Pandemic Influenza Vaccine Research

The ultimate goal of this research is to develop nonpathogenic replication-defective adenoviral vector-based vaccines that rapidly induce long-lasting and broad immunity against a number of pandemic strains of IFV. The genetic reassortment between human and avian IFVs can result in a virus with a novel HA, typically of avian origin, against which humans lack immunity. In the 20th century, the pandemics of 1918, 1957, and 1968 were the result of such antigenic shifts. The recent outbreaks of avian influenza caused by H5N1, H7N7 and H9N2 IFVs with infections of humans have created a new awareness of the pandemic potential of IFVs that circulate in domestic poultry. These events highlight the need for vaccines against influenza that confer cross-protection against pandemic strains, subtypes with pandemic potential, and new drift variants. The estimated economic impact of a pandemic would be up to $166.5 billion in the United States alone, with 200,000 deaths, 730,000 hospitalizations, 42 million outpatient visits, and 50 million additional illnesses. In the context of prevailing threats of global bioterrorism, terrorists deliberately infected with a highly virulent IFV preparation could act as difficult-to-detect biological weapons of mass destruction.

Publications

Vemula SV, Amen O, Katz JM, Donis R, Sambhara S and Mittal SK.( 2013) Beta-defensin 2 enhances immunogenicity and protection of an adenovirus-based H5N1 influenza vaccine at an early time. Virus Res. 178:(2): 398-403.  PUBMED

Vemula SV, Pandey A, Singh N, Katz JM, Donis R, Sambhara S and Mittal SK. 2013. Adenoviral vector expressing murine beta-defensin 2 enhances immunogenicity of an adenoviral vector based H5N1 influenza vaccine in aged mice. Virus Res. 177:55-61. PUBMED

Vemula SV, Ahi YS, Swaim AM, Katz JM, Donis R, Sambhara S and Mittal SK. 2013. Broadly protective adenovirus-based multivalent vaccines against highly pathogenic avian influenza viruses for pandemic preparedness. PLoS.One. 8:(4): e62496-. PUBMED

Vemula S and Mittal SK. (2010). Production of adenovirus vectors and their use as a delivery system for influenza vaccines. Expert Opin Biol Ther. 10(10):1469-87. PUBMED

Singh N, Pandey A, Sambhara S and Mittal SK. (2010). Avian influenza pandemic preparedness: developing prepandemic and pandemic vaccines against a moving target. Expert Reviews in Molecular Medicine.Apr 29;12:e14. PUBMED

Pandey A, Singh N, Sambhara S and Suresh K. Mittal. (2009). Egg-independent vaccine strategies for highly pathogenic H5N1 influenza viruses. Human Vaccine. 2010 6(2):178-188. PUBMED

Singh N, Pandey A, Jayashankar L and Mittal SK. (2008). Bovine adenoviral vector-based H5N1 influenza vaccine overcomes exceptionally high levels of pre-existing immunity against human adenovirus. Mol. Ther. 16(5):965-971 PUBMED

Hoelscher MA, Singh N, Garg S, Jayashankar L, Veguilla V, Pandey A, Matsuoka Y, Katz JM, Donis R, Mittal SK and Sambhara S. (2008). A broadly-protective pandemic influenza vaccine against clade 1 and clade 2 H5N1 viruses. J. Infect. Dis. 197(8):1185-8 PUBMED

Hoelscher MA, Jayashankar L, Garg S, Veguilla V, Lu X, Singh N, Katz JM,Mittal SK and Sambhara S. (2007).New pre-pandemic influenza vaccines: An egg- and adjuvant-independent human adenoviral vector strategy induces long lasting protective immune responses in mice. Clin. Pharmacol. Ther. 82:665-671. PUBMED

Hoelscher MA, Garg S, Bangari DS, et al. (2006). Development of adenoviral-vector-based pandemic influenza vaccine against antigenically distinct human H5N1 strains in mice. Lancet . 367(9509):475-81.PUBMED

 

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