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
Authors: Herst et al. Link to paper: https://www.biorxiv.org/content/10.1101/2020.02.25.963546v3
Journal/ Pre-Print: BioRxiv
Key Words: Ebola, CTL vaccine, COVID-19, controller
Research Highlights
1. A single vaccine comprising adjuvant (CpG) and peptide (NP44-52 (YQVNNLEEI)) in a microsphere protected mice from Ebola virus challenge
2. Conserved nucleocapsid proteins in SARS-CoV2 could be targeted by a cytotoxic CD8 lymphocyte (CTL)-based vaccine
Summary
This study probes the in vivo efficacy of a CTL-based vaccine incorporating the previously identified and conserved Ebola virus nucleocapsid protein sequence NP43-53 in a mouse model. NP43-53 however had no effect on induction of IFNg by splenocytes in vitro. Since this may be due to inefficient MHC binding and presentation, three shorter 9-mer sub-sequences were tested, with NP44-52 triggering the biggest IFNg response. A single vaccine containing 11µM microspheres with NP44-52, CpG adjuvant and a class II epitope from Ebola virus Zaire predicted to be important for efficient vaccination was administered I.P and protected mice from Ebola challenge. The authors hypothesise that a similar approach could be used for SARS-CoV2 and identify candidate 9-mers using in silico approaches.
Impact for SARS-CoV2/COVID19 research efforts
· Utilise methods and knowledge from developing an Ebola vaccine to develop a CTL-based vaccine for SARS-CoV2/COVID19 targeting conserved nucleocapsid protein sequences
Study Type
· Ex vivo splenocyte stimulation
· Pre-clinical in vivo vaccine study (C57BL/6 mice)
· In silico study probing predicted HLA binding affinities for SARS-CoV2 sequences
Strengths and limitations of the paper
Novelty: Ebola nucleocapsid peptide sequences previously identified and tested in vitro are shown here to form a protective vaccine in vivo. Similarly, conserved nucleocapsid sequences in SARS-CoV2 and predicted HLA-binding affinities are discussed.
Standing in the field: Authors have some previous publications in this area of research. Other vaccine approaches (e.g. targeting the spike proteins) are ongoing
Appropriate statistics: Statistical methodology unclear
Viral model used: Mice were challenged with Ebola virus M. musculus/COD/1976/Mayinga-CDC-808012. All SARS-CoV2 work in silico
Translatability: Suggested next step is to collect PBMCs from COVID-19 controllers and progressors to assess the presence of a differential response to candidate peptide sequences (e.g. IFNg induction by ELISPOT)
Main limitations:
· Early data showing superiority of NP44-52 (Fig 1A) not convincing
· Not consistent with conditions that are shown (e.g. comparing different peptide sequences) and route of vaccine administration
· Little discussion of the class II epitope from Ebola virus Zaire that was incorporated in the vaccine and the effects of this alone was not shown
· Difficult to follow in pre-print form e.g. acronyms not expanded, new data referred to only in discussion, no distinction between main and supplementary figures
· Extrapolation from mouse to man not clear