Universal Influenza Vaccines (UIV)

National Institute Of Allergy And Infectious Diseases

Investigators

Abstract

During FY24/25 LV has been working on different aspects of highly pathogenic avian influenza viruses (HPAIV) H5N1. The Sections headed by Vincent Munster and Emmie de Wit have been instrumental in obtaining different HPAIV H5N1 isolates from different avian and mammalian species. A biobank was created by growing virus stocks and characterizing those stocks in vitro including sequence determination. This is an invaluable resource for LV, DIR and NIAID in future years. Important public health questions associated with the emergence of H5N1 in cattle have been addressed immediately by the groups of Drs. Emmie de Wit and Vincent Munster. Inactivation of H5N1 in raw milk at different temperatures was studied. It was determined that pasteurization is likely sufficient to large reduce exposure through consumption of milk (Kaiser et al. N Engl J Med 2024). A rapid detection assay for H5N1 in milk was developed and evaluated for future use in experimental and surveillance settings (Ochwoto et al. Pathogens 2025). Stability testing of H5N1 was tested next demonstrating stability of infectious H5N1 virus in irradiated raw milk and wastewater and on surfaces. We found a relatively slow decay in milk, indicating that contaminated milk and fomites pose transmission risks (Kaiser et al. Emerg Infect Dis 2025). These studies were instrumental for forming important animal and public health guidelines. First in vitro replication and host response data were generated in the group of Dr. de Wit using human lung organoids. The study suggested that the contemporary H5N1 virus circulating in cattle likely exhibits reduced human disease severity compared to a historical H5N1 isolate from 2004 (Flagg et al. Emerg Infect Dis 2025). Small H5N1 animal disease model development started with mice. The groups of Drs. de Wit, Munster and Feldmann showed that a contemporary H5N1 bovine isolate is highly virulent for mice rapidly causing acute pulmonary and neurologic disease (Tipih et al. Nat Commun 2025). Furthermore, enhanced neurotropism was associated with the bovine H5N1 isolate in C57BL/6J mice compared to a historical H5N1 isolate (Goldin et al. NPJ Viruses 2025). Balb/C and C57BL/6J mice serve as severe disease model for the contemporary H5N1 isolates. The mouse model was utilized to demonstrate the efficacy of a replicating RNA vaccine based on a contemporary H5N1 hemagglutinin (HA) sequence confers rapid protection against H5N1 virus challenge (Hawman et al. Nat Commun 2025). In addition, we investigated routes of infection with bovine HPAIV H5N1 in cynomolgus macaques. We showed that intranasal or intratracheal inoculation of macaques could cause systemic infection resulting in mild and severe respiratory disease, respectively. By contrast, infection by the orogastric route resulted in limited infection and seroconversion of macaques that remained subclinical. This established the cynomolgus macaque as a H5N1 surrogate model for human disease (Rosenke et al. Nature 2025). We utilized the nonhuman primate model to further evaluated the protective capacity of our replicating RNA vaccine expressing the contemporary H5N1 HA or a historical H5 HA. We found that both vaccines conferred robust protection against lethal H5N1 challenge, protecting against clinical disease and death, reducing viral loads and signs of respiratory illness (Hawman et al. Sc Transl Med, in revision).