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

Abstract

<jats:title>Abstract</jats:title><jats:p>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.</jats:p>

SARS‐CoV‐2‐mediated immune system activation and potential application in immunotherapy

“…Among these epitopes, the CTL epitope VVNQNAQAL showed 100% identity with SARS‐CoV, with all others partly distinctive to SARS‐CoV‐2 13 . Interestingly, an effective CTL peptide (YQVNNLEEI) within the Ebola Zaire N protein may be implicated in SARS‐CoV‐2 vaccine design 29 …”

“Amantadine disrupts lysosomal gene expression; potential therapy for COVID19”

“…Furthermore CTSL polymorphisms could affect the susceptibility to SARS-CoV-2 where for example individuals with certain genetic variant have reduced expression of Cathepsin L and in turn could be protected or have lower viral titers. Additionally, elements of hosts MHC I and CTL mediated immune responses might affect viral proliferation 11 . There are susceptibility factors spanning from ethnicity background to age related groups, to comorbid conditions 12 .…”

Amantadine disrupts lysosomal gene expression: A hypothesis for COVID19 treatment

“…Furthermore CTSL polymorphisms could affect the susceptibility to SARS-CoV-2 where for example individuals with certain genetic variant have reduced expression of Cathepsin L and in turn could be protected or have lower viral titers. Additionally, elements of hosts major histocompatibility complex I (MHC I) and cytotoxic T cell lymphocytes (CTL) mediated immune responses might affect viral proliferation [11] . There are susceptibility factors spanning from ethnicity background to age related groups, to comorbid conditions [12] .…”