Early Lab Data Provide Glimpse Into Omicron’s Immune Escape

Preliminary data from a small study at a prominent South African lab have found a 41-fold reduction in neutralizing antibody titers for the Pfizer vaccine against Omicron.

Alex Sigal, PhD, of the Africa Health Research Institute (AHRI) — which played a key role in the initial sequencing of Omicron — and colleagues analyzed 14 plasma samples from 12 individuals fully vaccinated (two doses) with Pfizer.

While the geometric mean titer (GMT) for 50% neutralization was 1,321 against D614G, the wild type strain of the virus, GMT fell to 32 for Omicron, they reported in a medRxiv preprint that has yet to appear there but was posted on AHRI’s website.

That’s far more extensive than the threefold reduction in neutralizing antibody titers seen with the Beta variant, the researchers reported.

Still, Sigal noted that Omicron escape from neutralization was “incomplete” — mainly because five patients who were both previously infected and vaccinated still had “relatively high” neutralization titers against Omicron.

Indeed, a graph published with the preprint showed declines for both those who had vaccination alone or vaccination plus previous infection, but those with the latter (also referred to as “hybrid immunity”) appeared to maintain superior neutralizing antibody levels.

Experts commenting on Twitter noted this could indicate that booster shots could stand up well to Omicron. Pfizer also announced early Wednesday that its own data showed two doses of its vaccine had a more than 25-fold reduction in neutralizing titers against Omicron, but adding a booster restored those titers to close to what was seen with two doses against the wild-type virus.

“Given 3rd shot often provides 30-40x rise it might not be bad news, meaning not terrible,” tweeted Peter Hotez, MD, PhD, of Baylor College of Medicine.

“The hope is that, based on neutralizing data of other variants, 3-dose vaccinated neutralization of Omicron may be reasonable — MAY,” tweeted Shane Crotty, PhD, of the La Jolla Institute for Immunology, cautioning, however, that this remains “speculation for now.”

Crotty noted that the paper shows “neutralizing breadth in hybrid immunity is outstanding,” adding that a three-dose mRNA vaccine series “partially recapitulates that improvement in breadth.”

Sigal tweeted that the results were indeed “better than I expected of Omicron. The fact that it still needs the ACE2 receptor and that escape is incomplete means it’s a tractable problem with the tools we got.”

Yet others, including virologist Florian Krammer, PhD, of Mount Sinai hospital in New York City, noted that the drop was significant and raised concerns.

“Little activity was left in vaccinated individuals,” he tweeted.

Still, Krammer said that even if protection against infection would be significantly reduced, it would be likely that protection against severe disease “would remain reasonably high in all individuals with baseline immunity,” as non-neutralizing antibodies may target more conserved locations on the virus, and T-cell and memory B-cell activity also has a role to play.

The Sigal study used a live virus neutralizing assay (rather than a pseudovirus assay), and Sigal and colleagues started off by confirming that ACE2 was indeed required for Omicron entry into cells.

While six patients had confirmed prior infection with SARS-CoV-2 during the country’s first wave in addition to vaccination, the other six patients had no previous record of infection nor any detectable nucleocapsid antibodies. Two of the patients contributed samples from two different time points to get a total of 14 samples.

Last Updated December 08, 2021