On behalf of the TeamHealth Emerging Infectious Disease Task Force
COVID-19 vaccines, particularly the mRNA and related products are highly effective in decreasing serious disease, hospitalizations and death. Now that SARS-CoV-2 has become endemic, multiple questions are being raised regarding the use, timing and modification of the COVID-19 vaccines.
SARS-CoV-2, COVID-19, and mRNA Vaccines
Most Americans have now had at least one vaccine dose. Vaccine compliance rates range from <50 to >90% depending on the state. This includes a cohort of individuals having received a bivalent vaccine. The bivalent vaccines contain antigens from the initial “Wuhan” or Alpha variant strain as well as select Omicron sub-variants. These facts are particularly important when we consider the impact of hybrid immunity.
Vaccine Effectiveness Over Time in the SARS-CoV-2 Pandemic
The SARS-CoV-2 virus has an impressive ability to evade both natural and vaccine immunity as time passes. It is one of the most rapidly evolving viruses we have encountered. This, along with additional genome functions, makes this virus a formidable opponent for human immunity, both natural and vaccine related.
The mRNA vaccines were found to be extremely effective in the prevention of SARS-CoV-2 infection early in the pandemic (>90% in some studies). Yet as with most vaccines, over time that ability to prevent infection declined. At the same time, the ability of these vaccines to protect against severe infection and death remains high in excess of 80% – 90% in most studies.
However, this high level of protection is slowly deteriorating as the circulating SARS-CoV-2 virus mutates farther and farther from its initial Alpha antigen characteristics.
Preventing Infection and Preventing Serious Disease
There are differences in a vaccine protecting against SARS-CoV-2 infection versus prevention of serious disease, hospitalization and death. The currently approved mRNA vaccines remain effective in the prevention of most serious disease but are becoming less effective in the prevention of infection. Although these infections are typically mild, they still promote transmission of the disease. Importantly, even mild infections carry a risk of Long COVID (AKA: Post COVID-Conditions). And this risk can be substantial. We have covered this issue in the EIDT Long COVID project.
Should We Use the Influenza Approach for SARS-CoV-2?
Although we have become “comfortable” with seasonal influenza, when you really evaluate the behaviors of that virus, several interesting things become apparent. First, influenza has a significant global surge each year in a seasonal pattern. This pattern is very similar to the patterns starting to be seen with SARS-CoV-2. The viruses are present in the population year-round but have significant surges during particular times of the year. And these are global surges.
Additionally, the swarm of influenza virus circulating globally mutates at a rapid rate. Finally, an occasional influenza variant emerges that is able to inflict severe disease due to enhanced natural and vaccine immune escape. Anticipating and targeting such influenza strains for a different specific vaccine is critical to reduce morbidity and mortality. This behavior is also shared with SARS-CoV-2.
When to Give a COVID-19 Vaccine?
We want to time giving a vaccine such that the level of maximum protection coincides with any peak surge of that virus in the community. Influenza for example, has evolved a reasonably stable seasonal pattern with mostly winter surges. The current majority opinion is that a fall or early winter vaccination seems to make the most sense. Probably in conjunction with influenza vaccinations. So, what is the basis for that recommendation?
Currently the surges of SARS-CoV-2 seem to be more related to population behaviors, environmental stresses and vaccine compliance. These factors give us a general idea of when to time a vaccine to be most effective. Winter and holiday periods are when most of these influences merge. For now, the majority of vaccinologists and immunologists are thinking that a yearly modified vaccine given in the early fall is likely the best approach. This again follows the influenza pattern.
What Are the Primary Factors Impacting the Duration of Protection From a Vaccine?
The duration of protection any COVID-19 vaccine gives an individual person depends on a number of variables. Importantly we have to consider some of the following issues:
- How rapidly is the SARS-CoV-2 virus changing?
- How do those changes impact the antibodies created against it?
- How high are the current levels of neutralizing antibodies in an individual?
- How quickly can an individual generate an immune response to a new variant antigen?
- What level of protection against infection and serious disease is acceptable?
- What is the nature and strength of previous T-cell programming?
Other factors are of course also involved in immunity duration – and will need to be considered as well.
FDA VRBPAC and CDC ACIP Recommendations for New COVID-19 Vaccines
What are the current recommendations for COVID-19 vaccines? On June 15, 2023, the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) met to discuss COVID-19 vaccines and the potential of adding additional SARS-CoV-2 variants. After the discussion, the VRBPAC recommended updating COVID-19 vaccines by using the monovalent original Alpha “Wuhan” virus combined with the Omicron variant XBB.1.5 for vaccines by the fall of this year. The vote in the committee was unanimous.
The SARS-CoV-2 virus is developing a complex relationship with humans. It is a dangerous virus causing significant global disease and mortality. It is not influenza and does not share most characteristics of that also dangerous virus. However, it does share many epidemiologic behaviors with influenza. Those behaviors suggest that taking an influenza-like approach with periodic vaccinations of a variant targeted vaccine might be an effective tool to decrease SARS-CoV-2’s adverse impacts.
As always, more information is available on this topic in the references and resources here.
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Chavda VP, Vora LK, Pandya AK, et al. Intranasal vaccines for SARS-CoV-2: From challenges to potential in COVID-19 management. Drug Discov Today. 2021 Nov;26(11):2619-2636. (HERE)
FDA. Updated COVID-19 Vaccines for Use in the United States Beginning in Fall 2023. United States Food and Drug Administration – (HERE) Acc. 8/2/23
FDA. Recommendation for the 2023-2024 Formula of COVID-19 vaccines in the U.S. – (HERE) Acc. 8/2/23
CDC. COVID-19 Vaccinations in the United States. – (HERE) Acc. 8/2/23
FDA. COVID-19 Vaccines. – (HERE) Acc. 8/2/23
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Altarawneh HN, Chemaitelly H, Ayoub HH, et al. Effects of previous infection, vaccination, and hybrid immunity against symptomatic Alpha, Beta, and Delta SARS-CoV-2 infections: an observational study. EBioMedicine. 2023 Jul 27;95:104734. (HERE)
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Messina NL, Germano S, McElroy R, et al. BRACE trial. Off-target effects of bacillus Calmette-Guérin vaccination on immune responses to SARS-CoV-2: implications for protection against severe COVID-19. Clin Transl Immunology. 2022 Apr 22;11(4):e1387. (HERE)