Design and testing picornavirus vaccine candidates

PROJECT SUMMARY – RP1
Design and testing of picornavirus vaccine candidates
The need for effective vaccines against enteroviruses and rhinoviruses cannot be overstated. Given the ever-
increasing threat of these viral infections and their associated health impacts, it is crucial to develop a general
platform for rapid vaccine development. With this medical need in mind, here we propose to create such a
platform, one that can be easily and quickly adapted to different strains of the viruses as they emerge. We
envision a system that combines the latest tools and technologies, including new developments in molecular
biology, immunology, and vaccine design, to accelerate the discovery and development of new candidate
vaccines. By doing so, we mill make meaningful contributions towards protecting global populations from the
devastating effects of these viruses.
Our general approach is to design immunogens that will provide effective protection against these viruses,
incorporating information about sites of vulnerability for protective human monoclonal antibodies (mAbs)
(discovered in Research Project 2, focused on human mAbs). This effort is a crucial undertaking, as the five
human pathogens prototypes on which we will focus - Rhinovirus C, Enteroviruses A71 and D68, Coxsackievirus
B3 and Echovirus 11, are among the most medically significant viruses causing respiratory, gastrointestinal, and
nervous system diseases on a global scale. The innovative candidate vaccine platforms we will deploy are
designed with multiple technical advances, especially structurally-stabilized virus-like particles (VLPs) that
can be used as protein- or nucleic-acid-based immunogens. By leveraging the knowledge the BP4 consortium
obtains from detailed structure-function studies of protective human monoclonal antibodies, we can develop new
candidate vaccines that induce protection from pathogenic picornaviruses and reduce the risk of dangerous
outbreaks. In addition, we will combine these immunogens with a self-replicative RNA-based mucosal adjuvant.
This novel adjuvant mimics the effects of virus infection and triggers innate local immune responses, ensuring
robust T-cell and B-cell adaptive immune responses and long-lasting protection. By generating both systemic
and mucosal immune responses, we aim to create a robust defense against these viruses.
In the context of these studies, we will also develop new animal models to optimize testing of novel vaccination
strategies and to examine the immunogenicity and protection elicited by our candidate vaccines. The lead
vaccines will be advanced with an extensive network of industry and non-profit partners.

Grant Number: 1U19AI181979-01
NIH Institute/Center: NIH
Principal Investigator: Raul Andino