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.

Autor: Herst CV; Flow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523, United States., Burkholz S; Flow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523, United States., Sidney J; La Jolla Institute for Allergy and Immunology, 9420 Athena Circle La Jolla, CA 92037, United States., Sette A; La Jolla Institute for Allergy and Immunology, 9420 Athena Circle La Jolla, CA 92037, United States., Harris PE; Endocrinology Division, Department of Medicine, School of Medicine, Columbia University, New York, NY, USA., Massey S; University of Texas, Medical Branch, 301 University Blvd, Galveston, TX 77555, United States., Brasel T; University of Texas, Medical Branch, 301 University Blvd, Galveston, TX 77555, United States., Cunha-Neto E; 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., Rosa DS; 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., Chao WCH; University of Macau, E12 Avenida da Universidade, Taipa, Macau, China., Carback R; Flow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523, United States., Hodge T; Flow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523, United States., Wang L; Flow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523, United States., Ciotlos S; Flow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523, United States., Lloyd P; Flow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523, United States., Rubsamen R; 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.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2020 Jun 09; Vol. 38 (28), pp. 4464-4475. Date of Electronic Publication: 2020 Apr 28.
DOI: 10.1016/j.vaccine.2020.04.034
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest CV Herst, Scott Burkholz, Lu Wang, Peter Lloyd and Reid Rubsamen are employees of Flow Pharma, Inc. all receiving cash and stock compensation. Alessandro Sette, Paul Harris, William Chao and Tom Hodge are members of Flow Pharma's Scientific Advisory Board. Alessandro Sette has received cash and stock compensation as an SAB member. Richard Carback and Serban Ciotlos are consultants to Flow Pharma, both receiving cash and stock compensation. John Sidney works with Alessandro Sette at the La Jolla Institute of Allergy and Immunology. Flow Pharma, Inc. has previously contracted with the La Jolla Institute of Allergy and Immunology to support other research not related to this study funded under STTR contract CBD18-A-002-0016. Reid Rubsamen, CV Herst, Scott Burkholz, Lu Wang, Peter Lloyd, Richard Carback, Serban Ciotlos and Tom Hodge are named inventors on various issued and pending patents relating to Flow Pharma’s technology. All of the rights to all of these patents have been assigned by each of the inventors to Flow Pharma. Shane Massey, Trevor Brasel, Edecio Cunha-Neto and Daniela Rosa have nothing to declare.
(Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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