When it Comes to COVID-19 Vaccines, Is Three a Crowd?

Volume 5, Issue 4

This week has brought renewed confusion regarding the Delta variant, indoor masking guidelines, and COVID-19 vaccinations. Many people undoubtedly saw the updated Centers for Disease Control and Prevention (CDC) guidance this week which stated that masks are now recommended for vaccinated persons who live in areas of high transmission. And most recently, CNN¹ broke news that Pfizer will soon release data that a third COVID-19 vaccine dose can lead to an “estimated potential for up to 100-fold increase in Delta neutralization post-dose three compared to pre-dose three.” In this week’s issue of Talking Therapeutics, we explore some of the data for third-dose boosters and tackle an issue related to health care inequity.

Point 1: It’s not all about the antibodies

The new study mentioned above from Pfizer is purely looking at levels of neutralizing antibodies, not actual protection in the form of lower rates of infection, hospitalization, and death. To illustrate this point, I draw upon my expertise in solid-organ transplantation. Multiple studies have shown that solid-organ transplant recipients have markedly impaired antibody responses to the commercially available COVID-19 vaccines.²

Yet, a recent paper in the American Journal of Transplantation found that despite poor humoral response, a real-world cohort of 557 solid-organ transplant recipients experienced a breakthrough infection rate of 0.65% with the currently available vaccines, with no reported fatalities or hospitalizations.³ This point is critical to reiterate: in a cohort of immunocompromised individuals (ie, in vivo) the standard vaccine regimen produced amazing results that are divergent from a blunted in vitro response. I say that it is critical because of the larger elephant in the room, which is…

Point 2: Vaccine access inequity must be addressed first

Currently only wealthy nations have vaccinated an appreciable number of their populations, while entire continents—such as Africa⁴—have barely begun. Arguably, the only reason that the Delta Variant exists is because vaccine access in India was insufficient. It therefore seems like a farcical solution to address the consequences of the Delta Variant by pumping more vaccines into the arms of those in the developed world rather than address the problem at its source by preventing outbreaks in the developing world. It is these outbreaks in the unvaccinated populations that fuel the development of new variants. It seems impossible to conceive that our ability to develop new boosters will outpace the development of new variants if we don’t first address vaccine inequity.

Until there is hard data (ie, not in vitro antibody levels) suggesting that the currently recommended two dose regimens are ineffective for the Delta Variant, we need to allocate these third booster doses to people who have yet to receive their first dose.

References:

1. Howard J. Pfizer data suggest third dose of Covid-19 vaccine 'strongly' boosts protection against Delta variant. CNN. July 28, 2021. https://www.cnn.com/2021/07/28/health/pfizer-third-dose-data-bn/index.html
2. Grupper A, Rabinowich L, Schwartz D et al. Reduced humoral response to mRNA SARS‐CoV‐2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus. American Journal of Transplantation. 2021. doi:10.1111/ajt.16615
3. Malinis M, Cohen E, Azar M. Effectiveness of SARS‐CoV‐2 vaccination in fully vaccinated solid organ transplant recipients. American Journal of Transplantation. 2021. doi:10.1111/ajt.16713
4. Africa’s COVID crisis deepens but vaccines are still far off. July 16, 2021. Accessed July 28, 2021. The New York Times. https://www.nytimes.com/interactive/2021/07/16/world/africa/africa-vaccination-rollout.html

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