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

Publication date: Jan 20, 2024

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.

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Concepts Keywords
Driving Diversity Outbred
Environmental host genetic diversity
Host SARS-CoV-2
Mice vaccination
Vaccines

Semantics

Type Source Name
disease IDO host
disease VO vaccination
disease VO population
disease MESH COVID-19 pandemic
disease VO effective
disease VO vaccine efficacy
disease VO vaccine
disease MESH influenza
disease MESH tuberculosis
pathway KEGG Tuberculosis
disease VO immunized
disease VO vaccinated
disease VO titer
disease VO USA
drug DRUGBANK Coenzyme M
disease MESH measles
pathway KEGG Measles
disease MESH mumps
disease MESH rubella
disease MESH hepatitis
disease IDO susceptibility
disease IDO pathogen
disease MESH infection
disease VO subunit vaccine
disease MESH weight loss
disease VO immunization
drug DRUGBANK Water
disease IDO blood
disease VO volume
disease VO URE
disease MESH breakthrough infection
disease IDO assay
disease VO frequency
disease IDO replication
disease VO unvaccinated
pathway KEGG Viral replication
drug DRUGBANK Spinosad
disease VO boost vaccination
disease MESH morbidity
disease IDO immune response

Original Article

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