A LONG-INTERVAL VACCINE REGIMEN LEADS to STRONG HUMORAL RESPONSES AGAINST SARS-CoV-2

ABSTRACT

Background: While the standard regimen of the BNT162b2 mRNA vaccine includes two doses administered three weeks apart, some public health authorities decided to space them in a context of vaccine scarcity. This decision raised concerns about vaccine efficacy, notably against the many circulating variants. In this study, we analyzed the longitudinal humoral responses from before the first dose to 4 months after the second dose in a cohort of SARS-CoV-2 naïve and previously infected (PI) individuals, with an interval of sixteen weeks between the two doses. We compared these responses to those elicited in individuals receiving the three weeks dose interval. Methods: We measured the level of antibodies recognizing SARS-CoV-2 Spike or its receptor-binding domain, and the capacity of these antibodies to neutralize several variants of concern (VOCs) and other human coronaviruses. We also measured B cell responses and Fc-mediated effector functions (ADCC) elicited by vaccination. Results: We observed that in PI individuals, the first dose led to strong humoral responses that could not be significantly improved further upon administration of a second dose. In the naïve individual's group, the first dose induced weak neutralizing activity but strong Fc-mediated functions and the administration of the second dose 16 weeks after led to a significant increase of humoral responses, achieving similar levels to those measured in PI individuals. In both groups, we observed that plasmas were able to recognize and neutralize the Spike of different VOCs but also SARS-CoV-1. Conclusion: Our results show that individuals that received the extended BNT162b2 vaccine interval developed strong humoral responses. For the naïve donors, these responses were superior to those elicited by the three-week dose interval and comparable to the PI responses after one or two doses.