Vaccine-related papers

Neutralisation of the Omicron variant

Many studies have been released in the last week, none yet peer reviewed, on antibody neutralisation of the Omicron variant. While all are small, generally involving sera from 10 to 30 individuals, the results are consistent. One or two vaccine doses neutralise the variant weakly, but a third dose greatly improves effectiveness.

The studies vary on how they assess neutralisation, and what other variants they compared Omicron with.

1. The Omicron variant was poorly neutralised by antibodies generated by the Moderna, Pfizer/BioNTech and AstraZeneca/Oxford vaccines. The strongest neutralisation activity was seen from those who had been infected with an earlier variant and been vaccinated.
2. Two doses of the Pfizer/BioNtech or AstraZeneca/Oxford vaccine are insufficient to give adequate levels of protection against infection and mild disease, but a subsequent Pfizer dose improved effectiveness to 70-75%.
3. A third Pfizer/BioNTech improves neutralisation, but to a level that is about four-fold lower than for an early strain.
4. Omicron was 49-to-84-fold less sensitive to neutralization than an early D614G variant after two Pfizer or Moderna doses, and 5-to-6-fold less sensitive than Beta. After a third dose, the reduction in neutralisation activity was only 6.5-fold.
5. Neutralisation of Omicron after two doses of the Pfizer vaccine was 35-to-40-fold lower than for an early Wuhan strain. No neutralising activity against Omicron was found for the  Coronavac vaccine.
6. Three doses of either mRNA vaccine improved neutralisation of Omicron, but still 4-to-6-fold lower than the early Wuhan strain. Weaker neutralisation was seen for the Johnson & Johnson vaccine followed up with an mRNA dose. Prior infection plus two vaccine doses resulted in the strongest neutralisation.
7. A third dose of the Pfizer/BioNTech vaccine boosted neutralising activity against the Omicron variant by more than 100-fold compared with two doses. Seven of nine monoclonal antibodies were not able to neutralise the Omicron variant, compared with only two being ineffective against the Delta variant.

In a more detailed study, the Omicron spike protein was found to be much more resistant to neutralisation compared to the original Wuhan strain. Sera from earlier infections with other variants showed a 30-to-60-fold reduction in neutralising activity against Omicron. Two mRNA vaccine doses were 30-to-180- old less potent.

Neutralising activity increased 38-to-154-fold in serum samples from previously infected double vaccinated individuals, or those who had three mRNA doses. The paper has not yet been peer reviewed.

Omicron’s receptor binding domain (RBD) shows a greater ability to bind to the ACE2 receptor than the RBD from the original Wuhan strain, but is less than the Alpha variant’s. However, the Omicron RBD is also able to bind to the mouse ACE2 receptor, an ability not seen in other variants.

The same study reports that sera from people who had two doses of the mRNA or AstraZeneca vaccines had a 30-40-fold lower level of neutralisation activity against Omicron, compared with the Wuhan strain. Sera from people vaccinated with the Johnson & Johnson/Janssen, Sputnik V or BBIBP-CorV showed no neutralising ability against Omicron.

Twenty six of 29 monoclonal antibodies were unable to bind to the Omicron RBD. However, several monoclonal antibodies that bind to other parts of coronaviruses were able to neutralise Omicron. This study has not yet been peer reviewed.

Other emerging Omicron information

SARS-CoV-2 T cells are still likely to be able to recognise the Omicron variant. CD8+ T cells from 30 previously infected people could still bind to the variant, and so confer significant protection. The paper has not yet been peer reviewed.

A study from Hong Kong reports that the Omicron variant can infect and replicate 70 times faster in the upper respiratory tract than earlier variants. However, infectivity in the lungs appears to be considerably lower. The information was provided in a press release, and hasn't been peer reviewed.

Eric Topol has created an electronic newsletter discussing recent Covid research. A recent edition discusses the information emerging about transmissibility and immune evasion of the Omicron variant.

The Science Media Centre published an Expert Review on the rapid spread of Omicron.

Comparing the effectiveness of the mRNA vaccines

A study has found that the Moderna vaccine is slightly more effective than the Pfizer/BioNTech vaccine, supporting results from other studies. It reports that the odds of having a symptomatic infection after receiving two doses of the Moderna vaccine was 40% lower than for the Pfizer vaccine. Overall though both vaccines are very effective.

Effectiveness for both vaccines declined about 20% between December 2020-May 2021 and July-September 2021. In the latter period the effectiveness against symptomatic infection for Moderna was around 76%, and 64% for the Pfizer vaccine. The authors consider that a variety of reasons contribute to reduced effectiveness later in 2021. The paper was published in Med.

Waning mRNA vaccine immunity over time

A review of studies of mRNA vaccine effectiveness over time found that peak humoral (antibody) response was reached 21-28 days after the second dose, with antibody levels in sera progressively declining over subsequent months. This pattern appears to be consistent regardless of age, sex, comorbidities, and whether people had had Covid-19. The paper has not yet been peer reviewed.

High levels of effectiveness in Novavax Phase 3 trial

Phase 3 clinical trial results for Novavax indicated 90% efficacy against infection, and 100% efficacy against moderate to severe disease. There were no vaccine safety concerns in the two months after vaccination. The trial was conducted mostly when the Alpha variant was dominant. The paper was published in the New England Journal of Medicine.

Potted summaries of vaccine & Covid highs and lows in 2021

A news article in Nature summarises some of the key vaccine successes, failures and impacts in 2021. While a timeline of Covid-19 was published in Nature Medicine.

Non-vaccine-related papers

Covid pills

A news article published in Nature discusses the implications of the poor effectiveness of Merck’s molnupiravir Covid pill, and concerns about potential long term safety risks of this therapy.

On the other hand, Pfizer reports that its Covid pill, Paxlovid, is 89% effective at preventing hospitalisations and death in high risk patients. Effectiveness was not as good for those classed as having a lower risk of hospitalisation before treatment. Their symptoms were not substantially relieved, although they had around a 10-fold lower viral load.

The information was made available in a press release. StatNews has a discussion of the results.

40% of people may have asymptomatic infections

Forty per cent of people may remain asymptomatic after infection. This conclusion is based on a review of 95 studies, covering 30 million people. Higher percentages of asymptomatic cases were found in studies of pregnant women, air and cruise ship travellers, and nursing home residents, which probably reflects more intensive testing.

Higher proportions of asymptomatic cases were seen in younger age groups. The studies used were published before February 2021. The paper was published in JAMA Network Open.

Immune imprinting from other coronavirus infections can affect Covid response

Earlier infections with human coronaviruses may hinder development of immune responses to SARS-CoV-2. This is due to “immune imprinting”, where the human coronavirus antibodies are preferentially stimulated following a SARS-CoV-2 infection, resulting in reduced neutralisation. The study involved mostly women of Causacian ancestry who had mild or moderate symptoms, so the results may not apply to everyone. The paper was published in Cell Host & Microbe.

Different variants generate different immune memory

Immune memory can differ depending on what variant people are infected with. In this study it was found that antibodies generated in response to a natural infection had different levels of neutralising effectiveness on different variants. This has implications for future vaccine developments. The paper was published in Science.

Behavioural science lessons from the pandemic

An Opinion published in The British Medical Journal identifies four main lessons learnt from behavioural science during the pandemic. Trust is a key factor in effective responses. The opportunities and capabilities to adhere to pandemic measures are much lower for the economically disadvantaged, so more effort needs to be directed at reducing inequalities. Clarity and consistency of messages is critical. Pandemic preparedness needs to be focused on protection over restriction, this includes better support for working from home and sick pay.

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The Research Tracker is prepared by Dr Robert Hickson for the Science Media Centre NZ.