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

Silva-Cayetano, Alyssa; Foster, William S.; Innocentin, Silvia; Belij-Rammerstorfer, Sandra; Spencer, Alexandra J.; Burton, Oliver T.; Fra-Bidó, Sigrid; Le Lee, Jia; Thakur, Nazia; Conceicao, Carina; Wright, Daniel; Barett, Jordan; Evans-Bailey, Nicola; Noble, Carly; Bailey, Dalan; Liston, Adrian; Gilbert, Sarah C.; Lambe, Teresa; Linterman, Michelle A.

Background The spread of SARS-CoV-2 has caused a global 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. Methods 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. Findings 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 centre reaction, which is associated with the production of virus neutralising 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. Conclusions 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. Funding BBSRC, Lister institute of Preventative Medicine, EPSRC VaxHub and Innovate UK