Abstract

Abstract Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines have shown extraordinary efficacy against SARS-CoV-2. Recently, we demonstrated that prime-boost coronavirus vaccine regimens can protect against heterologous coronaviruses (Dangi, The Journal of Clinical Investigation, 2021). However, it remains unclear whether boosters are required for such cross-protection. In this study, we show that booster immunizations are critical to elicit cross-protection against heterologous coronaviruses. We first vaccinated BALB/c mice intramuscularly with a poxvirus-based SARS-CoV-1 vaccine developed in 2004 (MVA-SARS-CoV-1) and compared cross-protection following an intranasal SARS-CoV-2 challenge, evaluating cross-protection after a prime-only regimen versus a prime-boost regimen. Interestingly, we show cross-protection only in mice that received boosters. We are currently testing the durability of cross-protection elicited by prime-boost vaccine regimens, and we are also extending these results to humans. Overall, our findings provide a rationale for universal coronavirus vaccines, and highlights the importance of boosters as a strategy to broaden cross-protection to other coronaviruses different than SARS-CoV-2. Supported by NIDA DP2 Avenir (1DP2DA051912-01) EREEP Grant Northwestern University

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