Cytokine profile of anti-spike CD4+T cells predicts humoral and CD8+T cell responses after anti-SARS-CoV-2 mRNA vaccination

Abstract Coordinating immune responses – humoral and cellular – is vital for protection against severe Covid-19. Our study evaluates a multicytokine CD4+T cell signature’s predictive potential for post-vaccinal serological and CD8+T cell responses. A cytokine signature composed of four cytokines (IL-2, TNF-α, IP10, IL-9) excluding IFN-g and generated through machine learning, effectively predicted the CD8+T cell response following mRNA-1273 or BNT162b2 vaccine administration. Its applicability extends to murine vaccination models, encompassing diverse immunization routes (such as intranasal) and vaccine platforms (including adjuvanted proteins). Notably, we found correlation between CD4+T lymphocyte-produced IL-21 and the humoral response. Consequently, we propose a straightforward test that offers a rapid overview and deepens our understanding of complex immune responses. This approach holds particular relevance for scenarios involving immunocompromised patients or pandemics. This study also underscores the pivotal role of CD4+T cells during a vaccine response, presenting an opportunity harnessing this role in vaccine immunomonitoring.