A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice

The spread of SARS-CoV-2 has caused a worldwide pandemic that has affected almost every aspect of human life. The development of an effective COVID-19 vaccine could limit the morbidity and mortality caused by infection and may enable the relaxation of social-distancing measures. Age is one of the most significant risk factors for poor health outcomes after SARS-CoV-2 infection; therefore, it is desirable that any new vaccine candidates elicit a robust immune response in older adults. Here, we use in-depth immunophenotyping to characterize the innate and adaptive immune response induced upon intramuscular administration of the adenoviral vectored ChAdOx1 nCoV-19 (AZD-1222) COVID-19 vaccine candidate in mice. A single vaccination generates spike-specific Th1 cells, Th1-like Foxp3+ regulatory T cells, polyfunctional spike-specific CD8+ T cells. and granzyme-B-producing CD8 effectors. Spike-specific IgG and IgM are generated from both the early extrafollicular antibody response and the T follicular helper cell-supported germinal center reaction, which is associated with the production of virus-neutralizing antibodies. A single dose of this vaccine generated a similar type of immune response in aged mice but of a reduced magnitude than in younger mice. We report that a second dose enhances the immune response to this vaccine in aged mice. This study shows that ChAdOx1 nCoV-19 induces both cellular and humoral immunity in adult and aged mice and suggests a prime-boost strategy is a rational approach to enhance immunogenicity in older persons. This study was supported by BBSRC, Lister institute of Preventative Medicine, EPSRC VaxHub, and Innovate UK. [Display omitted] ChAdOx1 nCoV-19 induces spike-specific polyfunctional CD8+ and CD4+ T cellsChAdOx1 nCoV-19 stimulates extrafollicular plasma cell and germinal center formationA single dose of ChAdOx1 nCoV-19 induces cellular and humoral immunity in aged miceA booster dose of ChAdOx1 nCoV-19 enhances immunogenicity in aged mice Effective COVID-19 vaccines will play a central role in the exit strategy from the worldwide pandemic. However, older persons often do not generate protective immunity upon vaccination due to age-dependent changes in their immune system. Because older people are more likely to have poor clinical outcomes after SARS-CoV-2 infection, vaccine strategies that elicit an optimal immune response in older bodies are urgently required. Researchers from the Babraham Institute , the Jenner Institute, an