Substudy: Understanding COVID-19 vaccine responses in the setting of immunotherapy

Since its emergence, SARS-Cov2 has rapidly and widely spread across the globe due to lack of prior protective immunity in the human species. With widespread mitigation measures, all efforts focused on generating effective vaccination strategies that will provide herd immunity and protect the most vulnerable populations. However, there is very little known on how the immune response evolves following vaccination against SARS-Cov2 in the setting of immunotherapy. Immunotherapy that blocks the inhibitory receptor Programmed Cell Death -1 (PD-1) is first-line therapy for unresectable or metastatic melanoma. Anti-PD-1 antibody infusion is now increasingly being tested for other cancers as well, with relatively recent FDA-approval for use in metastatic non-small cell lung cancer, renal cell carcinoma, and metastatic or recurrent head and neck squamous cell carcinoma. This study is designed to better understand antibody responses in the setting of PD-1 blockade compared to other anti-cancer therapies in melanoma patients. Identification of impaired vaccine responses would have major implications for vaccination in the setting of immunotherapy and will also elucidate the role of PD-1 signaling in generating an effective antibody-mediated immune response. Available published data from vaccine trials indicate immunogenicity and serological immunity, but key questions remain about the nature of the cellular immune response underlying antibody responses. CD4 T cells, and in particular follicular helper CD4 T cells (Tfh) are required to make an optimal B cell response by providing help to B cells, helping to form a germinal center and fostering formation of high-quality antibody. Responses of Tfh and B cells can be identified in peripheral blood following administration of other vaccines, but whether different SARS-Cov2 vaccines induce Tfh and how these Tfh responses relate to B cell responses, induction of antibody and durability of cellular and humoral immunity over time is unclear. Understanding the nature of these T cell and B cell responses to the SARS-Cov2 vaccines is of paramount importance to gain a deeper knowledge of immunity to COVID-19 and to improve vaccination strategies in the future.