#16.831
Over the past couple of months we've seen several conflicting risk assessments on Omicron BA.4/BA.5, with one (see Kei Seto Lab Report) warning this emerging viral tag-team may be more severe (based on hamster studies) and can escape prior immunity (vaccine or acquired).
Despite some anecdotal reports, the jury is still out on any increase in severity, but we are seeing increasing rates of infection and hospitalizations in regions where BA.4/BA.5 are rising, and it appears that BA.4/BA.5 will likely become dominant worldwide over the next few months.Others (see ECDC Risk Assessment) have found increased transmissibility, but no evidence of BA.4 and BA.5 being associated with increased infection severity.
Of the two, BA.5 appears to have the growth advantage, and as of last Tuesday the CDC estimated that 13.3% of all U.S. cases are now due to that subvariant. On Friday Denmark's SSI reported Increased Cases & Hospitalizations With Rise of Omicron BA.5, and in the UK (where BA.5 is rising) their ONS (Office of National Statistics) reported a sharp rise in COVID cases over the past week.
The primary driver of BA.4/BA.5's enhanced transmissibility has been attributed to immune escape; its ability to evade much of the protection offered by vaccination and/or prior infection with BA.1.
Today we've a new Early Access report from the Journal Nature, which elucidates the ability of BA.2.12.1, BA.4, and BA.5 to evade prior immunity. As the manuscript is still being edited, I've only posted the abstract.
I'll have more after the break.
BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection
Nature (2022)Cite this article
We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.
Abstract
SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility over BA.2. The new variants’ receptor binding and immune evasion capability require immediate investigation.
Here, coupled with Spike structural comparisons, we show that BA.2.12.1 and BA.4/BA.5 exhibit comparable ACE2-binding affinities to BA.2. Importantly, BA.2.12.1 and BA.4/BA.5 display stronger neutralization evasion than BA.2 against the plasma from 3-dose vaccination and, most strikingly, from post-vaccination BA.1 infections.
To delineate the underlying antibody evasion mechanism, we determined the escaping mutation profiles2, epitope distribution3 and Omicron neutralization efficacy of 1640 RBD-directed neutralizing antibodies (NAbs), including 614 isolated from BA.1 convalescents. Interestingly, post-vaccination BA.1 infection mainly recalls wildtype-induced humoral memory. The resulting elicited antibodies could neutralize both wildtype and BA.1 and are enriched on non-ACE2-competing epitopes.
However, most of these cross-reactive NAbs are heavily escaped by L452Q, L452R and F486V.
BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1; nevertheless, these NAbs are largely escaped by BA.2/BA.4/BA.5 due to D405N and F486V, and react weakly to pre-Omicron variants, exhibiting poor neutralization breadths. As for therapeutic NAbs, Bebtelovimab4 and Cilgavimab5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, while the S371F, D405N and R408S mutations would undermine most broad sarbecovirus NAbs.
Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.
Although these findings are not unexpected - having just gotten my 2nd booster - this is obviously not the news I wanted to hear. Still, I'm hopeful the booster will provide a few months of protection and help keep me out of the hospital longer term.
Given what little we know about `long COVID' (see Nature: Long COVID After Breakthrough SARS-CoV-2 Infection), and what we don't know about the health impacts of repeated COVID infections, I'm still choosing to wear a face mask in public venues, and I expect to continue to do so for the foreseeable future.
COVID-19 continues to re-write our pandemic playbook, dashing previously held notions, and taunting us with myriad twists and turns. It does not seem inclined to go quietly into the night anytime soon, and it may have even bigger surprises in store for us.
With the expected rise of BA.4/BA.5, we could be facing a challenging summer and fall.
Stay tuned, and stay safe.
