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

• Published in: Vaccine Vol. 38; no. 28; pp. 4464 - 4475
• Main Authors: Herst, C.V., Burkholz, S., Sidney, J., Sette, A., Harris, P.E., Massey, S., Brasel, T., Cunha-Neto, E., Rosa, D.S., Chao, W.C.H., Carback, R., Hodge, T., Wang, L., Ciotlos, S., Lloyd, P., Rubsamen, R.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 09.06.2020; Elsevier Limited; The Author(s). Published by Elsevier Ltd
• Subjects: Acquired immune deficiency syndrome; AIDS; Allergy and Immunology; Amino Acid Sequence; Amino acids; Animals; Antigen presentation; CD8 antigen; CD8-positive T-lymphocytes; Controller; Coronavirus infections; Coronavirus Infections - immunology; Coronavirus Infections - prevention & control; COVID-19; COVID-19 Vaccines; CTL Vaccine; Cytotoxicity; Democratic Republic of the Congo; Design; Disease Models, Animal; Drug Design; Ebola Vaccines - chemistry; Ebola Vaccines - immunology; Ebola virus; Ebola Zaire vaccine; Ebolavirus; Epitopes; Epitopes, T-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - immunology; Flow Focusing; Hemorrhagic Fever, Ebola - immunology; Hemorrhagic Fever, Ebola - prevention & control; Histocompatibility antigen HLA; HIV; Human immunodeficiency virus; Humans; Immunity; Ligands; Lymphocytes T; Mice; Mice, Inbred C57BL; microparticles; Morbidity; mortality; nucleocapsid proteins; Nucleocapsid Proteins - chemistry; Nucleocapsid Proteins - immunology; Nucleocapsids; Pandemics - prevention & control; Peptides; Pneumonia, Viral - immunology; Pneumonia, Viral - prevention & control; Proteins; Public health; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Survival; T-Lymphocytes, Cytotoxic - immunology; Vaccination; vaccine development; Vaccines; Vaccines, Subunit - chemistry; Vaccines, Subunit - immunology; Viral diseases; Viral Vaccines - chemistry; Viral Vaccines - immunology; Viruses; Western Africa; YQVNNLEEI; Zaire; West Africa; Western Africa; Democratic Republic of the Congo; COVID-19; Flow Focusing; Ebola Zaire vaccine; YQVNNLEEI; SARS-CoV-2; CTL Vaccine; Controller
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2020.04.034

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.