Background: Existing anthrax postexposure antibiotic treatments are inadequate because they do not clear the high levels of secreted anthrax toxins. Results: Susceptible cells treated with anthrax toxin receptor-targeted siRNAs became resistant to anthrax toxin-mediated cytotoxicity. Conclusion: RNAi-targeted silencing of anthrax toxin receptors prevents toxins from entering target cells and inducing pathogenesis. Significance: Toxin receptor-targeted RNAi can be developed as a postexposure treatment against anthrax.
Preventive influenza vaccines must be reformulated annually because of antigen shift and drift of circulating influenza viral strains. However, seasonal vaccines do not always match the circulating strains, and there is the ever-present threat that avian influenza viruses may adapt to humans. Hence, a universal influenza vaccine is needed to provide protective immunity against a broad range of influenza viruses. We designed an influenza antigen consisting of three tandem M2e repeats plus HA2, in combination with a detoxified anthrax oedema toxin delivery system (EFn plus PA) to enhance immune responses. The EFn-3×M2e-HA2 plus PA vaccine formulation elicited robust, antigen-specific, IgG responses; and was protective against heterologous influenza viral challenge when intranasally delivered to mice three times. Moreover, use of the detoxified anthrax toxin system as an adjuvant had the additional benefit of generating protective immunity against anthrax. Hence, this novel vaccine strategy could potentially address two major emerging public health and biodefence threats.
Influenza remains to be a significant public health problem worldwide, despite the heavy campaign for flu vaccination in many countries. The conventional influenza vaccines are based on stimulating immune responses against hemagglutinin by virus attenuation or inactivation. However, they must be reformulated annually because of antigenic shift and drift of circulating influenza viral strains. These seasonal vaccines do not always match the circulating strains, and there is the ever-present threat that avian influenza viruses may adapt to be transmitted in humans. Development of a broadly protective or universal influenza vaccine would have a significant impact on public health. We constructed a new chimeric influenza antigen, which is composed of the relatively conserved matrix protein 2 (M2) and stem region of hemagglutinin (HA2) of influenza A viruses in combination with a detoxified anthrax edema toxin delivery system. This vaccine candidate has been shown to elicit T cell and humoral responses against influenza antigens and cross-strain protective immunity against influenza viruses, when it is intranasally delivered to mice. In addition, the vaccination of CD4+ and CD8+ T cell knock out mice do not protect against influenza virus infection. Thus, this novel vaccine strategy induces the CD4+ and CD8+ memory T cell responses which play an important role in cross-strain protection against influenza viruses.
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