Interaction Dynamics Between Innate and Adaptive Immune Cells Responding to SARS-CoV-2 Vaccination in Non-Human Primates

As new variants of SARS-CoV-2 continue to evolve and escape pre-existing immunity, testing updated vaccine antigens in non-human primates remains important for guiding clinical practice in humans. To date, such studies have focused on titers of binding and neutralizing antibodies, and frequencies of antigen-specific B and T cells. Here, we extend our understanding of the macaque immune response to vaccination with mRNA-1273 with an integrated approach that captures key interactions between the adaptive and innate immune responses. We show that a subset of S-specific T cells are characterized by the expression of key cytokines for activating innate immune responses, including CCL3, IL21, and IFNγ. We also observe an increase in CCR5-expressing intermediate monocytes and a shift of natural killer cells to a more mature cytotoxic phenotype. Antigen-specific B cells are polyclonal but demonstrate preferential usage of specific IGHV genes, and we observe two public clones, one of which matches a widely reported human anti-SARS-CoV-2 public B cell clone. The second vaccine dose elicits an increase in circulating germinal center-like B cells, which are more likely to be clonally expanded and target epitopes on the receptor binding domain. Both vaccine doses stimulate the expression of inflammatory response genes which have previously been associated with elevated antibody responses to a range of vaccines. Overall, this study provides a comprehensive picture of bidirectional signaling between innate and adaptive components of the immune system and suggests potential mechanisms for the enhanced response to a secondary exposure. Innate (monocyte, NK, or DC), CD4 memory T cells, or naïve B cells were sorted from 8 monkeys at baseline and/or 2 weeks after each dose of 100ug mRNA-1273. These cells were processed using the 10x Chromium for single cell sequencing. Antigen-specific memory B cells were also sorted from the post-vaccine time points into plates and sequenced using a SmartSeq-based protocol.