Researchers show potential benefits of delaying second mRNA COVID-19 vaccine dose

The currently approved mRNA vaccines from Moderna and Pfizer-BioNTech help create neutralizing antibodies against the severe acute respiratory syndrome (SARS-CoV-2) spike protein. Both companies designed their vaccines to be delivered in two doses.

However, given the limited supply of vaccines worldwide, a new modeling study has suggested that vaccinating more people with the first dose and delaying the second could be an alternate route to achieving population immunity that could reduce mortality rates.

Over 115 million cases of coronavirus disease 2019 (COVID-19) and over 2.5 million deaths have been reported since SARS-CoV-2 was first detected in Wuhan, China, in December 2019. The study findings would help with vaccine distribution efforts and potentially prevent death by delivering partial immunity to more people.

By evaluating the time to reach a set immunity level within the entire population (rather than solely focusing on the population immunity gains at a set time), the above modelling shows that time to reach herd immunity could be shortened by 1.5 weeks with a 6 week spacing regime, 4.5 weeks with 12 week spacing, and 10.5 weeks with 24 week spacing, independent of vaccine supply.”

The study “Modelled Optimization of SARS-Cov-2 Vaccine Distribution: an Evaluation of Second Dose Deferral Spacing of 6, 12, and 24 weeks” is available as a preprint on the medRxiv* server, while the article undergoes peer review.

Modeling population immunity

The second dose of the mRNA vaccine was tested 3 weeks from the first dose. In this study, the researchers created a model to investigate how population immunity would be affected if people delayed their second dose by 6 weeks, 3 months, or 6 months.

Their analysis assumes that the population would be receiving 10% more vaccine shipments per week, with the total population fully immunized in 14 months.

Based on Pfizer-BioNTech’s phase III trial data, one dose of the vaccine should produce a 93% immunity, with the second boosting it to 95%. The researchers replicated this number in their estimates and measured immunity effects 2 weeks after doses were administered.

Population immunity was higher in people who delayed the second dose

Researchers found that every group that delayed the second dose by more than 3 weeks reached population immunity. Although, timing mattered.

People given the second dose after 3 months were twice as likely to experience immunity benefits than a person delaying the second dose for 6 weeks. People who delayed the dose for 6 months experienced the highest benefit towards population immunity.

Vaccine supply influences time to reach population immunity

Reaching population immunity depended on having a sufficient vaccine supply for 60 weeks. In reality, vaccine supply is limited worldwide, and many third-world countries are lagging in vaccination efforts.

Alternatively, for regions expecting to take longer than a year to vaccinate their population, lower gains with population immunity would be expected if the same spacing regimen was used.”

The researchers suggest having consistent vaccine shipment has a high effect on achieving population immunity after delaying the dose for 12 weeks. In this case, a 24-week delay in the second dose may not be needed as the whole population should receive their first dose after 24 weeks.

Delaying second vaccine dose is safe for people with prior COVID-19 exposure

The findings may also change who is prioritized for the vaccine. While high-risk groups such as the elderly or people with comorbidities should be on the top of the list, the results suggest a minimal benefit to vaccination patients who have previously recovered from COVID-19.

Because of natural immunity from prior exposure, recovered patients fall into a low-risk group as they appear to be 94% less susceptible to another coronavirus infection. Giving the second vaccine dose boosts their immunity by only 2% or 3% compared to the 93% boost in immunity for a person never exposed to SARS-CoV-2.

Results suggest changes to vaccine distribution policies

The researchers suggest delaying the second dose could increase the number of vaccinated people reaching population immunity or shortening the amount of time to reach population immunity. Although, this depends on the vaccine supply available in the area.

They conclude health policy reform on vaccine rollout is needed to prevent further infection and death.

Suggested changes would include deferring COVID-19-recovered patients from receiving the first dose vaccination until everyone has received at least one dose. Excluding high-risk groups, results suggest it is safe enough for people to defer their second dose until everyone has their first.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Jocelyn Solis-Moreira

Jocelyn Solis-Moreira graduated with a Bachelor's in Integrative Neuroscience, where she then pursued graduate research looking at the long-term effects of adolescent binge drinking on the brain's neurochemistry in adulthood.