Development of New and More Effective Live-Attenuated Influenza Vaccines
Abstract
Topic Area: The proposed project relates to the Fiscal Year 2017 (FY17) Peer Reviewed Medical Research Program (PRMRP) Topic Area of “Influenza.” More narrowly, it addresses the FY17 PRMRP Area of Encouragement “Development and evaluation of novel, innovative, and/or combination influenza therapies.” Recently (2012), and to improve the efficacy of the seasonal influenza vaccine, quadrivalent influenza inactivated vaccine (IIV) and live-attenuated influenza vaccine (LAIV) formulations that include both influenza B virus (IBV) lineages components (Victoria-like and Yamagata-line lineages) were approved by the Food and Drug Administration (FDA) to substitute the previously trivalent formulations. However, since its introduction during the 2013-2014 influenza season, different studies revealed low effectiveness of the quadrivalent LAIV, mainly to the H1N1 influenza A virus (IAV) component in the vaccine. Based on this low vaccine effectiveness, the Advisory Committee on Immunization Practices (ACIP) recommends that the LAIV should not be used for the 2016-2017 influenza season. To date, the cause of reduced vaccine effectiveness of the quadrivalent LAIV is not known, and new approaches to improve the efficacy of the currently human LAIV are urgently needed. The overall goal of this application is to test, for the first time, the novel hypothesis that altering the ability of influenza NS1 and/or PA-X proteins to inhibit host protein expression, and thus suppression of innate and adaptive immune responses, can be used to improve the immunogenicity and protection efficacy, without affecting its safety and stability profile, of the human LAIV to develop more effective LAIV to combat disease caused by this important human respiratory pathogen.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810460
Entities
People
- Luis Martinez-Sobrido
Organizations
- United States Army
- University of Rochester