated TGFβ production. Curdlan+Leptin injected into muscle induced significant production of TGFβ and IL-17 but not IL-6 or IL-12. We also stimulated splenocytes with media or PCEP, Leptin, Curdlan, PCEP+Curdlan, Curdlan+Leptin, PCEP+Leptin, and PCEP+Curdlan+Leptin and measured cytokine production. PCEP stimulation of splenocytes failed to induce significant production of IL-6, IL-12, TGFβ, or IL-17 and therefore ex vivo splenocyte stimulation failed to predict the increased frequency of Th17-type T cells in response to the vaccine. Curdlan-stimulated splenocytes produced Th1-type, inducing cytokine, IL-12. Curdlan+/-PCEP stimulated TGF-β production and Curdlan+Leptin+/- PCEP induced secretion of IL-17. We conclude that PCEP as well as Curdlan+Leptin are Th17-type vaccine adjuvants in mice but that cytokines produced in response to these adjuvants in muscle after injection or in ex vivo cultured splenocytes did not predict their role as a Th17-type adjuvant. Together, these data suggest that the cytokine environments induced by these immunostimulants did not predict induction of an antigen-specific Th17-type adaptive immune response. This is the first report of these adjuvants inducing a Th17-type adaptive immune response. Full article

(This article belongs to the Special Issue Vaccine Formulation for Infectious Diseases and Adjuvant Mechanisms of Action)

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13 pages, 1472 KiB

Open AccessArticle

Immunogenicity of Varicella-Zoster Virus Glycoprotein E Formulated with Lipid Nanoparticles and Nucleic Immunostimulators in Mice

by Han Cao, Yunfei Wang, Ning Luan and Cunbao Liu

Vaccines 2021, 9(4), 310; https://doi.org/10.3390/vaccines9040310 - 25 Mar 2021

Cited by 14 | Viewed by 4836

Abstract

Theoretically, the subunit herpes zoster vaccine Shingrix^TM could be used as a varicella vaccine that avoids the risk of developing shingles from vaccination, but bedside mixing strategies and the limited supply of the adjuvant component QS21 have made its application economically impracticable. [...] Read more.

Theoretically, the subunit herpes zoster vaccine Shingrix^TM could be used as a varicella vaccine that avoids the risk of developing shingles from vaccination, but bedside mixing strategies and the limited supply of the adjuvant component QS21 have made its application economically impracticable. With lipid nanoparticles (LNPs) that were approved by the FDA as vectors for severe acute respiratory syndrome coronavirus 2 vaccines, we designed a series of vaccines efficiently encapsulated with varicella-zoster virus glycoprotein E (VZV-gE) and nucleic acids including polyinosinic-polycytidylic acid (Poly I:C) and the natural phosphodiester CpG oligodeoxynucleotide (CpG ODN), which was approved by the FDA as an immunostimulator in a hepatitis B vaccine. Preclinical trial in mice showed that these LNP vaccines could induce VZV-gE IgG titers more than 16 times those induced by an alum adjuvant, and immunized serum could block in vitro infection completely at a dilution of 1:80, which indicated potential as a varicella vaccine. The magnitude of the cell-mediated immunity induced was generally more than 10 times that induced by the alum adjuvant, indicating potential as a zoster vaccine. These results showed that immunostimulatory nucleic acids together with LNPs have promise as safe and economical varicella and zoster vaccine candidates. Full article

(This article belongs to the Special Issue Vaccine Formulation for Infectious Diseases and Adjuvant Mechanisms of Action)

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18 pages, 2697 KiB

Open AccessArticle

Silicone Oil-Based Nanoadjuvants as Candidates for a New Formulation of Intranasal Vaccines

by Agnieszka Razim, Marcelina Pyclik, Katarzyna Pacyga, Sabina Górska, Jintao Xu, Michal A. Olszewski, Andrzej Gamian and Andrzej Myc

Vaccines 2021, 9(3), 234; https://doi.org/10.3390/vaccines9030234 - 8 Mar 2021

Cited by 5 | Viewed by 3139

Abstract

Many conventional vaccines are administered via a needle injection, while most pathogens primarily invade the host via mucosal surfaces. Moreover, protective IgA antibodies are insufficiently induced by parenteral vaccines. Mucosal immunity induces both local and systemic response to pathogens and typically lasts for [...] Read more.

Many conventional vaccines are administered via a needle injection, while most pathogens primarily invade the host via mucosal surfaces. Moreover, protective IgA antibodies are insufficiently induced by parenteral vaccines. Mucosal immunity induces both local and systemic response to pathogens and typically lasts for long periods of time. Therefore, vaccination via mucosal routes has been increasingly explored. However, mucosal vaccines require potent adjuvants to become efficacious. Despite many efforts to develop safe and robust adjuvants for mucosal vaccines, only a few have been approved for use in human formulations. The aim of our study was to design, develop and characterize new silicone oil-based nanoadjuvant candidates for intranasal vaccines with potential to become mucosal adjuvants. We have developed an array of nanoadjuvant candidates (NACs), based on well-defined ingredients. NAC1, 2 and 3 are based on silicone oil, but differ in the used detergents and organic solvents, which results in variations in their droplet size and zeta potential. NACs’ cytotoxicity, Tumor Necrosis Factor α (TNF-α) induction and their effect on antigen engulfment by immune cells were tested in vitro. Adjuvant properties of NACs were verified by intranasal vaccination of mice together with ovalbumin (OVA). NACs show remarkable stability and do not require any special storage conditions. They exhibit bio-adhesiveness and influence the degree of model protein engulfment by epithelial cells. Moreover, they induce high specific anti-OVA IgG antibody titers after two intranasal administrations. Nanoadjuvant candidates composed of silicone oil and cationic detergents are stable, exhibit remarkable adjuvant properties and can be used as adjuvants for intranasal immunization. Full article

(This article belongs to the Special Issue Vaccine Formulation for Infectious Diseases and Adjuvant Mechanisms of Action)

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13 pages, 2328 KiB

Open AccessArticle

Novel Inactivated Subtype B Avian Metapneumovirus Vaccine Induced Humoral and Cellular Immune Responses

by Yuanling Bao, Mengmeng Yu, Peng Liu, Fujun Hou, Farooque Muhammad, Zhihao Wang, Xinyi Li, Zhuo Zhang, Suyan Wang, Yuntong Chen, Hongyu Cui, Aijing Liu, Xiaole Qi, Qing Pan, Yanping Zhang, Li Gao, Kai Li, Changjun Liu, Xijun He, Xiaomei Wang and Yulong Gao Show full author list Hide full author list

Vaccines 2020, 8(4), 762; https://doi.org/10.3390/vaccines8040762 - 14 Dec 2020

Cited by 6 | Viewed by 2772

Abstract

Avian metapneumovirus (aMPV), a highly contagious agent, is widespread and causes acute upper respiratory tract disease in chickens and turkeys. However, currently, there is no vaccine licensed in China. Herein, we describe the development of an inactivated aMPV/B vaccine using the aMPV/B strain [...] Read more.

Avian metapneumovirus (aMPV), a highly contagious agent, is widespread and causes acute upper respiratory tract disease in chickens and turkeys. However, currently, there is no vaccine licensed in China. Herein, we describe the development of an inactivated aMPV/B vaccine using the aMPV/B strain LN16. Combined with a novel adjuvant containing immune-stimulating complexes (ISCOMs), the novel vaccine could induce high virus-specific and VN antibodies. In addition, it activated B and T lymphocytes and promoted the expression of IL-4 and IFN-γ. Importantly, boosting vaccination with the inactivated aMPV/B vaccine could provide 100% protection against aMPV/B infection with reduced virus shedding and turbinate inflammation. The protection efficacy could last for at least 6 months. This study yielded a novel inactivated aMPV/B vaccine that could serve as the first vaccine candidate in China, thus contributing to the control of aMPV/B and promoting the development of the poultry industry. Full article

(This article belongs to the Special Issue Vaccine Formulation for Infectious Diseases and Adjuvant Mechanisms of Action)

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17 pages, 5155 KiB

Open AccessArticle

Repurposing of Miltefosine as an Adjuvant for Influenza Vaccine

by Lu Lu, Carol Ho-Yan Fong, Anna Jinxia Zhang, Wai-Lan Wu, Iris Can Li, Andrew Chak-Yiu Lee, Thrimendra Kaushika Dissanayake, Linlei Chen, Ivan Fan-Ngai Hung, Kwok-Hung Chan, Hin Chu, Kin-Hang Kok, Kwok-Yung Yuen and Kelvin Kai-Wang To

Vaccines 2020, 8(4), 754; https://doi.org/10.3390/vaccines8040754 - 11 Dec 2020

Cited by 7 | Viewed by 3354

Abstract

We previously reported that topical imiquimod can improve the immunogenicity of the influenza vaccine. This study investigated another FDA-approved drug, miltefosine (MTF), as a vaccine adjuvant. Mice immunized with an influenza vaccine with or without MTF adjuvant were challenged by a lethal dose [...] Read more.

We previously reported that topical imiquimod can improve the immunogenicity of the influenza vaccine. This study investigated another FDA-approved drug, miltefosine (MTF), as a vaccine adjuvant. Mice immunized with an influenza vaccine with or without MTF adjuvant were challenged by a lethal dose of influenza virus 3 or 7 days after vaccination. Survival, body weight, antibody response, histopathological changes, viral loads, cytokine levels, and T cell frequencies were compared. The MTF-adjuvanted vaccine (MTF-VAC) group had a significantly better survival rate than the vaccine-only (VAC) group, when administered 3 days (80% vs. 26.7%, p = 0.0063) or 7 days (96% vs. 65%, p = 0.0041) before influenza virus challenge. Lung damage was significantly ameliorated in the MTF-VAC group. Antibody response was significantly augmented in the MTF-VAC group against both homologous and heterologous influenza strains. There was a greater T follicular helper cell (T_FH) response and an enhanced germinal center (GC) reaction in the MTF-VAC group. MTF-VAC also induced both T_H1 and T_H2 antigen-specific cytokine responses. MTF improved the efficacy of the influenza vaccine against homologous and heterologous viruses by improving the T_FH and antibody responses. Miltefosine may also be used for other vaccines, including the upcoming vaccines for COVID-19. Full article

(This article belongs to the Special Issue Vaccine Formulation for Infectious Diseases and Adjuvant Mechanisms of Action)

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10 pages, 1231 KiB

Open AccessArticle

Combination of Innate Immune Modulators as Vaccine Adjuvants in Mice

by Azita Haddadi, Alyssa Chaffey, Siew Hon Ng, Damayanthi Yalamati and Heather L. Wilson

Vaccines 2020, 8(4), 569; https://doi.org/10.3390/vaccines8040569 - 1 Oct 2020

Cited by 6 | Viewed by 2959

Abstract

The development of new, effective, and safe vaccines necessarily requires the identification of new adjuvant(s) to enhance the potency and longevity of antigen-specific immune responses. In the present study, we compare the antibody-mediated and cell-mediated immune (CMI) responses within groups of mice vaccinated [...] Read more.

The development of new, effective, and safe vaccines necessarily requires the identification of new adjuvant(s) to enhance the potency and longevity of antigen-specific immune responses. In the present study, we compare the antibody-mediated and cell-mediated immune (CMI) responses within groups of mice vaccinated subcutaneously with ovalbumin (OVA; as an experimental antigen) plus polyphosphazene (an innate immune modulator), Polyinosinic:polycytidylic acid (poly-I:C; (an RNA mimetic) and glycopeptide ARC5 (which is a Toll-like receptor (TLR), TLR2 ligand and PAM3CSK4 analogue) formulated together in a soluble vaccine. We also investigated the effect of a polymeric nanoparticle of ARC4 and ARC7 (which are a novel muramyl dipeptide analogue and a monophosophoryl lipid A (MPLA) analogue, respectively) plus OVA +/− ARC5 as a subcutaneous vaccine in mice. OVA+ARC4/ARC7 nanoparticle +/− ARC5 triggered a robust and balanced Th1/Th2-type humoral response with significant anti-OVA IgA in serum, and significant interferon (IFN)-γ and interleukin (IL)-17 production in splenocytes after 35 days relative to the controls. Formulation of OVA with ARC4/ARC7 nanoparticles should be investigated for inducing protective immunity against infectious pathogens in mice and other species. Full article

(This article belongs to the Special Issue Vaccine Formulation for Infectious Diseases and Adjuvant Mechanisms of Action)

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12 pages, 1003 KiB

Open AccessArticle

Adjuvant Activity of Synthetic Lipid A of Alcaligenes, a Gut-Associated Lymphoid Tissue-Resident Commensal Bacterium, to Augment Antigen-Specific IgG and Th17 Responses in Systemic Vaccine

by Yunru Wang, Koji Hosomi, Atsushi Shimoyama, Ken Yoshii, Haruki Yamaura, Takahiro Nagatake, Tomomi Nishino, Hiroshi Kiyono, Koichi Fukase and Jun Kunisawa

Vaccines 2020, 8(3), 395; https://doi.org/10.3390/vaccines8030395 - 20 Jul 2020

Cited by 19 | Viewed by 3567

Abstract

Alcaligenes spp. are identified as commensal bacteria and have been found to inhabit Peyer’s patches in the gut. We previously reported that Alcaligenes-derived lipopolysaccharides (LPS) exerted adjuvant activity in systemic vaccination, without excessive inflammation. Lipid A is one of the components responsible [...] Read more.

Alcaligenes spp. are identified as commensal bacteria and have been found to inhabit Peyer’s patches in the gut. We previously reported that Alcaligenes-derived lipopolysaccharides (LPS) exerted adjuvant activity in systemic vaccination, without excessive inflammation. Lipid A is one of the components responsible for the biological effect of LPS and has previously been applied as an adjuvant. Here, we examined the adjuvant activity and safety of chemically synthesized Alcaligenes lipid A. We found that levels of OVA-specific serum IgG antibodies increased in mice that were subcutaneously immunized with ovalbumin (OVA) plus Alcaligenes lipid A relative to those that were immunized with OVA alone. In addition, Alcaligenes lipid A promoted antigen-specific T helper 17 (Th17) responses in the spleen; upregulated the expression of MHC class II, CD40, CD80, and CD86 on bone marrow-derived dendritic cells (BMDCs); enhanced the production of Th17-inducing cytokines IL-6 and IL-23 from BMDCs. Stimulation with Alcaligenes lipid A also induced the production of IL-6 and IL-1β in human peripheral blood mononuclear cells. Moreover, Alcaligenes lipid A caused minor side effects, such as lymphopenia and thrombocytopenia. These findings suggest that Alcaligenes lipid A is a safe and effective Th17-type adjuvant by directly stimulating dendritic cells in systemic vaccination. Full article

(This article belongs to the Special Issue Vaccine Formulation for Infectious Diseases and Adjuvant Mechanisms of Action)

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Review

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51 pages, 4230 KiB

Open AccessReview

Interferon-Based Biopharmaceuticals: Overview on the Production, Purification, and Formulation

by Leonor S. Castro, Guilherme S. Lobo, Patrícia Pereira, Mara G. Freire, Márcia C. Neves and Augusto Q. Pedro

Vaccines 2021, 9(4), 328; https://doi.org/10.3390/vaccines9040328 - 1 Apr 2021

Cited by 19 | Viewed by 10425

Abstract

The advent of biopharmaceuticals in modern medicine brought enormous benefits to the treatment of numerous human diseases and improved the well-being of many people worldwide. First introduced in the market in the early 1980s, the number of approved biopharmaceutical products has been steadily [...] Read more.

The advent of biopharmaceuticals in modern medicine brought enormous benefits to the treatment of numerous human diseases and improved the well-being of many people worldwide. First introduced in the market in the early 1980s, the number of approved biopharmaceutical products has been steadily increasing, with therapeutic proteins, antibodies, and their derivatives accounting for most of the generated revenues. The success of pharmaceutical biotechnology is closely linked with remarkable developments in DNA recombinant technology, which has enabled the production of proteins with high specificity. Among promising biopharmaceuticals are interferons, first described by Isaacs and Lindenmann in 1957 and approved for clinical use in humans nearly thirty years later. Interferons are secreted autocrine and paracrine proteins, which by regulating several biochemical pathways have a spectrum of clinical effectiveness against viral infections, malignant diseases, and multiple sclerosis. Given their relevance and sustained market share, this review provides an overview on the evolution of interferon manufacture, comprising their production, purification, and formulation stages. Remarkable developments achieved in the last decades are herein discussed in three main sections: (i) an upstream stage, including genetically engineered genes, vectors, and hosts, and optimization of culture conditions (culture media, induction temperature, type and concentration of inducer, induction regimens, and scale); (ii) a downstream stage, focusing on single- and multiple-step chromatography, and emerging alternatives (e.g., aqueous two-phase systems); and (iii) formulation and delivery, providing an overview of improved bioactivities and extended half-lives and targeted delivery to the site of action. This review ends with an outlook and foreseeable prospects for underdeveloped aspects of biopharma research involving human interferons. Full article

(This article belongs to the Special Issue Vaccine Formulation for Infectious Diseases and Adjuvant Mechanisms of Action)

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18 pages, 2296 KiB

Open AccessReview

Natural and Synthetic Saponins as Vaccine Adjuvants

by Pengfei Wang

Vaccines 2021, 9(3), 222; https://doi.org/10.3390/vaccines9030222 - 5 Mar 2021

Cited by 68 | Viewed by 9317

Abstract

Saponin adjuvants have been extensively studied for their use in veterinary and human vaccines. Among them, QS-21 stands out owing to its unique profile of immunostimulating activity, inducing a balanced Th1/Th2 immunity, which is valuable to a broad scope of applications in combating [...] Read more.

Saponin adjuvants have been extensively studied for their use in veterinary and human vaccines. Among them, QS-21 stands out owing to its unique profile of immunostimulating activity, inducing a balanced Th1/Th2 immunity, which is valuable to a broad scope of applications in combating various microbial pathogens, cancers, and other diseases. It has recently been approved for use in human vaccines as a key component of combination adjuvants, e.g., AS01b in Shingrix^® for herpes zoster. Despite its usefulness in research and clinic, the cellular and molecular mechanisms of QS-21 and other saponin adjuvants are poorly understood. Extensive efforts have been devoted to studies for understanding the mechanisms of QS-21 in different formulations and in different combinations with other adjuvants, and to medicinal chemistry studies for gaining mechanistic insights and development of practical alternatives to QS-21 that can circumvent its inherent drawbacks. In this review, we briefly summarize the current understandings of the mechanism underlying QS-21’s adjuvanticity and the encouraging results from recent structure-activity-relationship (SAR) studies. Full article

(This article belongs to the Special Issue Vaccine Formulation for Infectious Diseases and Adjuvant Mechanisms of Action)

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13 pages, 260 KiB

Open AccessReview

Understanding GroEL and DnaK Stress Response Proteins as Antigens for Bacterial Diseases

by Kezia R. Fourie and Heather L. Wilson

Vaccines 2020, 8(4), 773; https://doi.org/10.3390/vaccines8040773 - 17 Dec 2020

Cited by 41 | Viewed by 3868

Abstract

Bacteria do not simply express a constitutive panel of proteins but they instead undergo dynamic changes in their protein repertoire in response to changes in nutritional status and when exposed to different environments. These differentially expressed proteins may be suitable to use for [...] Read more.

Bacteria do not simply express a constitutive panel of proteins but they instead undergo dynamic changes in their protein repertoire in response to changes in nutritional status and when exposed to different environments. These differentially expressed proteins may be suitable to use for vaccine antigens if they are virulence factors. Immediately upon entry into the host organism, bacteria are exposed to a different environment, which includes changes in temperature, osmotic pressure, pH, etc. Even when an organism has already penetrated the blood or lymphatics and it then enters another organ or a cell, it can respond to these new conditions by increasing the expression of virulence factors to aid in bacterial adherence, invasion, or immune evasion. Stress response proteins such as heat shock proteins and chaperones are some of the proteins that undergo changes in levels of expression and/or changes in cellular localization from the cytosol to the cell surface or the secretome, making them potential immunogens for vaccine development. Herein we highlight literature showing that intracellular chaperone proteins GroEL and DnaK, which were originally identified as playing a role in protein folding, are relocated to the cell surface or are secreted during invasion and therefore may be recognized by the host immune system as antigens. In addition, we highlight literature showcasing the immunomodulation effects these proteins can have on the immune system, also making them potential adjuvants or immunotherapeutics. Full article

(This article belongs to the Special Issue Vaccine Formulation for Infectious Diseases and Adjuvant Mechanisms of Action)

19 pages, 1109 KiB

Open AccessReview

The Age of Cyclic Dinucleotide Vaccine Adjuvants

by Himanshu Gogoi, Samira Mansouri and Lei Jin

Vaccines 2020, 8(3), 453; https://doi.org/10.3390/vaccines8030453 - 13 Aug 2020

Cited by 57 | Viewed by 5683

Abstract

As prophylactic vaccine adjuvants for infectious diseases, cyclic dinucleotides (CDNs) induce safe, potent, long-lasting humoral and cellular memory responses in the systemic and mucosal compartments. As therapeutic cancer vaccine adjuvants, CDNs induce potent anti-tumor immunity, including cytotoxic T cells and NK cells activation [...] Read more.

As prophylactic vaccine adjuvants for infectious diseases, cyclic dinucleotides (CDNs) induce safe, potent, long-lasting humoral and cellular memory responses in the systemic and mucosal compartments. As therapeutic cancer vaccine adjuvants, CDNs induce potent anti-tumor immunity, including cytotoxic T cells and NK cells activation that achieve durable regression in multiple mouse models of tumors. Clinical trials are ongoing to fulfill the promise of CDNs (ClinicalTrials.gov: NCT02675439, NCT03010176, NCT03172936, and NCT03937141). However, in October 2018, the first clinical data with Merck’s CDN MK-1454 showed zero activity as a monotherapy in patients with solid tumors or lymphomas (NCT03010176). Lately, the clinical trial from Aduro’s CDN ADU-S100 monotherapy was also disappointing (NCT03172936). The emerging hurdle in CDN vaccine development calls for a timely re-evaluation of our understanding on CDN vaccine adjuvants. Here, we review the status of CDN vaccine adjuvant research, including their superior adjuvant activities, in vivo mode of action, and confounding factors that affect their efficacy in humans. Lastly, we discuss the strategies to overcome the hurdle and advance promising CDN adjuvants in humans. Full article

(This article belongs to the Special Issue Vaccine Formulation for Infectious Diseases and Adjuvant Mechanisms of Action)

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