Imperfect future immunity: Humans are infected by several seasonal and cross-reacting coronaviruses. None provokes fully protective immunity, and repeat infections are the norm. Vaccines tend to be less efficient than natural infections at provoking immunity, and there are risks of adverse cross-reactions. Saad-Royet al.used a series of simple models for a variety of immune scenarios to envisage immunological futures for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with and without vaccines. The model outcomes show that our imperfect knowledge about the imperfect coronavirus immune landscape can give rise to diverging scenarios ranging from recurring severe epidemics to elimination. It is critical that we accurately characterize immune responses to SARS-CoV-2 for translation into managing disease control.Science, this issue p.811

One dose or two?: For two-dose vaccines against severe acute respiratory syndrome coronavirus 2, some jurisdictions have decided to delay the second dose to rapidly get the vaccine into more people. The consequences of deviating from manufacturer-prescribed dosing regimens are unknown but will depend on the strength of immune responses to the vaccines. Saad-Roy et al. took a modeling approach to tackling the inevitable uncertainties facing vaccine rollout. The authors found that although one-dose strategies generally reduce infections in the short term, in the long term, the outcome depends on immune robustness. A one-dose strategy may increase the potential for antigenic evolution if immune responses are suboptimal and the virus continues to replicate in some vaccinated people, potentially leading to immune-escape mutations. It is critical to gather serological data from vaccinated people and, to avoid negative outcomes, to ramp up vaccination efforts worldwide. Science , this issue p. 363

Stockpiling and control: A triumph that has emerged from the catastrophe of the severe acute respiratory syndrome coronavirus 2 pandemic has been the rapid development of several potent vaccines. However, 18 months into the pandemic and more than 6 months after vaccine approval, wealthy countries remain the major beneficiaries. Wagner et al . model the consequences of vaccine stockpiling in affluent countries on disease rates in lower- and middle-income countries and the consequences for the eruption of new variants that could jeopardize the early success of vaccines. For countries that can readily access vaccines, it would be better to share vaccines equitably to lower disease burdens in countries with less access, reduce the cost of having to be constantly vigilant for case imports, and minimize virus evolution. —CA

Despite the rapid development of safe and highly effective vaccines against coronavirus disease 2019 (COVID-19), the strategy for their distribution has been and remains contentious. Mathematical models can be used to guide and inform these strategies; however, uncertainties in critical immunological and evolutionary parameters of SARS-CoV-2 can limit the predictive power of models. Notwithstanding these ongoing uncertainties, we discuss how models have been applied to guide health policy decisions related to vaccination against COVID-19, and how they may be applied in the future in the context of booster doses under different scenarios related to disease-specific factors and global distribution. Mathematical models have been used to guide strategies for COVID-19 vaccine distribution. But with the emergence of new SARS-CoV-2 variants and waning immunity, how should vaccine distribution be prioritized?