We tested live Omicron BA.2.86 subvariant isolated from a South African swab. As you'll see below, it was lurking somewhere for over a year, then started to spread rather slowly, maybe because it evolved similar immune escape to what is circulating now, but no better.
Here are representative results of sera from vaccinated people with breakthrough Omicron infection (subvariants BA.1, BA.4/5, and XBB family) from what we found:
We didn't find large differences in how these viruses replicated either. Similar size of infection foci after 20 hours (top) and cytopathic effect after 72 hours of infection (bottom) relative to XBB.1.5.
@richardneher did an analysis of where this variant may have come from
As you can see, BA.2.86 most closely resembles the sequences circulating in Southern Africa in early 2022. It then evolves but does not spread for over a year.
Based on these results, this variant is not a game changer. Our neut results are roughly similar to @BarouchLab, @BenjMurrell, and @yunlong_cao, though we saw less differences than @yunlong_cao and didn't see something that would indicate different infectivity vs. XBB.1.5
The long time this subvariant spent gaining mutations without spreading is likely because it was either a long infection in someone immunosuppressed or in an animal reservoir. We've seen these kinds of infections before:
We looked at whether #SARSCoV2 attenuates after extensive evolution in an immunosuppressed individual.
Submitted to medRxiv and available on sigallab.net while it gets screened. Bottom line is no.
It evolved to cause more cell death and cell fusion.
Starting with Omicron BA.1, there was a drop in severe disease because of increasing immunity and changes to the virus itself which decrease lower respiratory tract infection. The hope is that because the virus evolved extensively, it became milder, better adapted to us.
We tested the hypothesis that extensive evolution attenuates SARS-CoV-2 by checking viruses from a long-term infection from a person with immunosuppression because of advanced HIV disease.
We made movies of cellular infection, and this is what it looks like with no infection:
This took awhile given that as far as I know we were first to isolate the BA.4 and BA.5 live viruses and submitted the preprint to medRxiv in April. What was not liked by reviewers was the heterogeneity of our BA.1 infected cohort:
1) Most were unvaccinated (24 people) 2) The vaccinated group was split between those with J&J and Pfizer (8 Pfizer, 7 J&J) 3) We included 14 people living with HIV (13 with suppressed HIV viremia) out of 39 total BA.1 infected participants
Given the BA.4/BA.5 #Omicron sub-lineage wave currently happening in South Africa, I wanted to summarize a commentary we published a few weeks ago looking at disease severity in the Omicron BA.1 versus Delta variant waves:
Its important to do this now because disease severity is critical to understand the current BA.4/BA.5 wave in South Africa: while there seems a lot of infection in the community, this is not reflected in hospital admissions, or a great deal of testing for that matter.
I want to let you know that we have a paper out as accelerated article preview in Nature about how vaccination combined with #Omicron/BA.1 infection hybrid immunity enhanced the neutralizing immune response to other variants, including BA.2:
This is an expanded analysis relative to the preprint, which didn't contain the BA.2 neutralization data. The bottom line: if you get infected despite being vaccinated, the vaccine is still working for you. It gives you an advantage in neutralizing other variants (old or new)
The smallest immunity gap is for Omicron BA.1 itself, which was the infecting variant. The gaps get progressively larger, and are 10-fold or higher for Beta, Delta and ancestral virus. However, people who were vaccinated and then Omicron BA.1 infected have better BA.2 immunity.
We measured immunity against the #Omicron BA.4 and BA.5 variants by people infected with the original (BA.1) Omicron sub-lineage. Results consistent with these variants forming next infection wave.
Manuscript submitted to medRxiv and available here:
@KhadijaKhan24 in the Sigallab isolated the live Omicron sub-lineage BA.4 and BA.5 viruses and the first thing we tested was whether they escape neutralizing immunity from previous infection in the massive Omicron sub-lineage BA.1 infection wave which happened a few months ago.
We tested immunity in people infected in BA.1 who were unvaccinated (n=24), and in people previously vaccinated with Pfizer or J&J with breakthrough BA.1 infection:
We have new results that may give clues on how to make a more effective booster:
Beta infection combined with Pfizer BNT162b2 vaccination leads to broadened neutralizing immunity against Omicron
available now on sigallab.net and soon on medRxiv.
While vaccination protects against severe disease, its not so good against Omicron infection. The question is whether that is as good as it gets, or are there ways to improve, perhaps by modifying the spike sequence used in boosters.
This project, led by Sandile Cele in my lab, started out looking for South Africa specific factors which seems to have made the Omicron wave particularly mild here relative to other countries such as the US. One obvious difference is that SA had a Beta infection wave.