Immunogenicity and protective efficacy of a rhesus adenoviral vaccine targeting conserved COVID-19 replication transcription complex

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  • Dagotto, Gabriel
    • Other Affiliation: Harvard Medical School
  • Ventura, John D.
    • Other Affiliation: Harvard Medical School
  • Martinez, David R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Anioke, Tochi
    • Other Affiliation: Harvard Medical School
  • Chung, Benjamin S.
    • Other Affiliation: Harvard Medical School
  • Siamatu, Mazuba
    • Other Affiliation: Harvard Medical School
  • Barrett, Julia
    • Other Affiliation: Harvard Medical School
  • Miller, Jessica
    • Other Affiliation: Harvard Medical School
  • Schäfer, Alexandra
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Yu, Jingyou
    • Other Affiliation: Harvard Medical School
  • Tostanoski, Lisa H.
    • Other Affiliation: Harvard Medical School
  • Wagh, Kshitij
    • Other Affiliation: Los Alamos National Laboratory
  • Baric, Ralph S.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Korber, Bette
    • Other Affiliation: Los Alamos National Laboratory
  • Barouch, Dan H.
    • Other Affiliation: Harvard Medical School
Abstract
  • The COVID-19 pandemic marks the third coronavirus pandemic this century (SARS-CoV-1, MERS, SARS-CoV-2), emphasizing the need to identify and evaluate conserved immunogens for a pan-sarbecovirus vaccine. Here we investigate the potential utility of a T-cell vaccine strategy targeting conserved regions of the sarbecovirus proteome. We identified the most conserved regions of the sarbecovirus proteome as portions of the RNA-dependent RNA polymerase (RdRp) and Helicase proteins, both of which are part of the coronavirus replication transcription complex (RTC). Fitness constraints suggest that as SARS-CoV-2 continues to evolve these regions may better preserve cross-reactive potential of T-cell responses than Spike, Nucleocapsid, or Membrane proteins. We sought to determine if vaccine-elicited T-cell responses to the highly conserved regions of the RTC would reduce viral loads following challenge with SARS-CoV-2 in mice using a rhesus adenovirus serotype 52 (RhAd52) vector. The RhAd52.CoV.Consv vaccine generated robust cellular immunity in mice and led to significant reductions in viral loads in the nasal turbinates following challenge with a mouse-adapted SARS-CoV-2. These data suggest the potential utility of T-cell targeting of conserved regions for a pan-sarbecovirus vaccine.
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Resource type
  • Article
License
  • Attribution 4.0 International
Journal title
  • NPJ vaccines
Journal volume
  • 7
Journal issue
  • 1
Language
  • English
Version
  • Publisher
Funder
  • National Institute of Health (CA260476, Al158571)
  • Ragon Institute of MGH, MIT, and Harvard
  • Musk Foundation
  • Los Alamos National Laboratory LDRD Exploratory Research 20220399ER
  • Burroughs Welcome Fund Postdoctoral Enrichment Program Award
  • Hanna H. Gray Fellowship from the Howard Hugues Medical Institute
ISSN
  • 2059-0105

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