December 8, 2021

expert reaction to preprint of lab study from South Africa looking at omicron and extent of Pfizer vaccine immune escape

 A preprint, an unpublished non-peer reviewed study, suggests that the omicron variant of SARS-CoV-2 has extensive but incomplete escape of Pfizer-BioNTech vaccine elicited neutralization and requires ACE2 for infection.

Prof Jonathan Ball, Professor of Molecular Virology, University of Nottingham, said:

“This gives us the first glimpse of how vaccines might hold up against the omicron variant – if it starts to spread more widely by out-competing the delta variant.

“It is important to interpret the data cautiously, as the investigators themselves point out.  Whilst the amount of virus killing observed in the lab is reduced markedly – up to 40-times reduction – there is still measurable virus neutralisation, especially in those who were vaccinated and previously infected.  This group effectively mimics what we would expect in people who had had two doses of vaccine plus a boost.

“Whilst we do not fully understand what protective immunity looks like, the data should give us reassurance that the vaccine will still offer protection.

“The other thing to remember is that many of the vaccines also generate T cell immunity and we think that this will be less impacted by the high level of mutations that omicron has.

“Whilst this reduced antibody immunity might mean more people can be infected and have mild symptoms, I am still confident that the vaccines, especially after a boost, will still protect from serious disease.  That’s why we still need to get the message across, get vaccinated, get boosted, even if you have been infected before.”

Prof Paul Moss, Professor of Haematology, and Deputy Head of the College of Medical and Dental Sciences, University of Birmingham, said:

“These are important findings and can be interpreted in different ways.  The concerning finding is that antibody neutralisation is reduced by around 40-fold against Omicron compared to the original Wuhan virus.  This means that only 2.5% of the antibody neutralisation activity is retained but this sort of result was not unexpected given the mutational profile of the virus.  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.  Furthermore, emerging evidence from booster vaccinations shows that they are capable of generating very high levels of antibody which should potentially still provide valuable protection against infection.  Cellular immune responses should also remain largely intact.”

Prof Daniel Altmann, Professor of Immunology, Department of Immunology and Inflammation, Imperial College London, said:

“This new study offers a clear message about omicron susceptibility, similar to Delta but more so: those who are unvaccinated, or even 2-dose vaccinated, are likely to be highly vulnerable to infection.  However, those who’ve seen spike three times, which in this study was people who’d had infection plus two doses, but we might reasonably assume applies to a booster (third) vaccine dose, appear generally in the safety zone, even with a 41-fold drop.  So, an even stronger argument for getting boosters as widely and rapidly as possible.”

Prof Penny Ward, Independent Pharmaceutical Physician, Visiting Professor in Pharmaceutical Medicine at King’s College London, said:

“A very small study from South Africa looking at prevention of infection of cell cultures by the omicron variant has documented that higher concentrations of antibody are needed to neutralise the omicron variant than are needed to neutralise the initial strain of SARS CoV2.  Given the complex series of mutations found in the variant this is to be expected.  Similar in vitro reductions in neutralising titires were observed previously with other strains, but did not result in a loss of clinical effectiveness particularly against severe disease (see Lefevre et al ,Lancet; 2:.e685-e687.Abu-Raddad et al N Engl J Med. 385: 187–89).  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 hospitalisation and mortality rates.  So, to paraphrase Corporal Jones – Don’t Panic!  Keep calm, get your booster when called and carry on.”

Preprint title: ‘SARS-CoV-2 Omicron has extensive but incomplete escape of Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection’ by Sandile Cele et al. This work is not peer-reviewed.

The preprint is not yet posted on a preprint archive but is available here:

https://www.ahri.org/omicron-incompletely-escapes-immunity-induced-by-the-pfizer-vaccine/

https://www.ahri.org/wp-content/uploads/2021/12/MEDRXIV-2021-267417v1-Sigal.pdf

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

Prof Jonathan Ball: “Receipt of funding to develop next generation vaccines.”

Prof Penny Ward: “I am semi-retired, but I am owner/Director of PWG Consulting (Biopharma) Ltd a consulting firm advising companies on drug and device development. Between December 2016 and July 2019 I served as Chief Medical Officer of Virion Biotherapeutics Ltd, a company developing antiviral treatments for respiratory viral diseases. Previous employee of Roche, makers of tocilizumab (anti IL6 antibody) and CMO of Novimmune, makers of empalumab (anti IFN gamma antibody).”

None others received.