Novel Methods For Prevention & Control Of Influenza.

Overview

Influenza A viruses are significant human pathogens that cause widespread morbidity and mortality annually. There is an added concern that the highly virulent H5N1 subtype represents a serious public health threat and may result in a pandemic. Intervention strategies to halt an influenza epidemics and pandemics are a high priority, with an emphasis on vaccines and antiviral drugs. Increasing resistance to current antivirals and limited vaccine efficacy against H5N1 viruses supports the urgent need to identify and...
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Overview

Influenza A viruses are significant human pathogens that cause widespread morbidity and mortality annually. There is an added concern that the highly virulent H5N1 subtype represents a serious public health threat and may result in a pandemic. Intervention strategies to halt an influenza epidemics and pandemics are a high priority, with an emphasis on vaccines and antiviral drugs. Increasing resistance to current antivirals and limited vaccine efficacy against H5N1 viruses supports the urgent need to identify and characterize new methods for treatment and control of influenza. In the following studies, we demonstrate that a 20-amino-acid peptide, EB, exhibits broad-spectrum antiviral activity against influenza viruses. The EB peptide was protective in vivo in a mouse model, even when administered post-infection. The antiviral activity of EB is due to inhibition of virus attachment to host cells through induction of virion aggregation. We identified several truncations of the full-length EB peptide that retained antiviral activity. Deletions of up to 4 residues from the C-terminus and 8 from the N-terminus did not affect antiviral activity, while several of the truncations displayed enhanced activity. The truncated antiviral peptides aggregated influenza virus similar to full-length EB, while non-active peptides did not. Additionally, at least one truncation was identified that had virucidal properties when used at high concentrations. Finally, we expanded the potential uses of EB by applying it as a vaccine adjuvant for poorly immunogenic influenza subtypes. Mice receiving inactivated influenza virus vaccine with the inclusion of EB adjuvant showed less severe clinical signs of infection, recovered faster and showed enhanced viral clearance suggesting EB adjuvanted vaccine was superior to non-adjuvanted vaccine. This protection against challenge was not due to an enhanced humoral antibody response, but may be mediated by enhanced T-cell activity. Overall, the data generated in this thesis provide a foundation for development of EB peptide as a potent antiviral with applications for both prophylaxis and treatment of influenza infection.
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Product Details

  • ISBN-13: 9781243599780
  • Publisher: BiblioLabsII
  • Publication date: 9/4/2011
  • Pages: 100
  • Product dimensions: 7.44 (w) x 9.69 (h) x 0.21 (d)

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