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, S. Burkholz, J. Sidney, A. Sette, P. E. Harris, S. Massey, T. Brasel, E. Cunha-Neto, D. S. Rosa, W. C.H. Chao, R. Carback, T. Hodge, L. Wang, S. Ciotlos, P. Lloyd, R. Rubsamen

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4464-4475
Number of pages12
JournalVaccine
Volume38
Issue number28
DOIs
StatePublished - Jun 9 2020

Keywords

  • Controller
  • COVID-19
  • CTL Vaccine
  • Ebola Zaire vaccine
  • Flow Focusing
  • SARS-CoV-2
  • YQVNNLEEI

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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