Canada has adopted a “first dose fast” approach to COVID-19 vaccinations, based on the National Advisory Committee of Immunizations (NACI) recommendation. Because of a limited vaccine supply and the ongoing pandemic, the recommendation is that jurisdictions should maximize the number of individuals benefiting from the first dose of the vaccine by delaying a second dose for up to four months after receiving the first.

The rationale is that partial protection for many is better than full protection for few. This strategy of delaying second doses may be working in some real-world circumstances. However, special consideration should be given to those in front-line health care settings who have only received one dose of the vaccine — and to whether or not the Canadian strategy of delayed second doses is reasonable.

Here is the issue: there are no data to support the inference that this partial protection from a single dose of vaccine will persist out to four months. For the approved RNA vaccines from Pfizer-BioNTech and Moderna, the prescribed dosing intervals are three weeks and four weeks, respectively. For the AstraZeneca DNA vaccine, the prescribed dosing interval can extend from four to 12 weeks.

Does this partial protection from a single RNA vaccine dose wane over time? Will the second dose, if delayed up to four months, offer the same level of protection from severe disease and death as that reported for the approved dosing schedule? The answers to these questions are unknown. Indeed, vaccine hesitancy may in part reflect concerns relating to the uncertainties surrounding a delayed second dose.

RNA vaccines are different from traditional vaccines, where generally a single dose confers protection from infection. As this protection declines, a booster vaccination is recommended, sometimes years after the initial vaccination. For the RNA vaccines, the first dose initiates the protection process, but is only complete after the second dose.

And it is highly likely that a booster will be required at a later date, to maintain the level of protection from infection. The first dose of the COVID vaccines triggers one type of early immune response, associated with T cells, to a greater extent than the antibody response. Indeed, most people — regardless of age — do not make a good antibody response to the first dose of vaccine, reflected in the incomplete protection observed. T cells contribute to, and are essential for, a robust antibody response. In fact, data show that there are one tenth as many T cells that can fight the virus in the absence of a second vaccine dose. The science informs us that the first dose induces a poor immune response compared with two doses.

SARS-CoV-2 is predominantly an airborne infection. Masking and distancing only reduce the risk of infection transmission; vaccination is the most effective strategy for protection. A vaccine dosing strategy that is not optimal will permit continued transmission. As highly transmissible variants of concern become the prevalent circulating strains, the partial protection from a single vaccine dose will further diminish.

Accumulating evidence indicates that the elderly and the immunocompromised (cancer patients, transplant recipients, those with autoimmune diseases) exhibit a diminished response even to a first dose of RNA vaccine. Although this will increase following the second dose administered in the three or four week dosing interval, susceptibility to infection and severe COVID-19 after the first dose is greater in these vulnerable populations than for healthy adults.

This prompted NACI to prioritize cancer patients and transplant recipients for their second dose at the prescribed shorter dosing interval. Unquestionably, decisions and directives are being made with the best intentions, and for the most widespread benefit. A limited vaccine supply demands we be prudent — the more so as we see provincial health care systems and front-line health care workers buckling under the strain of dramatically increasing COVID case numbers.

Can we risk only partially protecting front-line health care workers exposed to COVID patients on a daily basis and to procedures that create aerosols? The “first dose fast” approach needs to be amended to also prioritize them to receive their second vaccine doses earlier. This change needs to be an immediate federal government directive.

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Eleanor N. Fish is a professor in the University of Toronto’s Department of Immunology and emerita scientist, University Health Network. Pamela Ohashi is a professor in the University of Toronto’s Department of Immunology and senior scientist, University Health Network.





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