NEWS BRIEFING: First Aussie data on Omicron show why boosters are key

These two pre-prints are yet to be peer reviewed and are very quick responding experiments to the emergence of the Omicron variant. Results, however appear sound and well controlled, are from a great team of workers and thus likely reliable.

Outcomes indicate a substantial drop in the ability of antibody (from vaccination, or natural infection) to neutralise infection with the Omicron SARS-CoV-2 variant. Unfortunately, a number of commercial monoclonal antibody therapies are poor in neutralising Omicron, but the good news is that sotrovimab (available in Australia) is still effective. Of note, as highlighted in the press release from Kirby Institute from Prof Kelleher, our immune responses also are armed with T-cell immunity to protect against Omicron, so the antibody response is not the sole protective agent. The future modelling presented suggests that with two doses of BNT vaccine, protection against severe disease is lower against Omicron than the original SARS-CoV-2 – but still pretty good. Reassuringly, an mRNA booster is predicted to restore protection to very high levels against severe disease from Omicron.

Public health responses including masking, physical distancing and vaccination still remain appropriate courses of action but this data highlights the importance of getting a 3rd vaccine dose to maintain high levels of protection against viral variants.

Research from New South Wales Health Pathology at Westmead and the University of Sydney demonstrates in a small preprint study that a third (booster) dose improves neutralising antibody levels to SARS-CoV-2 strains, including Omicron. Although the booster vaccine responses to Omicron are about four times less than for the original SARS-CoV-2 strain, they still rise and so confirms the public health messaging that boosters are important for community protection.

These are important studies. The study on immune evasion confirms what we have seen from other studies, that there is a substantial reduction in protection from infection and vaccination compared to previous variants.

This is the first study I am aware of that looks at the effect of monoclonal antibodies. It shows that most (including Regeneron, which former president Trump was treated with) do not retain the ability to neutralise Omicron – which means they will not work. Fortunately, Sotrovimab does retain effectiveness, and this is one of the Monoclonals we have in Australia. Monoclonals can be redesigned for Omicron, but this emphasises the importance of investing in diverse therapeutic options, including the promising new antivirals such as Molnupiravir and Paxlovid.  We will see more variants emerge, and the Monoclonals have this limitation in that they are tailored for a specific antigen.

The immune evasion paper and the meta-analysis both come up with estimates very close to the ones released by Discovery South Africa – that effectiveness of two doses against symptomatic infection drops precipitously against Omicron compared to Delta, and effectiveness also drops against severe disease from over 90% for Delta to about 78-80% for Omicron. A booster drives effectiveness right up again.  This highlights the importance for Australia to achieve rapid and high 3rd dose coverage. A 5 -6 month wait is a long time while cases are surging, and we need to proactively allow boosting at 2-6 months.

Evidence is beginning to mount that neutralising antibody produced by vaccination against COVID-19 declines significantly over time. This decline is experienced also in individuals who have experienced both COVID-19 infection and vaccination.
 
Very few studies have been done to measure specific antibody concentration following vaccination and how this changes with time. This information is critical to determine the specific concentration required to afford enough protection to prevent significant illness (i.e. correlate of protection).
 
The emergence of the Omicron variant of COVID-19 has heightened the need for booster vaccination particularly in the absence of a complete understanding as to how this variant may elude immunity gained via vaccination and/or infection with the virus. Recent research from the Kirby Institute has shown that a significant antibody response was not maintained following two doses of either the Pfizer or AstraZeneca COVID-19 vaccine to neutralise the Omicron variant providing further evidence for the importance of booster vaccination.
 
It is however important to note that only antibody responses were considered in the study and that the cellular T-cell response is equally important. The study is important for our understanding of the immune response to vaccination and the protection gained against the virus.
 
Booster vaccination will help to prevent the likeness of severe illness and hospitalisation from the Omicron variant. The study also highlighted the ability of one commercially available antibody, Sotrovimab to neutralise Omicron which will be important clinically for treating immunocompromised or hospitalised patients who succumb to the variant.

There are many pieces of evidence right from the first study from Alex Sigal’s team in South Africa (which has shown up to 41 fold decrease in neutralising antibodies elicited from vaccines) up to the current Australian studies (15-20 fold decrease in neutralising antibodies) from vaccinated individuals (2 doses). This suggests that Omicron is more adept at infecting people who've already had COVID-19 or multiple doses of leading vaccines.

The heavily mutated variant also has a much higher transmissibility with a possible R value of more than 3, which is almost double that of Delta and clearly shows that Omicron has the capabilities to replace Delta as the dominant circulating strain. We are already seeing this pattern in the UK.

The good news from this and many more studies looking at efficacy of booster doses around the world is that current vaccines are still able to neutralise the virus IF BOOSTER DOSES are given. The studies have shown that neither vaccination with two doses of AstraZeneca nor Pfizer were able to stimulate an antibody response strong enough to neutralise Omicron. This is significant and supports the need for boosters to protect people from infection. This also means that there is a possibility for a mandate of 3 doses of vaccines including booster shot to be qualified as ‘fully vaccinated’ taking into account recent developments of this new variant. 

Despite the risks from Omicron, the overall public health strategy used throughout the pandemic remains effective and is of the utmost importance. We should not forget that we already have the ‘weapons’ (e.g., masks, social distancing, etc.) to reduce the risk of becoming infected. It should therefore be our main goal to slow down virus spread by adhering to the existing hygiene protocols and speeding up the vaccination process (which now has to include booster doses at all age groups).

Getting 3 doses of vaccines against Covid-19, in particular the Omicron variant, is the strongest form of protection until a variant-specific booster is ready. We know that variant-specific boosters are currently in the pipeline from various vaccine manufacturers and this can be part of the booster dose regiment in the future. Testing to identify potential asymptomatic spreaders and directing them to isolate should remain a pillar of the public health response to Covid-19. Increasing whole-genome sequencing of SARS-CoV-2 samples in circulation is another critical step in identifying and staying ahead of new mutations. It allows scientists to find variants that can escape the protection offered by vaccines. Without widespread genome sequencing, variants can spread undetected.