An effective CTL peptide vaccine for Ebola Zaire Based on Survivors’ CD8+ targeting of a particular nucleocapsid protein epitope with potential implications for COVID-19 vaccine design
C.v. Herst, Scott Burkholz, John Sidney, Alessandro Sette, Paul E. Harris, Shane Massey, Trevor Brasel, Edécio Cunha‐Neto, Daniela Santoro Rosa, William Chong Hang Chao, Richard T. Carback, Tom Hodge, L. Wang, Serban Ciotlos, Peter Lloyd, Reid Rubsamen
Abstract
The 2013-2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP). It has been suggested that epitopes on the EBOV NP could form an important part of an effective T-cell vaccine for Ebola Zaire. We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse adapted EBOV challenge. A single vaccination in a C57BL/6 mouse using an adjuvanted microsphere peptide vaccine formulation containing NP44-52 is enough to confer immunity in mice. Our work suggests that a peptide vaccine based on CD8+ T-cell immunity in EBOV survivors is conceptually sound and feasible. Nucleocapsid proteins within SARS-CoV-2 contain multiple Class I epitopes with predicted HLA restrictions consistent with broad population coverage. A similar approach to a CTL vaccine design may be possible for that virus.