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Pharmaceutics
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Design and Evaluation of Molecular Adjuvants for Human and Veterinary...
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Design and Evaluation of Molecular Adjuvants for Human and Veterinary Vaccines

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: closed (20 June 2022) | Viewed by 22504

Special Issue Editors

Prof. Dr. Suh-Chin Wu

E-Mail Website
Guest Editor
1. Institute of Biotechnology, National Tsing Hua University, Hsinchu 30013, Taiwan
2. Department of Medical Science, National Tsing Hua University, Hsinchu 30013, Taiwan
Interests: viral vaccines; influenza virus; dengue virus; biotechnology
Special Issues, Collections and Topics in MDPI journals
Dr. Alexander Batista-Duharte

E-Mail Website
Guest Editor
Laboratório de Imunología Clínica, Dpto Analises Clinicas, Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (UNESP), Rod. Araraquara-Jaú-Km 1, Campus Ville, Araraquara, São Paulo 14800-903, Brazil
Interests: vaccine; adjuvants; immunotoxicity; immunopharmacology; immunomodulators for cancer; infectious; autoimmune and allergic diseases

Special Issue Information

Dear Colleagues,

The progressive replacement of conventional live attenuated and inactivated whole cell  vaccines with new generation of subunit vaccines based in purified, recombinant, syntetic and nucleic acid-based vaccines (DNA or RNA) has generally reduced reactogenicity but also immunogenicity. Therefore, adjuvants and delivery systems are key components that are used to optimize and to enhance the efficacy of vaccines. The majority of known adjuvants have been empirically identified any are often associated with adverse reactions. Adjuvant-induced toxicity considerably limits their use in human and veterinary vaccines. The reduced immunogenicity of new vaccine antigens and the need for safer vaccines have increased the importance of identifying single, well-defined adjuvants with known molecular targets and mechanisms of action for rational vaccine design.

This Special Issue focuses on current approaches and challenges to modulate the immune response with molecular adjuvants for vaccine improvement. This is a topic of intense current research in vaccinology

Prof. Dr. Suh-Chin Wu
Dr. Alexander Batista-Duharte
Guest Editors

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Keywords

  • vaccines
  • adjuvants
  • pattern-recognition-receptor agonists
  • immune checkpoint modulators
  • antisense oligonucleotides
  • recombinant and syntetic-based vaccines
  • nucleic acid-based vaccines
  • micro and nano-delivery systems

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Published Papers (6 papers)

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Research

Jump to: Review

18 pages, 2231 KiB  
Article
Intranasal Immunization with Zika Virus Envelope Domain III-Flagellin Fusion Protein Elicits Systemic and Mucosal Immune Responses and Protection against Subcutaneous and Intravaginal Virus Challenges
by Chi-Hsun Chen, Chung-Chu Chen, Wei-Bo Wang, Vania Lionel, Chia-Chyi Liu, Li-Min Huang and Suh-Chin Wu
Pharmaceutics 2022, 14(5), 1014; https://doi.org/10.3390/pharmaceutics14051014 - 8 May 2022
Cited by 10 | Viewed by 2760
Abstract
Zika virus (ZIKV) infections in humans are mainly transmitted by the mosquito vectors, but human-to-human sexual transmission is also another important route. Developing a ZIKV mucosal vaccine that can elicit both systemic and mucosal immune responses is of particular interest. In this study, [...] Read more.
Zika virus (ZIKV) infections in humans are mainly transmitted by the mosquito vectors, but human-to-human sexual transmission is also another important route. Developing a ZIKV mucosal vaccine that can elicit both systemic and mucosal immune responses is of particular interest. In this study, we constructed a recombinant ZIKV envelope DIII (ZDIII) protein genetically fused with Salmonella typhimurium flagellin (FliC-ZDIII) as a novel mucosal antigen for intranasal immunization. The results indicated that the FliC-ZDIII fusion proteins formulated with E. coli heat-labile enterotoxin B subunit (LTIIb-B5) adjuvant greatly increased the ZDIII-specific IgG, IgA, and neutralizing titers in sera, and the ZDIII-specific IgA titers in bronchoalveolar lavage and vaginal fluids. Protective immunity was further assessed by subcutaneous and intravaginal ZIKV challenges. The second-generation FliCΔD3-2ZDIII was shown to result in a reduced titer of anti-FliC IgG antibodies in sera and still retained the same levels of serum IgG, IgA, and neutralizing antibodies and mucosal IgA antibodies without compromising the vaccine antigenicity. Therefore, intranasal immunization with FliCΔD3-2ZDIII fusion proteins formulated with LTIIb-B5 adjuvant elicited the greatest protective immunity against subcutaneous and intravaginal ZIKV challenges. Our findings indicated that the combination of FliCΔD3-2ZDIII fusion proteins and LTIIb-B5 adjuvant for intranasal immunization can be used for developing ZIKV mucosal vaccines. Full article
(This article belongs to the Special Issue Design and Evaluation of Molecular Adjuvants for Human and Veterinary Vaccines)
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17 pages, 2264 KiB  
Article
A Polylactide-Based Micellar Adjuvant Improves the Intensity and Quality of Immune Response
by Myriam Lamrayah, Capucine Phelip, Céline Coiffier, Céline Lacroix, Thibaut Willemin, Thomas Trimaille and Bernard Verrier
Pharmaceutics 2022, 14(1), 107; https://doi.org/10.3390/pharmaceutics14010107 - 3 Jan 2022
Cited by 3 | Viewed by 2141
Abstract
Micelles from amphiphilic polylactide-block-poly(N-acryloxysuccinimide-co-N-vinylpyrrolidone) (PLA-b-P(NAS-co-NVP)) block copolymers of 105 nm in size were characterized and evaluated in a vaccine context. The micelles were non-toxic in vitro (both in dendritic cells and HeLa cells). In vitro [...] Read more.
Micelles from amphiphilic polylactide-block-poly(N-acryloxysuccinimide-co-N-vinylpyrrolidone) (PLA-b-P(NAS-co-NVP)) block copolymers of 105 nm in size were characterized and evaluated in a vaccine context. The micelles were non-toxic in vitro (both in dendritic cells and HeLa cells). In vitro fluorescence experiments combined with in vivo fluorescence tomography imaging, through micelle loading with the DiR near infrared probe, suggested an efficient uptake of the micelles by the immune cells. The antigenic protein p24 of the HIV-1 was successfully coupled on the micelles using the reactive N-succinimidyl ester groups on the micelle corona, as shown by SDS-PAGE analyses. The antigenicity of the coupled antigen was preserved and even improved, as assessed by the immuno-enzymatic (ELISA) test. Then, the performances of the micelles in immunization were investigated and compared to different p24-coated PLA nanoparticles, as well as Alum and MF59 gold standards, following a standardized HIV-1 immunization protocol in mice. The humoral response intensity (IgG titers) was substantially similar between the PLA micelles and all other adjuvants over an extended time range (one year). More interestingly, this immune response induced by PLA micelles was qualitatively higher than the gold standards and PLA nanoparticles analogs, expressed through an increasing avidity index over time (>60% at day 365). Taken together, these results demonstrate the potential of such small-sized micellar systems for vaccine delivery. Full article
(This article belongs to the Special Issue Design and Evaluation of Molecular Adjuvants for Human and Veterinary Vaccines)
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25 pages, 5836 KiB  
Article
Nano DNA Vaccine Encoding Toxoplasma gondii Histone Deacetylase SIR2 Enhanced Protective Immunity in Mice
by Zhengqing Yu, Yujia Lu, Wandi Cao, Muhammad Tahir Aleem, Junlong Liu, Jianxun Luo, Ruofeng Yan, Lixin Xu, Xiaokai Song and Xiangrui Li
Pharmaceutics 2021, 13(10), 1582; https://doi.org/10.3390/pharmaceutics13101582 - 29 Sep 2021
Cited by 5 | Viewed by 2470
Abstract
The pathogen of toxoplasmosis, Toxoplasma gondii (T. gondii), is a zoonotic protozoon that can affect the health of warm-blooded animals including humans. Up to now, an effective vaccine with completely protection is still inaccessible. In this study, the DNA vaccine encoding [...] Read more.
The pathogen of toxoplasmosis, Toxoplasma gondii (T. gondii), is a zoonotic protozoon that can affect the health of warm-blooded animals including humans. Up to now, an effective vaccine with completely protection is still inaccessible. In this study, the DNA vaccine encoding T. gondii histone deacetylase SIR2 (pVAX1-SIR2) was constructed. To enhance the efficacy, chitosan and poly (d, l-lactic-co-glycolic)-acid (PLGA) were employed to design nanospheres loaded with the DNA vaccine, denoted as pVAX1-SIR2/CS and pVAX1-SIR2/PLGA nanospheres. The pVAX1-SIR2 plasmids were transfected into HEK 293-T cells, and the expression was evaluated by a laser scanning confocal microscopy. Then, the immune protections of pVAX1-SIR2 plasmid, pVAX1-SIR2/CS nanospheres, and pVAX1-SIR2/PLGA nanospheres were evaluated in a laboratory animal model. The in vivo findings indicated that pVAX1-SIR2/CS and pVAX1-SIR2/PLGA nanospheres could generate a mixed Th1/Th2 immune response, as indicated by the regulated production of antibodies and cytokines, the enhanced maturation and major histocompatibility complex (MHC) expression of dendritic cells (DCs), the induced splenocyte proliferation, and the increased percentages of CD4+ and CD8+ T lymphocytes. Furthermore, this enhanced immunity could obviously reduce the parasite burden in immunized animals through a lethal dose of T. gondii RH strain challenge. All these results propose that pVAX1-SIR2 plasmids entrapped in chitosan or PLGA nanospheres could be the promising vaccines against acute T. gondii infections and deserve further investigations. Full article
(This article belongs to the Special Issue Design and Evaluation of Molecular Adjuvants for Human and Veterinary Vaccines)
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10 pages, 1186 KiB  
Article
Polymeric Caffeic Acid Acts as a Nasal Vaccine Formulation against Streptococcus pneumoniae Infections in Mice
by Rui Tada, Hidehiko Suzuki, Miki Ogasawara, Daisuke Yamanaka, Yoshiyuki Adachi, Jun Kunisawa and Yoichi Negishi
Pharmaceutics 2021, 13(4), 585; https://doi.org/10.3390/pharmaceutics13040585 - 20 Apr 2021
Cited by 8 | Viewed by 2744
Abstract
Infectious diseases are the second leading cause of death worldwide, highlighting the importance of the development of a novel and improved strategy for fighting pathogenic microbes. Streptococcus pneumoniae is a highly pathogenic bacteria that causes pneumonia with high mortality rates, especially in children [...] Read more.
Infectious diseases are the second leading cause of death worldwide, highlighting the importance of the development of a novel and improved strategy for fighting pathogenic microbes. Streptococcus pneumoniae is a highly pathogenic bacteria that causes pneumonia with high mortality rates, especially in children and elderly individuals. To solve these issues, a mucosal vaccine system would be the best solution for the prevention and treatment of these diseases. We have recently reported that enzymatically polymerized caffeic acid (pCA) acts as a mucosal adjuvant when co-administered with antigenic proteins via the nasal route. Moreover, the sources of caffeic acid and horseradish peroxidase are ingredients found commonly in coffee beans and horseradish, respectively. In this study, we aimed to develop a pneumococcal nasal vaccine comprising pneumococcal surface protein A (PspA) and pCA as the mucosal adjuvant. Intranasal immunization with PspA and pCA induced the production of PspA-specific antibody responses in the mucosal and systemic compartments. Furthermore, the protective effects were tested in a murine model of S. pneumoniae infection. Intranasal vaccination conferred antigen-dependent protective immunity against a lethal infection of S. pneumoniae. In conclusion, pCA is useful as a serotype-independent universal nasal pneumococcal vaccine formulation. Full article
(This article belongs to the Special Issue Design and Evaluation of Molecular Adjuvants for Human and Veterinary Vaccines)
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Review

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23 pages, 1128 KiB  
Review
Immune Checkpoint Inhibitors for Vaccine Improvements: Current Status and New Approaches
by Alexander Batista-Duharte, Fakhri Hassouneh, Pablo Alvarez-Heredia, Alejandra Pera and Rafael Solana
Pharmaceutics 2022, 14(8), 1721; https://doi.org/10.3390/pharmaceutics14081721 - 17 Aug 2022
Cited by 17 | Viewed by 3383
Abstract
In recent years, the use of immune checkpoint inhibitors (ICIs) in combination with approved or experimental vaccines has proven to be a promising approach to improve vaccine immunogenicity and efficacy. This strategy seeks to overcome the immunosuppressive mechanisms associated with the vaccine response, [...] Read more.
In recent years, the use of immune checkpoint inhibitors (ICIs) in combination with approved or experimental vaccines has proven to be a promising approach to improve vaccine immunogenicity and efficacy. This strategy seeks to overcome the immunosuppressive mechanisms associated with the vaccine response, thereby achieving increased immunogenicity and efficacy. Most of the information on the use of ICIs combined with vaccines derives from studies on certain anti-tumor vaccines combined with monoclonal antibodies (mAbs) against either cytotoxic T lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed death-ligand 1 (PD-L1). However, over the past few years, emerging strategies to use new-generation ICIs as molecular adjuvants are paving the way for future advances in vaccine research. Here, we review the current state and future directions of the use of ICIs in experimental and clinical settings, including mAbs and alternative new approaches using antisense oligonucleotides (ASOs), small non-coding RNAs, aptamers, peptides, and other small molecules for improving vaccine efficacy. The scope of this review mainly includes the use of ICIs in therapeutic antitumor vaccines, although recent research on anti-infective vaccines will also be addressed. Full article
(This article belongs to the Special Issue Design and Evaluation of Molecular Adjuvants for Human and Veterinary Vaccines)
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29 pages, 1316 KiB  
Review
Recent Advances in the Development of Toll-like Receptor Agonist-Based Vaccine Adjuvants for Infectious Diseases
by Jing-Xing Yang, Jen-Chih Tseng, Guann-Yi Yu, Yunping Luo, Chi-Ying F. Huang, Yi-Ren Hong and Tsung-Hsien Chuang
Pharmaceutics 2022, 14(2), 423; https://doi.org/10.3390/pharmaceutics14020423 - 16 Feb 2022
Cited by 58 | Viewed by 7421
Abstract
Vaccines are powerful tools for controlling microbial infections and preventing epidemic diseases. Efficient inactive, subunit, or viral-like particle vaccines usually rely on a safe and potent adjuvant to boost the immune response to the antigen. After a slow start, over the last decade [...] Read more.
Vaccines are powerful tools for controlling microbial infections and preventing epidemic diseases. Efficient inactive, subunit, or viral-like particle vaccines usually rely on a safe and potent adjuvant to boost the immune response to the antigen. After a slow start, over the last decade there has been increased developments on adjuvants for human vaccines. The development of adjuvants has paralleled our increased understanding of the molecular mechanisms for the pattern recognition receptor (PRR)-mediated activation of immune responses. Toll-like receptors (TLRs) are a group of PRRs that recognize microbial pathogens to initiate a host’s response to infection. Activation of TLRs triggers potent and immediate innate immune responses, which leads to subsequent adaptive immune responses. Therefore, these TLRs are ideal targets for the development of effective adjuvants. To date, TLR agonists such as monophosphoryl lipid A (MPL) and CpG-1018 have been formulated in licensed vaccines for their adjuvant activity, and other TLR agonists are being developed for this purpose. The COVID-19 pandemic has also accelerated clinical research of vaccines containing TLR agonist-based adjuvants. In this paper, we reviewed the agonists for TLR activation and the molecular mechanisms associated with the adjuvants’ effects on TLR activation, emphasizing recent advances in the development of TLR agonist-based vaccine adjuvants for infectious diseases. Full article
(This article belongs to the Special Issue Design and Evaluation of Molecular Adjuvants for Human and Veterinary Vaccines)
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