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Sublingual Immunotherapy as an Alternative to Induce Protection Against Acute Respiratory Infections
Published on: August 30, 2014
Single vector platform vaccine protects against lethal respiratory challenge with Tier 1 select agents of anthrax,
Qingmei Jia1, Richard Bowen2, Barbara Jane Dillon1
1Division of Infectious Diseases, Department of Medicine, 37-121 Center for Health Sciences, School of Medicine, University of California - Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA, 90095-1688, USA.
Abstract:
Bacillus anthracis, Yersinia pestis, and Francisella tularensis are the causative agents of Tier 1 Select Agents anthrax, plague, and tularemia, respectively. Currently, there are no licensed vaccines against plague and tularemia and the licensed anthrax vaccine is suboptimal. Here we report F. tularensis LVS ΔcapB (Live Vaccine Strain with a deletion in capB)- and attenuated multi-deletional Listeria monocytogenes (Lm)-vectored vaccines against all three aforementioned pathogens. We show that LVS ΔcapB- and Lm-vectored vaccines express recombinant B. anthracis, Y. pestis, and F. tularensis immunoprotective antigens in broth and in macrophage-like cells and are non-toxic in mice. Homologous priming-boosting with the LVS ΔcapB-vectored vaccines induces potent antigen-specific humoral and T-cell-mediated immune responses and potent protective immunity against lethal respiratory challenge with all three pathogens. Protection against anthrax was far superior to that obtained with the licensed AVA vaccine and protection against tularemia was comparable to or greater than that obtained with the toxic and unlicensed LVS vaccine. Heterologous priming-boosting with LVS ΔcapB- and Lm-vectored B. anthracis and Y. pestis vaccines also induced potent protective immunity against lethal respiratory challenge with B. anthracis and Y. pestis. The single vaccine platform, especially the LVS ΔcapB-vectored vaccine platform, can be extended readily to other pathogens.
Insights
New vaccines using attenuated bacteria express antigens from anthrax, plague, and tularemia pathogens. These novel vaccines provide potent protection against lethal respiratory challenges, offering a promising platform for future infectious disease prevention.
Area of Science:
- * Infectious disease research
- * Vaccinology
- * Microbial pathogenesis
Background:
- * Anthrax, plague, and tularemia are caused by Bacillus anthracis, Yersinia pestis, and Francisella tularensis, respectively.
- * Existing vaccines for anthrax are suboptimal, and no licensed vaccines exist for plague or tularemia.
- * There is a critical need for effective vaccines against these Tier 1 Select Agents.
Purpose of the Study:
- * To develop and evaluate novel vaccine candidates against anthrax, plague, and tularemia.
- * To assess the immunogenicity and protective efficacy of attenuated bacterial vaccine platforms.
- * To explore the potential of a single vaccine platform for multiple high-threat pathogens.
Main Methods:
- * Development of Francisella tularensis LVS ΔcapB and Listeria monocytogenes (Lm)-vectored vaccines expressing recombinant antigens.
- * In vitro expression analysis in broth and macrophage-like cells.
- * In vivo immunogenicity and protection studies in mice following homologous and heterologous prime-boost regimens.
- * Assessment of humoral and T-cell-mediated immune responses and survival after lethal respiratory challenge.
Main Results:
- * LVS ΔcapB- and Lm-vectored vaccines successfully expressed target antigens and were non-toxic in mice.
- * Homologous prime-boosting with LVS ΔcapB-vectored vaccines induced robust immune responses and significant protection against all three pathogens.
- * Vaccine efficacy against anthrax surpassed the licensed AVA vaccine, and against tularemia, it was comparable or superior to the unlicensed LVS vaccine.
- * Heterologous prime-boosting strategies also conferred potent protection against anthrax and plague.
Conclusions:
- * Attenuated LVS ΔcapB and Lm vaccine platforms are effective in expressing key antigens and inducing protective immunity against B. anthracis, Y. pestis, and F. tularensis.
- * The LVS ΔcapB-vectored vaccine demonstrates superior protection against anthrax and tularemia compared to existing vaccines.
- * This versatile vaccine platform shows potential for broad application against various infectious agents.
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