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Vaccines
Special Issues
Immunological Mechanisms of Vaccines and Adjuvants
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Immunological Mechanisms of Vaccines and Adjuvants

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

Deadline for manuscript submissions: closed (31 January 2021) | Viewed by 20468

Special Issue Editors

Dr. Katie Ewer

E-Mail Website
Guest Editor
The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK
Interests: Malaria vaccines; pre-erythrocytic vaccines; Ebola vaccines; clinical trials; T cells; correlates of protection
Dr. Randy A. Albrecht

grade E-Mail Website1 Website2
Guest Editor
Department of Microbiology, Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
Interests: vaccines; mucosal immunity; respiratory viruses; pathogenesis; animal models; biocontainment
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are soliciting articles for this Special Issue of MDPI Vaccines, which is entitled “Immunological Mechanisms of Vaccines and Adjuvants”.

Vaccination is the most effective method of preventing and reducing the burden of infectious diseases. However, the effectiveness of many vaccines can be improved. Adjuvants increase immune responses to vaccine antigens. Thus, adjuvants are becoming increasingly attractive to improve the safety and effectiveness of vaccines.

An improved understanding of immune mechanisms of action for different classes of adjuvants will drive forward research and development of vaccines and adjuvants. This Special Issue of Vaccines is intended to bring together a collection of peer-reviewed articles on cutting-edge research on the immunological mechanisms of actions for adjuvants. We invite perspectives, review articles, and original research articles from specialists in host–pathogen interactions, host–vaccine interactions, vaccine or adjuvant development, host immune response, and clinical and/or preclinical trials.

Dr. Katie Ewer
Dr. Randy A. Albrecht
Guest Editors

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

  • vaccines
  • adjuvants
  • immunological mechanisms of action
  • immune-modulation
  • mucosal immunity
  • pathogen recognition receptors
  • pathogen-associated molecular patterns
  • animal models

Published Papers (5 papers)

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Research

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9 pages, 1493 KiB  
Article
Evidence for Anti-Viral Effects of Complete Freund’s Adjuvant in the Mouse Model of Enterovirus Infection
by Arunakumar Gangaplara, Chandirasegaran Massilamany, Ninaad Lasrado, David Steffen and Jay Reddy
Vaccines 2020, 8(3), 364; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines8030364 - 07 Jul 2020
Cited by 1 | Viewed by 2619
Abstract
Group B coxsackieviruses (CVBs) belonging to the genus, Enterovirus and contain six serotypes that induce various diseases, whose occurrence may involve the mediation of more than one serotype. We recently identified immunogenic epitopes within coxsackieviruses B3 (CVB3) viral protein 1 that induce anti-viral [...] Read more.
Group B coxsackieviruses (CVBs) belonging to the genus, Enterovirus and contain six serotypes that induce various diseases, whose occurrence may involve the mediation of more than one serotype. We recently identified immunogenic epitopes within coxsackieviruses B3 (CVB3) viral protein 1 that induce anti-viral T cell responses in mouse models of CVB infections. In our investigations to determine the protective responses of the viral epitopes, we unexpectedly noted that animals immunized with complete Freund’s adjuvant (CFA) alone and later challenged with CVB3 were completely protected against myocarditis. Similarly, the pancreatitis-inducing ability of CVB3 was remarkably reduced to only 10% in the CFA group as opposed to 73.3% in the control group that received no CFA. Additionally, no mortalities were noted in the CFA group, whereas 40% of control animals died during the course of 21 days post-infection with CVB3. Taken together, our data suggest that the adjuvant effects of CFA may be sufficient for protection against CVB infections. These observations may provide new insights into our understanding of the occurrence of viral infections. Full article
(This article belongs to the Special Issue Immunological Mechanisms of Vaccines and Adjuvants)
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16 pages, 3117 KiB  
Article
Simple Nanoparticles from the Assembly of Cationic Polymer and Antigen as Immunoadjuvants
by Yunys Pérez-Betancourt, Bianca de Carvalho Lins Fernandes Távora, Mônica Colombini, Eliana L. Faquim-Mauro and Ana Maria Carmona-Ribeiro
Vaccines 2020, 8(1), 105; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines8010105 - 28 Feb 2020
Cited by 18 | Viewed by 3974
Abstract
Since antigens are negatively charged, they combine well with positively charged adjuvants. Here, ovalbumin (OVA) (0.1 mg·mL−1) and poly (diallyldimethylammonium chloride) (PDDA) (0.01 mg·mL−1) yielded PDDA/OVA assemblies characterized by dynamic light scattering (DLS) and scanning electron microscopy (SEM) as [...] Read more.
Since antigens are negatively charged, they combine well with positively charged adjuvants. Here, ovalbumin (OVA) (0.1 mg·mL−1) and poly (diallyldimethylammonium chloride) (PDDA) (0.01 mg·mL−1) yielded PDDA/OVA assemblies characterized by dynamic light scattering (DLS) and scanning electron microscopy (SEM) as spherical nanoparticles (NPs) of 170 ± 4 nm hydrodynamic diameter, 30 ± 2 mV of zeta-potential and 0.11 ± 0.01 of polydispersity. Mice immunization with the NPs elicited high OVA-specific IgG1 and low OVA-specific IgG2a production, indicating a Th-2 response. Delayed-type hypersensitivity reaction (DTH) was low and comparable to the one elicited by Al(OH)3/OVA, suggesting again a Th-2 response. PDDA advantages as an adjuvant were simplicity (a single-component adjuvant), low concentration needed (0.01 mg·mL−1 PDDA) combined with antigen yielding neglectable cytotoxicity, and high stability of PDDA/OVA dispersions. The NPs elicited much higher OVA-specific antibodies production than Al(OH)3/OVA. In vivo, the nano-metric size possibly assured antigen presentation by antigen-presenting cells (APC) at the lymph nodes, in contrast to the location of Al(OH)3/OVA microparticles at the site of injection for longer periods with stimulation of local dendritic cells. In the future, it will be interesting to evaluate combinations of the antigen with NPs carrying both PDDA and elicitors of the Th-1 response. Full article
(This article belongs to the Special Issue Immunological Mechanisms of Vaccines and Adjuvants)
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21 pages, 6510 KiB  
Article
Mechanisms of Mixed Th1/Th2 Responses in Mice Induced by Albizia julibrissin Saponin Active Fraction by in Silico Analysis
by Jing Du, Junjie Jin, Juanjuan Wang and Hongxiang Sun
Vaccines 2020, 8(1), 48; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines8010048 - 27 Jan 2020
Cited by 5 | Viewed by 3731
Abstract
The purified active fraction of Albizia julibrissin saponin (AJSAF) is an ideal adjuvant candidate that improves antigen-specific both cellular and humoral immune responses and elicits mixed Th1/Th2 responses, but its mechanisms remain unclear. The key features of action of AJSAF were investigated in [...] Read more.
The purified active fraction of Albizia julibrissin saponin (AJSAF) is an ideal adjuvant candidate that improves antigen-specific both cellular and humoral immune responses and elicits mixed Th1/Th2 responses, but its mechanisms remain unclear. The key features of action of AJSAF were investigated in mice immunized with Newcastle disease virus-based recombinant influenza vaccine (rL-H5) and AJSAF at the same leg (AJSAF+rL-H5) or different legs (AJSAF/rL-H5). The adjuvant activity of AJSAF on rL-H5 is strictly dependent on their spatial colocalization. Serum H5 antigen (H5Ag)-specific IgG, IgG1, IgG2a, and IgG2b antibody titers in AJSAF+rL-H5 group were significantly higher than those in AJSAF/rL-H5 group. The mechanisms of selectivity of Th1 or Th2 in mice induced by AJSAF was explored by the transcriptomic and proteomic profiles of H5Ag-stimulated splenocytes from the immunized mice using gene microarray and two-dimensional difference gel electrophoresis coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Compared to rL-H5 alone, AJSAF/rL-H5 induced more differentially expressed genes (DEGs) than AJSAF+rL-H5, whereas AJSAF+rL-H5 upregulated higher mRNA expression of Th1 (T-bet, IFN-γ, TNF-α, IL-12β, and IL-12Rβ1) and Th2 (IL-10 and AICDA) immune response genes. The neutrophil response and its derived S100A8 and S100A9 might be involved in the AJSAF-mediated Th1 response. Meanwhile, AJSAF might induce the adaptive immune responses by improving a local innate immune microenvironment. These findings expanded the current knowledge on the mechanisms of action of saponin-based adjuvants, and provided new insights into how adjuvants shape adaptive immune responses. Full article
(This article belongs to the Special Issue Immunological Mechanisms of Vaccines and Adjuvants)
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14 pages, 2288 KiB  
Article
Essential Role of Host Double-Stranded DNA Released from Dying Cells by Cationic Liposomes for Mucosal Adjuvanticity
by Rui Tada, Akihiro Ohshima, Yuya Tanazawa, Akari Ohmi, Saeko Takahashi, Hiroshi Kiyono, Jun Kunisawa, Yukihiko Aramaki and Yoichi Negishi
Vaccines 2020, 8(1), 8; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines8010008 - 27 Dec 2019
Cited by 8 | Viewed by 3011
Abstract
Infectious disease remains a substantial cause of death. To overcome this issue, mucosal vaccine systems are considered to be a promising strategy. Yet, none are approved for clinical use, except for live-attenuated mucosal vaccines, mainly owing to the lack of effective and safe [...] Read more.
Infectious disease remains a substantial cause of death. To overcome this issue, mucosal vaccine systems are considered to be a promising strategy. Yet, none are approved for clinical use, except for live-attenuated mucosal vaccines, mainly owing to the lack of effective and safe systems to induce antigen-specific immune responses in the mucosal compartment. We have reported that intranasal vaccination of an antigenic protein, with cationic liposomes composed of 1,2-dioleoyl-3-trimethylammonium-propane and 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl], induced antigen-specific mucosal and systemic antibody responses in mice. However, precise molecular mechanism(s) underlying the mucosal adjuvant effects of cationic liposomes remain to be uncovered. Here, we show that a host double-stranded DNA (dsDNA), released at the site of cationic liposome injection, plays an essential role for the mucosal adjuvanticity of the cationic liposome. Namely, we found that nasal administration of the cationic liposomes induced localized cell death, at the site of injection, resulting in extracellular leakage of host dsDNA. Additionally, in vivo DNase I treatment markedly impaired OVA-specific mucosal and systemic antibody production exerted by cationic liposomes. Our report reveals that host dsDNA, released from local dying cells, acts as a damage-associated molecular pattern that mediates the mucosal adjuvant activity of cationic liposomes. Full article
(This article belongs to the Special Issue Immunological Mechanisms of Vaccines and Adjuvants)
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Review

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25 pages, 1731 KiB  
Review
Inflammasome-Mediated Immunogenicity of Clinical and Experimental Vaccine Adjuvants
by Sören Reinke, Aneesh Thakur, Cillian Gartlan, Jelena S. Bezbradica and Anita Milicic
Vaccines 2020, 8(3), 554; https://0-doi-org.brum.beds.ac.uk/10.3390/vaccines8030554 - 22 Sep 2020
Cited by 35 | Viewed by 6111
Abstract
In modern vaccines, adjuvants can be sophisticated immunological tools to promote robust and long-lasting protection against prevalent diseases. However, there is an urgent need to improve immunogenicity of vaccines in order to protect mankind from life-threatening diseases such as AIDS, malaria or, most [...] Read more.
In modern vaccines, adjuvants can be sophisticated immunological tools to promote robust and long-lasting protection against prevalent diseases. However, there is an urgent need to improve immunogenicity of vaccines in order to protect mankind from life-threatening diseases such as AIDS, malaria or, most recently, COVID-19. Therefore, it is important to understand the cellular and molecular mechanisms of action of vaccine adjuvants, which generally trigger the innate immune system to enhance signal transition to adaptive immunity, resulting in pathogen-specific protection. Thus, improved understanding of vaccine adjuvant mechanisms may aid in the design of “intelligent” vaccines to provide robust protection from pathogens. Various commonly used clinical adjuvants, such as aluminium salts, saponins or emulsions, have been identified as activators of inflammasomes - multiprotein signalling platforms that drive activation of inflammatory caspases, resulting in secretion of pro-inflammatory cytokines of the IL-1 family. Importantly, these cytokines affect the cellular and humoral arms of adaptive immunity, which indicates that inflammasomes represent a valuable target of vaccine adjuvants. In this review, we highlight the impact of different inflammasomes on vaccine adjuvant-induced immune responses regarding their mechanisms and immunogenicity. In this context, we focus on clinically relevant adjuvants that have been shown to activate the NLRP3 inflammasome and also present various experimental adjuvants that activate the NLRP3-, NLRC4-, AIM2-, pyrin-, or non-canonical inflammasomes and could have the potential to improve future vaccines. Together, we provide a comprehensive overview on vaccine adjuvants that are known, or suggested, to promote immunogenicity through inflammasome-mediated signalling. Full article
(This article belongs to the Special Issue Immunological Mechanisms of Vaccines and Adjuvants)
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