2. Academic Validation
  3. 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

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

  • Vaccine. 2020 Jun 9;38(28):4464-4475. doi: 10.1016/j.vaccine.2020.04.034.
C V Herst 1,  S Burkholz 1,  J Sidney 2,  A Sette 2,  P E Harris 3,  S Massey 4,  T Brasel 4,  E Cunha-Neto 5,  D S Rosa 6,  W C H Chao 7,  R Carback 1,  T Hodge 1,  L Wang 1,  S Ciotlos 1,  P Lloyd 1,  R Rubsamen 8
Affiliations

Affiliations

  • 1 Flow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523, United States.
  • 2 La Jolla Institute for Allergy and Immunology, 9420 Athena Circle La Jolla, CA 92037, United States.
  • 3 Endocrinology Division, Department of Medicine, School of Medicine, Columbia University, New York, NY, USA.
  • 4 University of Texas, Medical Branch, 301 University Blvd, Galveston, TX 77555, United States.
  • 5 Laboratory of Clinical Immunology and Allergy-LIM60, University of São Paulo School of Medicine, São Paulo, Brazil; Institute for Investigation in Immunology (iii) INCT, São Paulo, Brazil; Heart Institute (Incor), School of Medicine, University of São Paulo, São Paulo, Brazil.
  • 6 Institute for Investigation in Immunology (iii) INCT, São Paulo, Brazil; Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil.
  • 7 University of Macau, E12 Avenida da Universidade, Taipa, Macau, China.
  • 8 Flow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523, United States; Massachusetts General Hospital, Department of Anesthesia, Critical Care and Pain Medicine, 55 Fruit St, Boston, MA 02114, United States. Electronic address: reidrubsamen@alum.mit.edu.
PMID: 32418793 DOI: 10.1016/j.vaccine.2020.04.034
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.

Keywords

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

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