Fig. 3: The proposed converging impact of differences in the microbial community and circulating metabolic composition on the generation of normal and dysfunctional SARS-CoV-2 vaccine responses.
Environmental factors can lead to alterations in the microbiome and metabolite composition, which are sensed by the innate immune system. This can lead to impaired innate immune function, disrupted antigen presentation and improper skewing of adaptive (T cell and B cell) responses. In this environment of dysregulated adaptive immune activation, antigen-specific responses induced during vaccination are functionally altered compared to those generated under homeostatic conditions. This can not only impact generating a protective vaccine response but also directly modulates the induction of memory responses, which substantially dictates the longevity of vaccine-induced immunity. In this way, differences in the combination of environmental factors between individuals can substantially impact on both the primary generation of a vaccine response and how long an individual is protected from future infection. AA, amino acid; Teff cells, effector T cells; TFH cells, follicular helper T cells; TM cells, memory T cells; GC, germinal center.
