Development of a hydrogen peroxide-inactivated vaccine that protects against viscerotropic yellow fever in a non-human primate model.

Yellow fever virus (YFV) is endemic in >40 countries and causes viscerotropic disease with up to 20%-60% mortality. Successful live-attenuated yellow fever (YF) vaccines were developed in the mid-1930s, but their use is restricted or formally contraindicated in vulnerable populations including infants, the elderly, and people with compromised immune systems. In these studies, we describe the development of a next-generation hydrogen peroxide-inactivated YF vaccine and determine immune correlates of protection based on log neutralizing index (LNI) and neutralizing titer-50% (NT ₅₀ ) studies. In addition, we compare neutralizing antibody responses and protective efficacy of hydrogen peroxide-inactivated YF vaccine candidates to live-attenuated YFV-17D (YF-VAX) in a rhesus macaque model of viscerotropic YF. Our results indicate that an optimized, inactivated YF vaccine elicits protective antibody responses that prevent viral dissemination and lethal infection in rhesus macaques and may be a suitable alternative for vaccinating vulnerable populations who are not eligible to receive replicating live-attenuated YF vaccines.
Competing Interests: Declaration of interests Oregon Health & Science University (OHSU), M.K.S., E.H., and I.J.A. have a financial interest in Najít Technologies, Inc., a company that may have a commercial interest in the results of this research and technology. This potential individual and institutional conflict of interest has been reviewed and managed by OHSU and Najít Technologies, Inc. M.S.D. is a consultant or member of a scientific advisory board for InBios, Ocugen, Vir Biotechnology, Topspin Therapeutics, and Moderna. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Emergent BioSolutions, Moderna, and Vir Biotechnology. I.J.A. and E.A.P. are inventors on US patent no. 10,744,198 entitled “Inorganic polyatomic oxyanions for protecting against antigenic damage during pathogen inactivation for vaccine production” and US patent nos. 11,141,475 and 11,633,470 entitled “Inactivating pathogens and producing highly immunogenic inactivated vaccines using a dual oxidation process.” M.K.S. and E.H. are inventors on US patent nos. 8,124,397 and 8,716,000 entitled “Inactivating pathogens with oxidizing agents for vaccine production.” No writing assistance was utilized in the production of this manuscript.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)