Many of the current issues of public health and the research aspects of the future of COVID-19 vaccines and vaccine strategies have been topics of research and debate in the influenza vaccine literature for decades. Here we describe how the experience from the study of repeated influenza vaccinations can apply to the evaluation of COVID-19 vaccines and the prospect of future seasonal or periodic booster vaccinations.
it can be expected that, like influenza vaccines, additional COVID-19 vaccine doses will be needed to maintain optimal levels of protection. The frequency, timing, and groups prioritized for additional COVID-19 vaccine doses will depend on several factors, including the extent of vaccine efficacy decreasing relative to the most severe COVID-19 outcomes, the differential effect of vaccine efficacy decreasing on immunocompromised humans and the elderly. adults and the cost-effectiveness of different vaccine strategies.
In the few studies that were able to collect vaccine records for 4-6 previous years, immunogenicity and vaccine efficacy were highest among those with no or few previous vaccinations and lowest among those who were frequently vaccinated.
Although the third dose of COVID-19 mRNA vaccine produces the same level of vaccine efficacy as that obtained with a second dose of mRNA,
the antigenic distance hypothesis suggests that the efficacy of the COVID-19 vaccine after a fourth or fifth dose of vaccine may decrease if the vaccine antigen is unchanged and new antigenically distinct variants are circulating. The introduction of updated vaccine antigens may overcome preferential antibody responses to a marked infection (i.e., original antigenic sin) or the effects of a repeatedly administered vaccine antigen, as has been noted with influenza vaccines.
The second theory focuses on changes that may occur among individuals who are unvaccinated compared to those who are repeatedly vaccinated. Since vaccine-induced immunity blocks or reduces the risk of infection, the theory claims that the percentage of people who are unvaccinated with presumably stronger infection-induced immunity will increase over time (also referred to as the infection block hypothesis). Thus, estimates of the efficacy of the COVID-19 vaccine are likely to decrease as the difference in immune protection between those who have been vaccinated repeatedly versus those who have not been vaccinated decreases.
Fourth, the introduction of alternative vaccine types can improve immunogenicity and vaccine efficacy compared to the repeated use of the same vaccine technology. In one study, older adults receiving either a high-dose, adjuvanted or recombinant protein influenza vaccine had a superior serological and cell-mediated immune response compared with older adults who repeatedly received egg-based inactivated vaccines.
Research is needed to assess whether systematically alternating COVID-19 vaccine plans to introduce different vaccine types can enhance the effects of the vaccine.
The future of influenza and COVID-19 vaccines is now intertwined. Prolonged debates about influenza vaccine technologies, dose range, and strain composition may inform parallel debates about COVID-19 vaccines. The future of influenza vaccines will also be changed by the results of COVID-19 vaccines. Moderately effective inactivated influenza vaccines may be less acceptable to a public accustomed to highly effective COVID-19 vaccines. New vaccine technologies, such as mRNA, and the wider availability of second-generation influenza vaccines (eg high-dose, adjuvant and non-egg-based products) can significantly improve the average annual vaccine efficacy of influenza vaccines. The race to optimize the preventive benefit of both influenza and COVID-19 vaccines benefits everyone.
BJC is supported by a Research Grants Council Senior Research Fellow Scheme (HKU SRFS2021–7S03) from the Research Grants Council of Hong Kong Special Administrative Region, China and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, US Department of Health and Human Services (under contract 75N93021C00016); and consultants for AstraZeneca, Fosun Pharma, GlaxoSmithKline, Moderna, Pfizer, Roche and Sanofi Pasteur. MGT declares no competing interests. Opinions in this perspective are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. We thank Alicia Fry, Brandi Limbago and Michael Jung for their feedback on previous drafts of this comment.
Decreasing 2-dose and 3-dose efficacy of mRNA vaccines against COVID-19 associated emergency room and acute treatments and hospitalizations among adults during periods of delta and omicron variant dominance – VISION Network, 10 states, August 2021-January 2022 .
MMWR Morb Mortal Wkly Rep. 2022; 71: 255-263
Repeated annual influenza vaccination and vaccine efficacy: review of evidence.
Expert Rev Vaccines. 2017; 16: 1-14
Serial vaccination and the antigenic distance hypothesis: effects on the effectiveness of the influenza vaccine during A (H3N2) epidemics in Canada, 2010-2011 to 2014-2015.
J Infect Dis. 2017; 215: 1059-1099
Immune history and susceptibility to influenza virus.
Curr Opin Virol. 2017; 22: 105-111
Comparative immunogenicity of several enhanced influenza vaccine options for older adults: a randomized, controlled trial.
Clin Infect Dis. 2020; 71: 1704-1714
Published: April 28, 2022
© 2022 Published by Elsevier Ltd.