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Understanding COVID-19 vaccine efficacy

The elderly and people with comorbidities are at greatest risk of severe coronavirus disease 2019 (COVID-19). A safe and effective vaccine could help to protect these groups in two distinct ways: direct protection, where high-risk groups are vaccinated to prevent disease, and indirect protection, where those in contact with high-risk individuals are vaccinated to reduce transmission. 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. Because influenza vaccines induce weaker, shorter-lived immune responses in the elderly than in young adults, increasing indirect protection may be a more effective strategy. It is unknown whether the same is true for COVID-19 vaccines.

For COVID-19, age-structured mathematical models with realistic contact patterns are being used to explore different vaccination plans (1, 2), with the recognition that vaccine doses may be limited at first and so should be deployed strategically. But as supplies grow large enough to contemplate an indirect protection strategy, the recommendations of these models depend on the details of how, and how well, these vaccines work and in which groups of people. How can the evidence needed to inform strategic decisions be generated for COVID-19 vaccines?

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