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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

CV Herst, S Burkholz, J Sidney, A Sette, PE Harris, S Massey, T Brasel, E Cunha-Neto, DS Rosa, WCH Chao, R Carback, T Hodge, L Wang, S Ciotlos, P Lloyd, R Rubsamen
doi: https://doi.org/10.1101/2020.02.25.963546
CV Herst
aFlow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523
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S Burkholz
aFlow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523
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J Sidney
iLa Jolla Institute for Allergy and Immunology, 9420 Athena Circle La Jolla, CA 92037
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A Sette
iLa Jolla Institute for Allergy and Immunology, 9420 Athena Circle La Jolla, CA 92037
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PE Harris
gEndocrinology Division, Department of Medicine, School of Medicine, Columbia University, New York, New York, USA
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S Massey
bUniversity of Texas, Medical Branch, 301 University Blvd, Galveston, TX 77555
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T Brasel
bUniversity of Texas, Medical Branch, 301 University Blvd, Galveston, TX 77555
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E Cunha-Neto
cLaboratory of Clinical Immunology and Allergy-LIM60, University of São Paulo School of Medicine, São Paulo, Brazil
dInstitute for Investigation in Immunology (iii) INCT, São Paulo, Brazil
eHeart Institute (Incor), School of Medicine, University of São Paulo, São Paulo, Brazil
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DS Rosa
dInstitute for Investigation in Immunology (iii) INCT, São Paulo, Brazil
fDepartment of Microbiology, Immunology and Parasitology, Federal University of São Paulo (UNIFESP/EPM), São Paulo, Brazil
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WCH Chao
jUniversity of Macau, E12 Avenida da Universidade, Taipa, Macau, China
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R Carback
aFlow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523
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T Hodge
aFlow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523
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L Wang
aFlow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523
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S Ciotlos
aFlow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523
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P Lloyd
aFlow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523
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R Rubsamen
aFlow Pharma, Inc., 3451 Vincent Road, Pleasant Hill, CA 94523
hMassachusetts General Hospital, Department of Anesthesia, Critical Care and Pain Medicine, 55 Fruit St, Boston, MA 02114
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  • For correspondence: reidrubsamen@alum.mit.edu
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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 COVID-19 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.

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  • Additional citations and moved some figures and tables to supplementary materials.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted March 09, 2020.
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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
CV Herst, S Burkholz, J Sidney, A Sette, PE Harris, S Massey, T Brasel, E Cunha-Neto, DS Rosa, WCH Chao, R Carback, T Hodge, L Wang, S Ciotlos, P Lloyd, R Rubsamen
bioRxiv 2020.02.25.963546; doi: https://doi.org/10.1101/2020.02.25.963546
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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
CV Herst, S Burkholz, J Sidney, A Sette, PE Harris, S Massey, T Brasel, E Cunha-Neto, DS Rosa, WCH Chao, R Carback, T Hodge, L Wang, S Ciotlos, P Lloyd, R Rubsamen
bioRxiv 2020.02.25.963546; doi: https://doi.org/10.1101/2020.02.25.963546

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