Publication highlights

Does infection or vaccination induce nasal neutralising antibodies to SARS-CoV-2 variants? The Covid Surveillance Unit has developed a fast, easy method to test if antibodies in nasal mucosa stop SARS-CoV-2 replicating in cells in swabs from participants in the UCLH-Crick Legacy study. Both vaccination and infection boosted antibody levels in nasal mucus, and repeated vaccinations could enhance this. Importantly, the range of nasal antibodies differs from that in blood, which means current vaccines may not stop infections with new antigenically different variants. The methodology used in the study will make it easy to evaluate next generation vaccines, including mucosal vaccines.

The UKHSA SIREN study in collaboration with the Francis Crick Institute has identified that neutralising antibodies strongly correlate with protection against SARS-CoV-2 infection after vaccination.
SIREN participants are healthcare workers who provided monthly or quarterly blood samples throughout the study, as well as PCR testing every two weeks. The researchers compared antibody responses in 130 participants with Delta infection after a second vaccine dose (cases) to participants that were never infected before or after vaccination (controls). Antibody tests included measuring the total amount of antibodies developed from vaccination (anti-S) and specific neutralising antibodies against different live SARS-CoV-2 viruses that block infection.

Their findings demonstrated that, at seven days before infection, total anti-S antibodies were somewhat associated with protection: people were 29% less likely to develop an infection as antibody levels doubled. However, no specific threshold for protection was observed. In contrast, people with neutralising antibodies against the Delta variant above a threshold of 1 in 40 were 89% less likely to develop an infection.
This suggests that measuring specific neutralising antibodies can determine how susceptible a population is to infection. These findings are key for planning future vaccination strategies, and other public health measures around COVID-19.

In the UCLH-Crick Legacy study, the team asked why the UK didn't experience the predicted severe COVID wave from Omicron “escape variants” XBB and B.Q.1.1 (variants which arise from weaker immune responses to the vaccine) in winter 2022, unlike Singapore and the US. They used serum collected from Legacy study volunteers and tested for neutralising antibodies against these “escape variants” before and after the bilvalent vaccine - a type of vaccine which targets the original strain and Omicron strain.

Using data from the COVID Surveillance Unit’s specialist antibody tests against variants XBB, XBB.1.5 and BQ.1.1, they found that neutralising antibodies against these variants were boosted 3-4-fold in all participants after the bivalent vaccine. They also found any prior infection was a major contributor to high levels of neutralising antibodies against these new variants, but participants who hadn’t been infected still had neutralising antibodies against XBB after vaccination. Any 4th “encounter” with another Omicron variant, Spike, in 2022, boosted antibodies against these variants in patients who had had three vaccines. People who had been infected with the BA.1/2/5 variant had similar levels of antibodies as those who had been given the 4th vaccine. In summary, the UK’s targeted 4th dose vaccine policy by JCVI complemented widespread existing hybrid immunity in the wider UK population, protecting against the predicted severe wave of COVID-19 in UK winter 2022-3.

Researchers in the Kassiotis lab have shown that a specific area of the SARS-CoV-2 spike protein is a promising target for a pan-coronavirus vaccine that could offer some protection against new virus variants, common colds, and help prepare for future pandemics.

As part of the CAPTURE study, researchers in collaboration with the National Institute for Health Research (NIHR) UCLH Biomedical Research Centre found that antibodies generated in people who had received only two doses of either the Oxford/AstraZeneca vaccine or the Pfizer/BioNTech vaccine were less able to neutralise the Omicron variant as compared to the Alpha and Delta variants. They also found that antibody levels dropped off in the first three months following the second dose but that a third ‘booster’ dose raised levels of antibodies that effectively neutralise the Omicron variant.

Research from the Reis e Sousa lab has found a mechanism, previously thought to have disappeared as mammals evolved, that helps protect mammalian stem cells from RNA viruses such as SARS-CoV-2 and Zika virus. The lab suggest this could one day be exploited in the development of new antiviral treatments.

Two doses of the Oxford-AstraZeneca COVID-19 vaccine induce lower levels of antibodies that are able to recognise and fight the SARS-CoV-2 Delta variant (B.1.617.2) than against other strains.

The Legacy study team found that two doses of the Oxford-AstraZeneca vaccine generate lower levels of antibodies able to recognise the Delta variant, in comparison with the Pfizer-BioNTech vaccine. Their results also show that antibody levels vary considerably depending on likely prior infection with SARS-CoV-2.

An example of our work on COVID-19 and of the flexible and collaborative nature of the Crick, involving several labs within the Crick and our collaborating universities and university hospitals. In this work, we described the discovery of pre-existing binding and neutralising antibodies against SARS-CoV-2 in uninfected and unexposed individuals. These antibodies, likely induced by exposure to seasonal coronaviruses, are present in a small percent of adults but in the majority of children, consistent with the relative sparing of the latter from the severe form of COVID-19