Antibody-guided design of a human astrovirus vaccine

The National Institute of Allergy and Infectious Diseases awarded $919,605 to Scripps Research Institute on June 10, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to conduct antibody-guided vaccine development for human astrovirus.

The project will discover and characterize broadly neutralizing monoclonal antibodies against human astrovirus (HASTV) using next-generation antigen barcoding, single-cell multi-omics, and bioinformatics to screen HASTV-specific antibody repertoires from geographically distinct healthy adult and pediatric donor cohorts. The research aims to identify the structural and immunogenetic features of potently neutralizing antibodies, with the expectation of discovering thousands of novel anti-HASTV monoclonal antibodies. This work will accelerate the development of HASTV vaccines and therapeutics to address an estimated 4 million annual cases of HASTV infection in the United States, for which no clinically approved vaccines or therapeutics currently exist.

Work is performed at Scripps Research Institute in La Jolla, California. The period of performance runs from the award date through May 31, 2031. The award is classified as a Project Grant, the standard assistance type under the program.

Abstract

Viral diarrheal diseases cause substantial global morbidity and mortality. Diarrheal disease is the second leading cause of childhood mortality in the world, accounting for over 10% of all deaths of children under 5 years old. Gobally, over 1 billion cases of diarrheal diseases occur every year, making prevention of these diseases a public health concern of the highest priority. Human astrovirus (hastv) infection is a leading cause of viral diarrhea in children and has been shown to cause chronic gastrointestinal disease and fatal neurological disease in immunocompromised patients. There are nearly 4 million cases of hastv infection each year in the united states alone, and there are no clinically approved hastv-specific vaccines or therapeutics. Antibody-guided vaccine development leverages a deep understanding of productive antiviral antibody responses in order to design vaccine immunogens that deliberately focus the induced response toward highly conserved epitopes with the goal of reliably inducing broad, durable immunity. Using a cutting-edge monoclonal antibody (MAB) discovery approach based on next-generation antigen barcoding, single cell multi-omics, and sophisticated bioinformatics, we will exhaustively screen the hastv- specific antibody repertoires of geographically distinct donor cohorts to uncover the structural and immunogenetic features that differentiate broad and potently neutralizing hastv mabs. A more complete understanding of these exceptional - and potentially very rare - mabs will accelerate the development of hastv vaccines and therapeutics. We have assembled a collaborative, multidisciplinary group of investigators with a long history of productive collaboration and with highly complementary areas of expertise. We expect our work will result in the discovery of thousands of novel anti-hastv mabs from cohorts of healthy adult and pediatric participants. Detailed genetic, functional, and structural characterization of these mabs will reveal conserved sites of viral vulnerability, uncover the precise molecular mechanisms of viral neutralization, and inform our development of a broadly protective hastv vaccine.