Virus World

The emergence of the highly divergent SARS-CoV-2 Omicron variant has jeopardized the efficacy of vaccines based on the ancestral spike. The bivalent COVID-19 mRNA booster vaccine within the United States is comprised of the ancestral and the Omicron BA.5 spike. Since its approval and distribution, additional Omicron subvariants have been identified with key mutations within the spike protein receptor binding domain that are predicted to escape vaccine sera. Of particular concern is the R346T mutation which has arisen in multiple subvariants, including BA.2.75.2 and BQ.1.1.

Using a live virus neutralization assay, we evaluated serum samples from individuals who had received either one or two monovalent boosters or the bivalent booster to determine neutralizing activity against wild-type (WA1/2020) virus and Omicron subvariants BA.1, BA.5, BA.2.75.2, and BQ.1.1. In the one monovalent booster cohort, relative to WA1/2020, we observed a reduction in neutralization titers of 9-15-fold against BA.1 and BA.5 and 28-39-fold against BA.2.75.2 and BQ.1.1. In the BA.5-containing bivalent booster cohort, the neutralizing activity improved against all the Omicron subvariants. Relative to WA1/2020, we observed a reduction in neutralization titers of 3.7- and 4-fold against BA.1 and BA.5, respectively, and 11.5- and 21-fold against BA.2.75.2 and BQ.1.1, respectively. These data suggest that the bivalent mRNA booster vaccine broadens humoral immunity against the Omicron subvariants.

Preprint in bioRxiv (Nov. 1, 2022):

 https://doi.org/10.1101/2022.10.31.514636 

The Omicron coronavirus variant partly escapes the protection offered by the Pfizer vaccine, but people who have been previously infected and then vaccinated are likely to be well protected, researchers working in South Africa reported Tuesday.  Boosters are also likely to protect people, Alex Sigal of the Africa Health Research Institute in Durban, who led the study team, told CNN. It's the first experiment to directly look at how the Omicron virus might behave in vaccinated people. Tests in lab dishes using samples from 12 people who had been fully vaccinated with Pfizer's vaccine showed the Omicron variant could evade the immune protection built by the vaccine -- but not completely. "There is a very large drop in neutralization of Omicron by BNT162b2 [Pfizer/BioNTech] immunity relative to ancestral virus," Sigal said on Twitter. "Omicron escape from BNT162b2 neutralization is incomplete. Previous infection + vaccination still neutralizes," he added.  The findings are good news, Sigal told CNN. "I thought this news was very positive. I expected worse," Sigal said in a telephone interview. The mutations that characterize the Omicron variant, he said, looked like they could allow it to evade the immunity offered by vaccines to a greater extent.

Pfizer and BioNTech said three doses of their Covid-19 vaccine neutralize the Omicron coronavirus variant, according to the results of an initial laboratory study.  The data showed a third dose of the vaccine increases neutralizing antibodies by 25-fold compared with two doses, strengthening the case for and need for booster shots. The preliminary data suggest three doses provide a similar level of antibodies as is observed after two doses against other variants that emerged before Omicron, the companies said. Two vaccine doses showed a 25-fold reduction in neutralizing antibodies against Omicron compared with other variants, which they said suggested two doses “may not be sufficient” protection.  “Although two doses of the vaccine may still offer protection against severe disease caused by the Omicron strain, it’s clear from these preliminary data that protection is improved with a third dose of our vaccine,” Pfizer (ticker: PFE) CEO Albert Bourla said in a statement. The companies added that the development of an Omicron-specific vaccine was progressing and is expected to be available by March 2022, if such an adaptation ends up being needed. “The takeaways from Pfizer’s update underscore our belief that the durability of Pfizer’s vaccine sales for Covid-19 remain underappreciated by the Street,” Cantor Fitzgerald analysts said. They rate the stock as Overweight with a target price of $61, implying an 18% upside to Tuesday’s closing price.

Another study, published late Tuesday, suggested that Pfizer’s Covid-19 vaccine offers partial protection against the Omicron variant. The small South African laboratory-based study suggested that the variant escapes antibody immunity induced by the Pfizer-BioNTech vaccine but that “considerable immunity” is retained.  “It is likely that lesser vaccine-induced protection against infection and disease would be the result,” said Africa Health Research Institute’s executive director, Prof. Willem Hanekom. “Importantly most vaccinologists agree that the current vaccines will still protect against severe disease and death in the face of Omicron infection,” he added. The study was small, including blood samples from just 12 participants, but it is the first scientific data into the efficacy of vaccines against the Omicron variant. The loss of immune protection is “robust but not complete,” head of research Alex Sigal said, adding that a good booster shot would decrease the risk of infection, especially of more severe disease.  The study concluded that previous infection followed by vaccination of booster was likely to provide protection. It has been a volatile couple of weeks for Covid-19 vaccine makers, as investors battle to assess the impact of the Omicron variant while waiting for answers to crucial questions. Moderna (MRNA), Pfizer and Novavax (NVAX) were among the sharpest fallers in U.S. premarket trading on Wednesday. That is after plunging Monday and rallying on Tuesday. But Pfizer stock reversed course following the study results and was trading 0.4% higher.

Press release by Pfizer (Dec. 8, 2021) available at:

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-provide-update-omicron-variant