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Omicron Variant vs Pfizer Vaccine – First Data Available

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As confirmed cases of the novel variant, Omicron, continue to rise across the world, fears have been mounting as to whether this variant, which is “highly mutated”, could be more transmissible or deadly compared to previous variants, or able to evade vaccine-induced immunity.

A new pre-print study shared by Professor Alex Sigal’s laboratory at the Africa Health Research Institute is the first scientific data to be published on Omicron. The research by Sigal and colleagues investigated whether the variant escapes neutralization triggered by the mRNA-based vaccine, BNT162b2 (Pfizer–BioNTech). The team also explored whether Omicron neutralizes the ACE2 receptor to infect host cells. Let’s break down the findings. 

Omicron uses the same receptor – ACE2 – to enter and infect cells 

To explore whether Omicron is using the same “doorway” to enter cells, the ACE2 receptor, Segal and colleagues conducted experiments using human cell lines in a laboratory dish. Some of the human cell lines were engineered to express the ACE2 receptor, while others were engineered to not express ACE2. Omicron infected the ACE2 expressing cell lines but did not infect those lacking the receptor. This demonstrates that the novel variant is using the same entry route as previous SARS-CoV-2 variants.

Professor Paul Moss from the College of Medical and Dental Sciences, University of Birmingham, explained why this is good news in a comment to the UK Science Media Centre (SMC): “On the positive side, the virus has not evolved away from using the ACE2 receptor to enter our cells and as such antibodies that have been generated to block this interaction will not be completely negated.” 

Omicron vs Pfizer COVID-19 vaccine 

Next, the researchers looked at the ability to neutralize Omicron in two groups of individuals:

  • Six individuals that had received the Pfizer–BioNTech COVID-19 vaccine and had not previously been infected with SARS-CoV-2.
  • Six individuals that had received the vaccine in addition to previously being infected with SARS-CoV-2 and having detectable antibodies. 

The individuals that had previously tested positive for SARS-CoV-2 infection did so in the first wave of the pandemic in South Africa, during which the prominent form of the virus was D614G.

Plasma samples were collected from each of the 12 participants. 

“Geometric mean titer (GMT) FRNT50 (inverse of the plasma dilution required for 50% reduction in infection foci number) was 1321 for D614G,” the authors write in the paper. These samples therefore had very strong neutralization capabilities against this variant of SARS-CoV-2.

So what happens when the samples are tested against Omicron?

“GMT FRNT50 for the same samples was 32 for Omicron, a 41-fold decline,” the authors write.

While this figure might seem frightening, the researchers emphasize that neutralization escape by Omicron was not incomplete; five of the participants that had been previously infected – in addition to being vaccinated – demonstrated seemingly high neutralization titers against Omicron.

Sigal took to Twitter to express some relief that the data is “better than expected of Omicron”. 

Keep calm, get your booster and carry on 

“It is important to interpret the data cautiously, as the investigators themselves point out.  While the amount of virus-killing observed in the lab is reduced markedly – up to 40-times reduction – there is still measurable virus neutralization, especially in those who were vaccinated and previously infected,” Dr. Jonathan Ball, professor of molecular biology at the University of Nottingham, told the SMC. “This group effectively mimics what we would expect in people who had had two doses of vaccine plus a boost.”

Professor Penny Ward, independent pharmaceutical physician, visiting professor in pharmaceutical medicine, King's College London, added that, given the high number of mutations occurring in Omicron, this data is to be expected: “Similar in vitro reductions in neutralizing titers were observed previously with other strains, but did not result in a loss of clinical effectiveness particularly against severe disease,” she said.

“After a year’s experience with the covid vaccines, we know that lower levels of antibody, while being less effective at preventing infection, remain very highly effective at reducing hospitalization and mortality rates,” Ward said.

Segal and colleagues’ work is yet to undergo peer review, a rigorous process that analyzes the integrity and quality of the data before it is published. The study sample is also small to form conclusions from. More studies are required, but it is a starting point.

Ward emphasized that the important take home from this data is, “Don’t panic! Keep calm, get your booster when called and carry on.”

Reference: Cele S, Jackson L, Khan K et al. SARS-CoV-2 Omicron has extensive but incomplete escape of Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection. Submitted to medRxviv. https://www.ahri.org/wp-content/uploads/2021/12/MEDRXIV-2021-267417v1-Sigal.pdf.