Immune history influences SARS-CoV-2 booster impacts: the role of efficacy and redundancy

Given the continued emergence of SARS-CoV-2 variants of concern as well as unprecedented vaccine development, it is crucial to understand the effect of the updated vaccine formulations at the population level. While bivalent formulations have higher efficacy in vaccine trials, translating these findings to real-world effectiveness is challenging due to the diversity in immune history, especially in settings with a high degree of natural immunity. Known socioeconomic disparities in key metrics such as vaccine coverage, social distancing, and access to healthcare have likely shaped the development and distribution of this immune landscape. Yet little has been done to investigate the impact of booster formulation in the context of host heterogeneity. Using two complementary mathematical models that capture host demographics and immune histories over time, we investigated the potential impacts of bivalent and monovalent boosters in low- and middle-income countries (LMICs). These models allowed us to test the role of natural immunity and cross-protection in determining the optimal booster strategy. Our results show that to avert deaths from a new variant in populations with high immune history, it is more important that a booster is implemented than which booster is implemented (bivalent vs. monovalent). However, in populations with low preexisting immunity, bivalent boosters can become optimal. These findings suggest that for many LMICs - where acquiring a new vaccine stock may be economically prohibitive - monovalent boosters can still be implemented as long as pre-existing immunity is high.