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.
Highlights
Development of safe and effective vaccines for some viruses such as human immunodeficiency virus (HIV) and EBOV has been challenging [19]
They reported that HIV controllers, individuals living with HIV not undergoing treatment who do not progress to AIDS, have CD8+ cells targeting different HLA restricted class I epitopes on HIV compared with progressors, individuals with HIV who progress to AIDS in the absence of therapy
Observations derived from individuals able to control HIV infection [43] and EBOV infection [50] demonstrating that control may be associated with specific CTL targeting behavior, suggest that there may be an important role for HLA-restricted peptide vaccines for protection against infectious disease for which development of an effective traditional whole protein vaccine has proved to be difficult
Summary
Development of safe and effective vaccines for some viruses such as HIV and EBOV has been challenging [19]. Human pathogen-derived peptide antigens that are recognized by C57BL/6 T-cells have been previously described These include peptides from vesicular stomatitis virus (VSV) RGYVYQGL [68], and human immunodeficiency virus (HIV) RGPGRAFVTI [5]. Wilson et al came to this conclusion based on studying splenocytes harvested from mice vaccinated with Ebola Zaire NP using a Venezuelan equine encephalitis (VEE) vector Their experiments showed that splenocytes from the vaccinated mice re-stimulated with NP43-53 had high levels of cytotoxic activity against target cells loaded with the EBOV 45 NP peptide. We set out to see if we could drive CTL expansion directed against NP43-53 to occur after vaccinating C57BL/6 mice with Ebola Zaire NP43-53 (VYQVNNLEEIC), 50 and to subsequently conduct an in-vivo EBOV challenge study to see if this peptide was protective. We set out to see if a similar approach to a CTL vaccine design for SARSCoV-2 would be feasible based on an analysis of the HLA binding characteristics of peptide sequences on SARS-CoV-2 nucleocapsid
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