This evidence synthesis has been compiled by members of the CITF Secretariat and does not necessarily represent the views of all CITF members.

By Mercedes Yanes Lane

Due to vaccine shortages, researchers are considering alternative options to the standard recommended vaccination schedules allowing more people to be vaccinated at an earlier date. This UK study modelled different vaccination scenarios, including different dosing schemes, strengths of immunity generated, and the likelihood of developing escape variants. Researchers found that a single dose of a COVID-19 vaccine (that generates a strong immune response) together with a delayed second dose, is an effective epidemiological approach. However, if one-dose vaccinal immunity is weak, the outcome could be less-than desirable.


This study by researchers in the United Kingdom explored the implications of different vaccination schemes for COVID-19, together with the implications for viral mutations, in an immuno-epidemiological model for SARS-CoV-2 dynamics.

This team’s model helps to better understand the effects of different vaccine dosing schemes on the burden of cases. The authors found that a one-dose strategy (or a longer inter-dose period) may lead to a substantially reduced “first” epidemic peak of cases after the initiation of vaccination. However, if the immune response generated by the vaccine is weak, individuals remain partially susceptible, which then may lead to an earlier second peak.  This can be mitigated by ensuring that individuals receive a second dose, even if this is delayed. It is important to note that the benefits of a single dose strategy are diminished when vaccination rates are low (0.1% to 1% per week), given that not enough people in the population are immunized to prevent viral transmission.

As more variants of concern emerge, it becomes increasingly important to consider the effects of vaccination on viral mutations that can escape vaccine-induced immunity. When external conditions lead to the survival of variants (selective pressure), the findings from this model show that a one-dose strategy could lead to higher rates of variants that escape vaccine-induced immunity. Given these concerns, a two-dose strategy, even one with a longer delay between doses, is thought to be more effective taking into consideration that vaccinating as much of the population as early as possible is also needed. The authors of this study stress the urgency and importance of a rapid global vaccine deployment, as no one single strategy will be effective if immune escape variants spread rapidly.

The authors discuss important limitations to the models presented in this paper. The most important limitation: there are many factors that play a role in viral spread as well as in the development of variants of concern. These models only present a general indication of what different scenarios might look like. In places where SARS-CoV-2 infections are increasing, using a single dose approach may have a short-term effect in reducing incidence and prevalence. If one dose has a strong immunological effect, then delaying the second dose may also be beneficial. However, if vaccine-induced immunity is weak and antibodies diminish quickly after one dose, there is a risk that there will be a long-term increase in infections and potential for viral mutations. This can potentially be mitigated by a second dose of vaccine. The authors underline the importance of designing clinical trials to evaluate the strength and duration of immunity of different vaccination schemes in order to more effectively inform public policy.

Saad-Roy CM, Morris SE, Metcalf CJE, Mina MJ, Baker RE, Farrar J, Holmes EC, Pybus OG, Graham AL, Levin SA, Grenfell BT, Wagner CE. Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes. Science. 2021 March 09. DOI: 10.1126/science.abg8663