Delaying second doses of COVID-19 vaccines can reduce positive cases

Delaying second doses of COVID-19 vaccines should reduce case numbers in the near term; however, the longer 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 and one or two vaccine doses, according to a study from McGill University and Princeton University published today in Science.

"Several countries, including the United Kingdom and Canada have stated that they will delay second doses of COVID-19 vaccines in response to supply shortages, but also in an attempt to rapidly increase the number of people immunized," explains Chadi Saad-Roy, a graduate student in the Departments of Ecology and Evolutionary Biology (EEB) and Quantitative and Computational Biology in the Lewis-Sigler Institute at Princeton and the lead author of the study.

The original clinical trials of the vaccines, plus subsequent epidemiology, are quite optimistic regarding the efficacy of the first dose. However, we are still uncertain how the strength and duration of immunity from a single dose (or the full two-dose course or natural infection, for that matter) will persist in the longer term."

Chadi Saad-Roy, Study Lead Author and Graduate Student, Departments of Ecology and Evolutionary Biology (EEB), Quantitative and Computational Biology, Lewis-Sigler Institute, Princeton

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 regimes and assumptions related to immune responses.

One dose may not always be enough

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.

"More optimistically, we find that as vaccine capacity increases, increasing vaccination rates or changing the dosing regime to closer to the recommended two-dose schedule can mitigate these longer term epidemiological effects, which is important for public health planning," adds Wagner.

Another important outcome associated with imperfect immune responses is the potential for viral immune escape. To start addressing this complex issue, the authors adapted a previous simple 'phylodynamic' model for viral immune escape, developed by co-authors Bryan Grenfell, Oliver G. Pybus, and Edward C. Holmes, along with other colleagues not involved with the current work.

This theory predicts that in individuals with partial immunity, moderate selection pressure combined with sufficient viral transmission could drive evolution.

Here, the authors explore this possibility along with a range of other scenarios, including the more optimistic case of minimal potential for adaptation in hosts with waned immunity following one or two vaccine doses.

"At least one variant has already emerged that may be adapted for partial immune escape," notes Holmes. "Simple theory underlines that the evolution and transmission of variants by infected hosts with intermediate levels of immunity may be important. Therefore, the strength and duration of immunity, and particularly the effect of these on retransmission, are key parameters to determine" adds Grenfell.

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.

"This strongly underlines the importance of equitable global vaccine distribution, as immune escape in one location will rapidly spread," explains C. Jessica E. Metcalf, a co-author on the paper, and an Associate Professor in EEB and the School of Public and International Affairs at Princeton and an associated faculty member at the High Meadows Environmental Institute.

"The models are relatively simple conceptually, but they illustrate the complexities of the problem and highlight the challenges that we still face," notes Michael Boots, a Professor of Integrative Biology at UC Berkeley who was not affiliated with the present study. "This important piece of work provides a framework that we can use to inform our approach going forward and moreover identifies the key knowledge gaps that we need to address," adds Boots.