Adjusting Vaccines

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Last week I discussed the fast development of COVID-19 mRNA vaccines. Unfortunately, it is now becoming more and more apparent that early predictions about the elimination of the SARS-CoV-2 (COVID-19) virus by way of vaccination to achieve herd immunity were highly inaccurate. After a period of falling COVID-19 illness rates, the reemergence and spread of the delta variant necessitated a reexamination of some previous assumptions.

A more likely picture of our future with this virus comes into focus if we examine the well-known infection patterns of another respiratory virus, influenza. Early results from studies of mRNA vaccines against SARS-CoV-2 indicated that not only were they highly effective at preventing symptomatic infection, but that they were also effective in preventing asymptomatic infection, and therefore transmission. The effect on asymptomatic infections was a welcome surprise, because it is known that most vaccines for respiratory illnesses, including influenza, are “leaky” – that is, they allow some degree of asymptomatic infection and are better at preventing symptomatic infection and severe disease.

The initial data strengthened the hope that, at a certain level of population vaccination, transmission would cease completely. Eliminating COVID-19 seemed theoretically possible given that the original 2002 SARS virus ultimately disappeared. It turned out, however, that mostly due to the highly contagious delta variant plus waning immunity over time, asymptomatic infections and illness (albeit usually mild) in vaccinated people did occasionally occur. COVID-19 quickly became widespread due to the highly contagious nature of the virus and the emergence of variants.

Most experts now agree that it is not possible to eliminate COVID-19, therefore plans to deal with it over the long term should be developed. Pandemic and seasonal influenza provide the most appropriate models to aid in strategy going forward. In influenza, much like COVID-19, new strains and variants appear from time to time. This is called antigenic drift. Each year, the influenza vaccine is adjusted twice a year to account for the emergence, or anticipated emergence, of different strains or variants. With influenza, the goal of vaccination is to manage the inevitable outbreaks and reduce the rates of moderate-to-severe illness and death. Preventing mild disease, though important, is less critical. It is anticipated that the process of vaccine development for COVID-19 will follow a similar pattern as the makeup of the vaccine will be adjusted to account for waning immunity and antigenic drift. It is also anticipated that the COVID-19 vaccine will become annualized, similar to flu vaccine.

While there are similarities between SARS-CoV-2 and influenza, there are also meaningful differences. The most obvious difference is that, at present at least, the efficacy of the COVID-19 vaccine is much higher than the flu vaccine. For flu vaccine, effectiveness against laboratory-confirmed symptomatic infection is never higher that 50 to 60%, and some years is considerably below that. So, the goal of flu vaccine is not to prevent outbreaks, but to prevent serious disease and complications. Going forward, it is hoped that the SARS-CoV-2 vaccines can continue to be highly effective at preventing serious disease and death. How often they will need to be given and how effective they will continue to be remains to be seen.

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By Peter Galvin, MG

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