Is the Current Bivalent Booster the Correct One? Studies Suggest it Isn't

Kevin Kavanagh, MD

The United States may be on the precipice of a rude awakening regarding the persistence and devastation of COVID-19. A perfect storm is brewing with the convergence of 3 untoward outcomes: The bivalent booster may primarily elicit imprinted immunity, a deadly brew of a plethora of immune escape variants is forming, and our public has thrown safety to the wind with few—if any—masking or bothering to optimize their immunity. All of this is in the background of new and disturbing data regarding the dangers of long COVID-19.¹

A recently posted study² from Columbia and the University of Michigan found that the immune response elicited by the new bivalent booster was similar to the old univalent booster for “all SARS-CoV-2 variants tested, including BA.4/BA.5.” This finding supports my concerns regarding the bivalent booster and the phenomenon of immune imprinting or “antigenic sin.” In other words, the type of immune response you produce is based upon the virus you were first exposed to (whether through vaccination or infection) and future exposures do little to modify the type of response elicited. A second study³ from Harvard also found comparable BA.5 antibody titers with the monovalent ancestral and bivalent boosters.

COVID-19 Variant compared with their fold evasion. (Credit: Stuart G. Turville)

 
I first discussed this concern in an Infection Control Today^® article⁴ regarding data presented before the Centers for Disease Control and Prevention's (CDC’s) September 2022 Association for Professionals in Infection Control and Epidemiology committee meeting. The safety of the booster has never been in question. What is debated is if it will be any more effective than the booster based upon the ancestral strain. The presented data, which was derived from mice, found that the monovalent BA.5 booster (which is not clinically available) produced a response to the ancestral strain which was similar to that of the ancestral monovalent booster. However, the monovalent BA.5 booster produced a 6-fold increase in antibodies to the BA.5 variant, as the hybrid Ancestral/BA.5 booster (which is clinically available) produced a 2.6-fold increase. With this data, one must wonder why the univalent BA.5 booster was not chosen for clinical use.
 
But this finding was in mice. The human laboratory data reported by the University of Michigan found that the response elicited by the bivalent booster was similar to the response elicited by the bivalent Ancestral/BA.5 booster for all SARS-CoV-2 variants.
 
This is not good news. The immune escape potential of the BA.5 variant and not having a refined immune response, places all of us at risk. What is even more concerning is that if our immune response is imprinted to the original virus we are exposed to, what will happen with the new, even more immune evasive variants which are in circulation? Currently, the BQ.1 and BQ.1.1 variants are even more evasive and comprise 27% of all sequenced specimens⁵ in the United States. The BA.4.6 and BF.7 are also slowly increasing their proportion in the reported specimens. And the XBB⁶ and BA.5.2.6⁷ variants are looming; both are circulating in the United States in low percentages. We are faced with a soup of variants⁸, which because of their high infectivity can search out the most suitable host to infect.
 
Stuart G. Turville, corresponding author of an article in Nature Microbiology⁹ regarding the characteristics of variants, posted the following graph on Twitter derived from their data on immune evasion.

There are concerns that the BQ.1 and BQ.1.1 may not only be more infectious but also more lethal as compared to the BA.1 (original omicron) variant.
Almost solely relying upon a vaccine/booster whose effectiveness appears to be imprinted in the past, to combat a virus which is progressively evading immunity, is unlikely to be an effective plan. We need to enact other strategies, such as masking and curtailing activities in high-risk venues.

To this end, the new CDC commercial entitled ”Just In Time: Updated COVID-19 Vaccines,”¹⁰ appears to be counterproductive. The commercial is designed to encourage vaccinations. No one is wearing a mask, even in crowded indoor places. The message I fear that is being transmitted is that if you are vaccinated all will be well and you do not have to take other precautions.

A screenshot of the CDC commercial. No one has masks on. (Credit: CDC)

 
I know of 5 individuals who have recently contracted symptomatic COVID-19 after receiving the bivalent booster. All had truly mild symptoms and did not develop long COVID-19. But the latter is always a concern, and it is the reason why we need to continue vigilance even if boosted, and if one becomes infected to seek medical care to obtain an antiviral therapeutic.

Should the new bivalent booster help? The answer is most assuredly “yes” but it is only 1 layer of armor. We also need to take additional steps. This means continuing to wear masks in high-risk settings and avoiding indoor crowded places. Even with the new bivalent booster, it is unwise to place yourself, without a mask, in a crowded elevator.

1. Have you recovered from covid-19, or just survived? Infection Control Today. Accessed October 31, 2022. https://www.infectioncontroltoday.com/view/have-you-recovered-covid-19-just-survived-
2. Wang Q, Bowen A, Valdez R, et al. Antibody responses to Omicron BA.4/BA.5 bivalent mRNA vaccine booster shot. bioRxiv. Published online October 24, 2022:2022.10.22.513349. doi:10.1101/2022.10.22.513349
3. Collier A Ris Y, Miller J, Hachmann NP, et al. Immunogenicity of the ba. 5 bivalent mrna vaccine boosters. bioRxiv. Published online October 25, 2022:2022.10.24.513619. doi:10.1101/2022.10.24.513619
4. The autumn covid-19 booster is here: is it safe and effective? Infection Control Today. Accessed October 31, 2022. https://www.infectioncontroltoday.com/view/the-autumn-covid-19-booster-is-here-is-it-safe-and-effective-
5. CDC. Covid data tracker. Centers for Disease Control and Prevention. Published March 28, 2020. Accessed October 31, 2022. https://covid.cdc.gov/covid-data-tracker
6. The CDC is now tracking a new immune-evasive Omicron variant spiking in Ukraine that’s evading treatment. Accessed October 31, 2022. https://news.yahoo.com/cdc-now-tracking-immune-evasive-175321321.html
7. The CDC is now tracking a new immune-evasive Omicron variant spiking in Ukraine that’s evading treatment. Accessed October 31, 2022. https://news.yahoo.com/cdc-now-tracking-immune-evasive-175321321.html
8. Callaway E. COVID ‘variant soup’ is making winter surges hard to predict. Nature. Published online October 28, 2022. doi:10.1038/d41586-022-03445-6
9. Aggarwal A, Stella AO, Walker G, et al. Platform for isolation and characterization of SARS-CoV-2 variants enables rapid characterization of Omicron in Australia. Nat Microbiol. 2022;7(6):896-908. doi:10.1038/s41564-022-01135-7
10. Just in Time: Updated Covid-19 Vaccines - :30. Accessed October 31, 2022. https://www.youtube.com/watch?v=W-vp45ItkkA