In this Perspective, Marc Lipsitch and Natalie Dean consider what would happen if a COVID-19 vaccine offers little to no protection in high-risk groups, like the elderly and those with comorbidities, yet is able to reduce infection or infectiousness in younger adults. In such a case, they say, an indirect protection strategy - whereby those in contact with high-risk individuals are vaccinated to reduce transmission -could be preferred once vaccine supplies become large enough. This consideration mirrors the way influenza vaccine campaigns initially targeted the elderly, in an effort at direct protection, but more recently have focused on the general population, in part to enhance indirect protection. Measuring indirect effects of vaccines is harder than detecting direct effects, the authors note. "It is urgent, therefore, to obtain evidence on how each candidate vaccine affects infectiousness either before approval or soon after, when scarcity may justify randomized distribution of a vaccine," they say. "[H]aving reliable evidence on direct and indirect protection can help plan how to use these vaccines in a coordinated way." The evidence needed will depend in large part on results from Phase 3 trials; though, even after the trials are done, say the authors, questions that will require follow-up will remain, including about whether approved vaccines can prevent infection or reduce contagiousness, and also subgroup-specific efficacy. They point out that the clearest evidence of indirect protection from a vaccine is from a vaccine that prevents infection entirely, thereby reducing transmission. Ideally, write Lipsitch and Dean, the phase 3 trials in progress will identify more than one safe, effective vaccine for regulatory approval and deployment. Post-approval vaccine studies will then take on an important role for continued assessment of vaccine effectiveness, the authors say. In doing these, researchers can leverage ongoing surveillance, the authors say; these programs can simultaneously monitor more than one vaccine, enabling assessment of their relative merits.