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Drs. Kevin Legge and Thomas Waldschmidt receive a five-year research grant from the National Institutes of Health

Drs. Thomas Waldschmidt, Kevin Legge, Balaji Manicassamy and Balaji Narasimhan Drs. Kevin Legge and Thomas Waldschmidt received a five-year NIH R01 research grant entitled “Protection and Immunity after Polyanhydride Nanoparticle Vaccination against Avian Influenza A Virus” from the National Institute of Allergy and Infectious Diseases (NIAID).

Seasonal Influenza A Virus (IAV) infections lead to approximately 200,000 hospitalizations and 36,000 deaths annually in the United States during non-pandemic years. Furthermore, the IAV pandemics of 1918 (~50 million deaths worldwide), 1957-58 (~1 million deaths worldwide) and 1968-69 (~700,000 deaths worldwide) further demonstrate the impact of IAV on human health. The recent appearance of highly pathogenic avian strains of IAV such as H5N1, H5N2 and H7N9 present a new threat given the high mortality rates observed in humans accidently infected with these viruses (~55-60% mortality rate). Although avian IAV currently does not spread human-to-human via air droplets, the acquisition of additional mutations could lead to this means of transmission resulting in a deadly pandemic.

Recent studies have shown that influenza vaccine strategies capable of inducing local (i.e. nasal mucosa and lung) tissue-resident memory T and B cells, in addition to systemic immunity, offer the greatest protection against future heterologous IAV encounters, including avian strains. By their design, currently licensed IAV-vaccines do not induce lung resident memory T and B cell responses and hence offer only homologous protection. For these reasons, the NIH/NIAID identified the generation of broadly protective vaccines against IAV as a high priority and released a Strategic Plan to achieve this goal.

Drs. Legge and Waldschmidt, along with key collaborators, previously documented the ability of intranasally administered nanoparticle-based influenza vaccines to induce both homologous and heterologous protection against IAV infection. The current project will further optimize the nanoparticle-based influenza vaccine designed for intranasal administration. Preliminary work demonstrated the ‘nanovaccine’ to be capable of inducing potent B cell and T cell immunity against the influenza A virus both in the upper and lower airway, as well as systemically. The induced airway immunity persists for extended periods in the form of resident memory T cells and germinal center B cells. Importantly, the vaccine design allows for protection against both homologous and heterologous influenza viruses, potentially minimizing the need for yearly immunization.

The research will be conducted in collaboration with Dr. Balaji Manicassamy in the Department of Microbiology and Immunology at the Carver College of Medicine and Dr. Balaji Narasimhan at Iowa State University.

Monday, February 13, 2023