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

By Varun Anipindi

The COVID-19 pandemic has created an urgent need to manufacture and distribute vaccines rapidly and widely across the world. Currently, three products (two based on the mRNA platform from Pfizer- BioNTech, Moderna and one based on the adenoviral vector platform from AstraZeneca-Oxford) are being used under emergency-use authorization in vaccination programs around the globe. These manufacturers recommend two doses at specific timeframes to achieve optimal efficacy. However, given the pandemic’s scale and the unprecedented demand for these vaccines, countries including Canada are facing logistical challenges obtaining sufficient doses to adequately vaccinate their population. There has also been much ambiguity as well as public health concerns regarding the consequences of a delayed vaccine booster (2nd dose) shots. Under these circumstances, it is important to understand whether: 1) the interval between the vaccine’s prime and boost shots can be safely extended, and 2) whether individuals are effectively protected after the first dose prior to them receiving their second booster shot.

Two articles released by The Lancet journal on February 19 speak to these concerns.

The Oxford’s Vaccine Trial Group examined the influence of timing between the prime and boost doses of Oxford-AstraZeneca’s ChAdOx1 nCoV-19 vaccine in four randomized clinical trials from the UK, Brazil and South Africa. Previously, this vaccine had demonstrated a combined efficacy of 70.4% against SARS-CoV-2 infection following two doses spaced 4-12 weeks apart. In this new publication, they conducted additional analysis on these cohorts examining protection following a dosing interval of less than 6 weeks  or longer than 12 weeks. They demonstrated that a dosing interval longer than 12 weeks may provide better outcomes, without compromising any protection within the 3-month period between the prime and boost shots. The second booster showed increased neutralizing antibody levels, which may be implicated to play  an important role in long-lasting protection.  Vaccine efficacy for a >12-week interval was 81.3% compared  to 55.1% in those vaccinated at a <6 week interval. The researchers commented that this observation is consistent with the observations of greater efficacy and stronger immune responses observed for other vaccines against pathogens such as influenza, Ebola and malaria. Remarkably, a secondary observation in this analysis indicated that a single dose of the ChAdOx1 nCoV-19 vaccine demonstrates a 76% efficacy against symptomatic COVID-19 without significant waning in protection up to 12 weeks after the first dose. While this study was not designed to infer the ultimate longevity of protection after one dose, it provides valuable data to inform public health decisions.

Read the article here.

The effectiveness of one dose of either the Pfizer-BioNTech (BNT162b2 mRNA) or the Oxford-AstraZeneca (ChAdOx1 nCoV-19) vaccines in preventing COVID-19-related hospital admissions was studied among 5.4 million people in Scotland. Nearly 1.1 million people were vaccinated in this study and the vaccine effect (VE) of protection increased over time from day 28 to day 34 post-administration of the first dose of both vaccines. Both vaccines were extremely effective in curbing COVID-19 related hospitalizations (BNT162b2: 85%; ChAdOx1: 94%). While the study did not control for confounding factors such as secondary infections and age groups, it provides compelling evidence that the first dose of both platforms can have a population-level impact.

Read the pre-print article here.


A delayed second vaccine dose may confer better protection against COVID

Overall, both these studies suggest compelling evidence that can help stretch the limited vaccine supply and achieve the widest public health impact. This evidence supports remarks from Moderna which has also suggested dropping the two-dose requirement of their mRNA vaccine for people aged between 18-55 to double the overall available doses. Critically, these studies also support the notion that a longer dosing interval can lead to overall better outcomes. These sentiments were also echoed by Dr. Skowronski & Dr. De Serres in a letter to the editor published by the New England Journal of Medicine. This should also help alleviate some of the concerns associated with extended, and/or delays in the recommended prime-boost interval timings. However, additional consideration is needed with the rise in SARS-CoV-2 variants emerging globally. Higher levels of neutralizing antibodies elicited by the full course of two vaccine doses may be essential for conferring protection against some of the variants. It is unclear whether the benefit of increased vaccine coverage can synchronize with meeting the challenges posed by emerging variants. Further studies are required to help determine the overall consequence associated with alterations in dosing regimens.

Read the letter to the editor here.