Wednesday, September 21, 2022

Covid Vax vs Variants

The first RNA vaccines against Covid were based on the Surface, S or “Spike” protein from the reference genome of SARS-CoV-2, Wuhan-Hu-1, published in January 2020.  Since then, more-infectious variants have emerged; one, D614G, dominated but did not escape vaccine protection probably because its characteristic mutation is located outside the Receptor Binding Domain (RBD, 319-541). In the past year, delta variants were overtaken by omicron variants, which have numerous changes in the RBD, raising concern that they escape current RNA vaccines. 

Neutralization assays measure the ability of blood-borne antibodies to block viral infection of cells grown in a culture dish; they are thought to provide valid measurements of protection. These authors previously tested Covid neutralization with blood sera from 15 health care workers, 4 vaccinated with Moderna (mRNA-1273) and 11 with Pfizer-BioNTech (BNT162b2). They confirmed that a third dose (second booster) increased the neutralization activity (titer) against all strains, albeit 3-4 times weaker against subvariants compared with the ancestral version. Moreover, they showed the neutralization titers induced by 3 doses of the vaccines, and therefore presumably levels of protection provided, approximated those found in convalescent (sick) Covid patients (Fig 1 panel B vs C and D). 

In this letter, they studied 46 health care workers, 24 vaccinated and boosted with Moderna and 22 with Pfizer-BioNTech. Fourteen of the cohort were infected during the follow-up year. Figure S3 in the supplementary data confirm the protection provided by a third dose (second booster). They found that neutralization titers against all strains declined over time.  Titers from vaccinated people remained within a substantial fraction of those from infected people (shown, dashed vs solid lines). 

How much protection -- neutralization titer -- is enough? A paper published last year analyzing 7 different vaccines reported that neutralization titers are predictive of protection.  Neutralization titers of 20% of convalescent levels protected on average half of people against detectable infection; levels at 3% convalescent protected against severe Covid. Taken together, these results seem to support the value of the ‘old’ vaccines against the newer variants. 

Qu P, Faraone JN, Evans JP, Zheng YM, Yu L, Ma Q, Carlin C, Lozanski G, Saif LJ, Oltz EM, Gumina RJ, Liu SL. Durability of Booster mRNA Vaccine against SARS-CoV-2 BA.2.12.1, BA.4, and BA.5 Subvariants. N Engl J Med. 2022 Sep 7. 

1 comment:

Anonymous said...

More than 2 years into a worldwide pandemic, the leading medical journals should be publishing definitive, comprehensive, coherent results from hundreds if not thousands of participants and powerful meta-analyses of tens-of-thousands. Instead, we are grateful for fragmentary, disparate, quasi-anecdotal observations made from data obtained from a few dozen health care workers. Thanks anyway.

Also, how about occasionally showing controls, such as sera from unvaccinated participants? Controls matter. Moreover, it would provide a measure of antisera levels in the general community. Quibble. Maybe another letter.