There is currently little data available to determine the vaccine escape potential of Omicron. Data that is available is preliminary and lacks thorough scientific review. However, preliminary studies are suggesting that no matter which vaccine you’ve received or whether you’ve previously had covid, all combinations of vaccination or prior infection show a significant reduction in neutralising antibodies against Omicron. That’s not to say that reductions in neutralising antibodies is associated with an increased risk of severe disease.

Antibody titers are only one measure of vaccine effectiveness. The effectiveness of other arms of the protective immune response against Omicron remain unknown. Monitoring real world data, such as hospitalisations, will reveal the overall effectiveness of vaccination against disease caused by Omicron.

Three doses of Pfizer will offer you a similar level of neutralising antibodies against Omicron as two doses did against the original Wuhan strain of the virus. As we have seen, this level of neutralising antibodies is associated with high levels of protection against severe disease from the Wuhan strain. Three doses of Pfizer may therefore provide a similarly high level of protection against disease caused by Omicron.

Many questions remain unanswered, for example how capable is Omicron of causing severe disease? Can Omicron outcompete Delta? Delta remains the dominant Variant of Concern globally. Vaccines and therapeutics that are effective against Delta must continue to be utilised.

If Omicron overtakes Delta as the dominant variant, and remains a threat to public health, then updates to mRNA vaccine formulations can be made with relative ease.

A New England Journal of Medicine study of over 800,000 participants reports that participants who received a Pfizer booster at least 5 months after a second dose of Pfizer had 90 per cent lower mortality due to Covid-19 than participants who did not receive a booster. Therefore, regardless of the virus variant, boosters will offer greater protection from severe COVID-19 and death.

In the past 36 hours, a swathe of preliminary data has emerged showing the drop in immunity against the Omicron variant. This data has come from studies looking at blood from people who have recovered from COVID-19 and/or been vaccinated against the disease.

All studies show less immunity against Omicron than against the original virus strain, however the reported drops vary widely. The estimates we have seen to date of people's immunity against Omicron range from half to one-fortieth of the immunity present against the original strain.

The work now begins to reconcile all the data together to establish a robust answer to this important question. Regardless of the number, it is clear that increased levels of immunity will be required to provide protection against Omicron, and therefore booster shots are now more important than ever to help achieve this.

The study Pfizer has reported indicates that the original two-dose vaccination may be less effective against the Omicron variant. This underscores all the more the need to get boosters to mitigate infection from Omicron and possibly other variants.

However, two caveats: First these findings are based on a very small sampling of fewer than 40 individuals who had received the Pfizer booster; and second, the findings reflect immune responses within only one month of this booster. We simply do not know the long-term efficacy of the Pfizer booster against Omicron or other variants. That will have to await continued studies.

The pre-print by Dr. Alex Sigal and his team in South Africa, showed there is a very large drop in neutralisation of Omicron by BNT162b2 [Pfizer/BioNTech] immunity relative to the original strain.

Specifically, they used human lung cells for the tests. They mixed a live virus (grown in the lab) with blood samples of six people who had two doses of Pfizer. They also mixed the virus with blood samples of six people with the two-dose series and a previous infection.

In order to assess vaccine 'effectiveness', the scientists counted the number of neutralising antibodies that attached to Omicron. Neutralizing antibodies play a significant role in our protection against infection, as they quickly recognise the virus and destroy it.

Importantly, the virus is destroyed before entering cells and, thus, cannot replicate. Because it can’t replicate, the person doesn’t get infected and doesn’t get the disease (i.e. symptoms). The more neutralising antibodies we have the better.

In this study, the scientists assessed how Omicron enters our cells and how many antibodies respond to Omicron compared to the original SARS-CoV-2 virus. What did they find?

1. This virus is using the same entry (you can call it a barrier/door/gate) into our cells (called ACE2 receptors) as before.

This is very good news because it means our tools (like vaccines) are still useful. If the virus found a different door, this may not have been the case. All of our vaccines would be rendered useless.

1. The virus is making a smarter key to that door (changing itself to open the door better)

Among people with the two-dose Pfizer series, neutralising antibodies took a significant hit —41 fold reduction— with Omicron compared to the original virus. This is far higher than we’ve seen with any previous variants of concern (Delta had a five-fold decrease; Beta had an eight-fold decrease). But Omicron’s decrease is not as bad as some expected. Among people with the two-dose series + previous infection, neutralizing antibodies took a hit from Omicron but are still relatively high.

This means we’re going to see an increase in breakthrough cases, especially among those with only the primary series. But this study gives me great hope that our boosters will help protect against Omicron. In addition, and importantly, neutralising antibodies are not our only defence. We have other antibodies, B-cell factories, and T-cells that will also help protect against severe disease and death. It will take time and more data to determine if we need an Omicron-specific booster.

Vaccines induce something called a 'polyclonal response'. Basically, the vaccine instructs the body to generate numerous shaped antibodies (with variable regions) that can connect to many different parts of the virus. Those antibodies are diverse in shape and cover the whole waterfront of the spike protein.

Mutations to those target sites raise the possibility that the vaccines would be less effective, not necessarily that they won’t work at all. Some antibodies may not attach, some antibodies may not attach as tightly, but others will. We saw this with Beta (another Variant of Concern). There were far fewer places for the neutralising antibodies to attach, but some still did.

Omicron has some of the same mutations as Beta and more. Hypothetically, there are still spaces for these antibodies to attach. That’s because of evolution competition. For the virus to survive, it has to change enough to outsmart our vaccines but cannot change enough where the virus’s key doesn’t fit at all.

If the virus is still using the same door with Omicron (ACE2 receptors), then our antibodies can probably still recognize parts of that key.

Boosters play a significant role here. They re-stimulate the immune system and increase the number of antibodies so more can attach and generate a much broader level of immunity. In other words, boosters can develop antibodies against more parts of the virus.

Also, the factories that make antibodies (B-cells) can adapt to new variants. Like a production factory, B-cells can modify their products as needed. So, while antibodies that are generated are highly specific, B-cells can adapt to any variant and create new specific antibodies.

There's a lot of variation from person to person when it comes to antibodies generated by vaccination.

Other studies looking at immune protection against variants have shown many of the COVID-19 vaccines create very strong immune protection that provides a cushion of extra immunity -- so that even if a variant escapes some of the immunity, there is plenty left to shield people from severe disease

The Karolinska team found a seven-fold reduction across 17 blood samples. They noted the impact of Omicron varied greatly between samples, and they used a version of Omicron that was artificially made in a lab instead of the live virus. A lead researcher for that group said the findings make Omicron “certainly worse than Delta", but, again, not as extreme as we expected.

We are seeing breakthrough infections of people who have been vaccinated, but the infections we’re seeing are very mild to moderate in South Africa.

I’m optimistic that the vaccines could still help prevent critical illness, despite significant drops in antibody levels. Vaccines also activate other parts of the immune system, particularly B- and T-cells that often confer protection against variants.  

Previous infection, followed by vaccination or booster, is likely to increase the neutralisation level and likely confer protection from severe disease in Omicron infection and the public should remain vigilant, prudent and not let their guard down, particularly during travel (winter season in certain parts of the world, festive season), and wear a mask when gathering indoors where the vaccination status of others is unknown.

I would really like to stress that those who are fully vaccinated should also seek a booster when eligible. I think we have good reason to believe that the vaccines are effective, if not as effective, and that with boosters, they’ll be quite effective.

Booster shots have been shown to drastically increase the level of antibodies that bind to the spike and also translate to better disease outcomes in the real world, as seen in Israel real world data.

In addition to this, Pfizer announced that results from an initial laboratory study demonstrating that serum antibodies induced by the Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) neutralize the SARS-CoV-2 Omicron variant after three doses. Sera obtained from vaccinated people one month after receiving the booster vaccination (third dose of BNT162b2 vaccine) neutralised the Omicron variant to levels that are comparable to those observed for the wild-type SARS-CoV-2 spike protein after two doses.

Sera from individuals who received two doses of the current COVID-19 vaccine did exhibit, on average, more than a 25-fold reduction in neutralisation titers against the Omicron variant compared to wild-type, indicating that two doses of Pfizer may not be sufficient to protect against infection with the Omicron variant. However, as the vast majority of epitopes targeted by vaccine-induced T cells are not affected by the mutations in Omicron, the companies believe that vaccinated individuals may still be protected against severe forms of the disease and are closely monitoring real world effectiveness against Omicron globally.

A more robust protection may be achieved by a third dose as data from additional studies of the companies indicate that a booster with the current COVID-19 vaccine from Pfizer and BioNTech increases the antibody titers by 25-fold.

According to the companies’ preliminary data, a third dose provides a similar level of neutralizing antibodies to Omicron as is observed after two doses against wild-type and other variants that emerged before Omicron. These antibody levels are associated with high efficacy against both the wild-type virus and these variants. A third dose also strongly increases CD8+ T cell levels against multiple spike protein epitopes which are considered to correlate with the protection against severe disease. Compared to the wild-type virus, the vast majority of these epitopes remain unchanged in the Omicron spike variant.

Conclusively, 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 the vaccine.

The Omicron variant of SARS-CoV-2 was first sequenced and identified in  November 2021 in South Africa and listed as a Variant to Concern by the WHO.  We do know that Omicron is the most heavily mutated Variant of Concern  discovered so far. Genomic testing in South Africa has indicated that there  are 50 mutations overall and more than 30 on the spike protein, which is the  target of most vaccines and the key the virus uses to unlock the doorway into  our body's cells. The receptor-binding domain (the part of the virus that  makes first contact with our body's cells) has 10 mutations in Omicron  compared to just two for the Delta variant.
  
A recent paper in pre-print from research undertaken in laboratories and  health institutes in South Africa indicates  that, based on the large  number of mutations in the spike protein, this variant will have considerable  escape from vaccine immunity from vaccinations and it is predicted that the  variant impacts transmissibility. Scientists in South Africa tested 14 plasma  samples from 12 participants, with 6 having no previous COVID-19 infection  nor any antibodies indicative of previous infection. The remaining 6  participants had a record of previous infection in the first infection wave  in South Africa. Results with Omicron show much more extensive escape and the  scientists report that previous infection, followed by vaccination or booster  is likely to increase the neutralisation level and offers protection from  severe disease in Omicron infection.
  
Results from initial laboratory studies by the  Pfizer-BioNTech on the COVID-19 Vaccine (BNT162b2) highlights that the  vaccine offers protection against severe disease after two doses from the  SARS-CoV-2 Omicron variant but that protection is increased 25 fold after  three doses. Tests undertaken on patient serum one month after receiving the  booster vaccination (third dose of BNT162b2 vaccine) neutralised the Omicron  variant to levels that are comparable to those observed for the  SARS-CoV-2 spike protein. Vaccinated individuals may still be protected  against severe forms of the disease after two doses and Pfizer-BioNTech are  closely monitoring impacts in the real world in real time against Omicron,  globally. The boosters increase immunity and the antibody levels are  associated with high efficacy against the variants.
 
 It is now imperative that we share vaccines globally with all countries  especially those in the developing world where populations have not received  a single dose, begin the booster doses starting with the elderly and those  who are immuno-compromised and roll out the vaccine to children."