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How well do non-mRNA vaccines work against Omicron and will vaccine inequity worsen?

Daniel R. Lucey, MD, MPH, FIDSA
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This week (Dec. 7-8) initial in vitro data on the decrease in Pfizer/BioNTech vaccine-induced neutralizing antibody against the Omicron variant has been rapidly shared, before peer review, by several laboratories, e.g., in South Africa, Germany and Sweden. One of the best summaries of these four studies, with links to each one, appeared Dec. 8 in Nature, written by Ewen Callaway (“Omicron likely to weaken COVID vaccine protection”).

No data, however, has yet appeared (as of Dec. 10 at noon ET) for any other vaccines. If some of these many other international vaccines, given to billions of people so far, have even lower levels of neutralizing antibody, then concern will be raised as to whether some current vaccines should be used at all against Omicron. If such concerns arise, then the ongoing crisis in global COVID vaccine inequity might worsen acutely.  

Immunologically-defined protection, by both neutralizing antibody and also by cytotoxic CD8+ T cells, is important especially to the key issue of clinical protection against severe disease, hospitalization and death.

All COVID-19 vaccines would ideally be evaluated across the spectrum of protection against Omicron, e.g., against any infection; against severe infection, hospitalization and death; against breakthrough infections with transmissible virus; and later against “long COVID” due to Omicron. 

Is there precedent for any of the first-generation non-mRNA or mRNA vaccines, all of which are based on the original virus sequences from December 2019, being reported not to protect against infection with one of the four prior variants of concern: Alpha, Beta, Gamma or Delta?

Yes, the New England Journal of Medicine published a paper by Madhi S. et al. from the renowned University of Witwatersrand in South Africa on March 16, 2021, titled “Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant,” which concluded:

“A two-dose regimen of the ChAdOx1 nCoV-19 vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 variant.”  

“Vaccine efficacy against this variant, analyzed as a secondary end point, was 10.4% (95% CI, −76.8 to 54.8).”

This variant B.1.351 was later named by WHO the “Beta” variant of concern. Importantly, however, no data regarding protection against severe disease, hospitalization or death could be produced from this small study. Nevertheless, these results from early 2021 resulted in a decision not to use this vaccine initially, but a different one, at that time in South Africa.  

This issue of protection against severe disease, and not only mild disease, will be pivotal in the imminent global policy decisions of how protective against Omicron each of the many international COVID vaccines are and whether global vaccine inequity will worsen acutely.


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