Rational design of a booster vaccine against COVID-19 based on antigenic distance.

Current COVID-19 vaccines are highly effective against symptomatic disease, but repeated booster doses using vaccines based on the ancestral strain offer limited additional protection against SARS-CoV-2 variants of concern (VOCs). To address this, we used antigenic distance to in silico select optimized booster vaccine seed strains effective against both current and future VOCs. Our model suggests that a SARS-CoV-1-based booster vaccine has the potential to cover a broader range of VOCs. Candidate vaccines including the spike protein from ancestral SARS-CoV-2, Delta, Omicron (BA.1), SARS-CoV-1, or MERS-CoV were experimentally evaluated in mice following two doses of the BNT162b2 vaccine. The SARS-CoV-1-based booster vaccine outperformed other candidates in terms of neutralizing antibody breadth and duration, as well as protective activity against Omicron (BA.2) challenge. This study suggests a unique strategy for selecting booster vaccines based on antigenic distance, which may be useful in designing future booster vaccines as new SARS-CoV-2 variants emerge.

Ecological dynamics of the gut microbiome in response to dietary fiber.

Dietary fibers are generally thought to benefit intestinal health. Their impacts on the composition and metabolic function of the gut microbiome, however, vary greatly across individuals. Previous research showed that each individual's response to fibers depends on their baseline gut microbiome, but the ecology driving microbiota remodeling during fiber intake remained unclear. Here, we studied the long-term dynamics of the gut microbiome and short-chain fatty acids (SCFAs) in isogenic mice with distinct microbiota baselines fed with the fermentable fiber inulin and resistant starch compared to the non-fermentable fiber cellulose. We found that inulin produced a generally rapid response followed by gradual stabilization to new equilibria, and those dynamics were baseline-dependent. We parameterized an ecology model from the time-series data, which revealed a group of bacteria whose growth significantly increased in response to inulin and whose baseline abundance and interspecies competition explained the baseline dependence of microbiome density and community composition dynamics. Fecal levels of SCFAs, such as propionate, were associated with the abundance of inulin responders, yet inter-individual variation of gut microbiome impeded the prediction of SCFAs by machine learning models. We showed that our methods and major findings were generalizable to dietary resistant starch. Finally, we analyzed time-series data of synthetic and natural human gut microbiome in response to dietary fiber and validated the inferred interspecies interactions in vitro. This study emphasizes the importance of ecological modeling to understand microbiome responses to dietary changes and the need for personalized interventions.