Delaying Second Vaccine Dose Could Reduce Numbers in the Near Term

Delaying doses of COVID-19 vaccines will reduce case numbers in the short term. However, the long-term case burden and the potential for evolution of viral escape from immunity will depend on the robustness of immune responses generated by natural infections. Researchers from Princeton University and McGill University published a study in the journal Science. Several countries are delaying a second COVID-19 vaccine dose to address supply shortages and rapidly increase the number of people immunized.

The researchers used a simple model to project forward the incidence of COVID-19 cases, as well as the degree of immunity of the population, under a range of vaccine dosing regimens and assumptions related to immune responses. The original clinical trials of the vaccines are optimistic about the efficacy of a single dose of the vaccine. The study found that one-dose strategies may, as expected, reduce case numbers in the short term by more rapidly immunizing a greater number of individuals. However, if immune responses after one dose are less robust, subsequent epidemic peaks may be larger. Another important outcome associated with imperfect immune responses is the potential for viral immune escape. To start addressing this complex issue, the authors adopted an existing simple ‘phylodynamic’ model for viral immune escape.

The theory of viral immune escape predicts that in individuals with partial immunity, moderate selection pressure combined with sufficient viral transmission could drive viral evolution. The results strongly depend on the robustness of the immune responses following one and two vaccine doses, but the clinical parameters remain unknown. The researchers suggest randomization of dose intervals early in vaccination campaigns and careful monitoring of viral loads and immune markers in vaccinated individuals. One intuitive finding that the paper emphasizes is that very low rates of vaccine administration may be associated with larger case numbers and, possibly, more elevated potential for viral adaptation.

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