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Publications

Journal Article Epublish 4 citations

PubMed: 38276675 DOI: 10.3390/vaccines12010103

Host Genetic Variation Impacts SARS-CoV-2 Vaccination Response in the Diversity Outbred Mouse Population.

Vaccines (Basel) 12(1)

Authors: Marta C Cruz Cisneros, Elizabeth J Anderson, Brea K Hampton, BreantiƩ Parotti, Sanjay Sarkar, Sharon Taft-Benz, Timothy A Bell, Matthew Blanchard, Jacob A Dillard, Kenneth H Dinnon, Pablo Hock, Sarah R Leist, Emily A Madden, Ginger D Shaw, Ande West, Ralph S Baric, Victoria K Baxter, Fernando Pardo-Manuel de Villena, Mark T Heise, Martin T Ferris

Affiliations

  • Genetics and Molecular Biology Curriculum, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Department of Genetics, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Division of Comparative Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
  • Texas Biomedical Research Institute, San Antonio, TX 78227, USA.
  • Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.

Abstract

The COVID-19 pandemic led to the rapid and worldwide development of highly effective vaccines against SARS-CoV-2. However, there is significant individual-to-individual variation in vaccine efficacy due to factors including viral variants, host age, immune status, environmental and host genetic factors. Understanding those determinants driving this variation may inform the development of more broadly protective vaccine strategies. While host genetic factors are known to impact vaccine efficacy for respiratory pathogens such as influenza and tuberculosis, the impact of host genetic variation on vaccine efficacy against COVID-19 is not well understood. To model the impact of host genetic variation on SARS-CoV-2 vaccine efficacy, while controlling for the impact of non-genetic factors, we used the Diversity Outbred (DO) mouse model. We found that DO mice immunized against SARS-CoV-2 exhibited high levels of variation in vaccine-induced neutralizing antibody responses. While the majority of the vaccinated mice were protected from virus-induced disease, similar to human populations, we observed vaccine breakthrough in a subset of mice. Importantly, we found that this variation in neutralizing antibody, virus-induced disease, and viral titer is heritable, indicating that the DO serves as a useful model system for studying the contribution of genetic variation of both vaccines and disease outcomes.

MeSH

Genetic Variation, Sars-Cov-2, Vaccines, Antibodies, Neutralizing, Vaccination, Viruses, Severe Acute Respiratory Syndrome-Related Coronavirus, Vaccine Efficacy

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