Omicron infection shows poor results in boosting COVID immunity

June 16, 2022

According to a release by the Imperial College London, people infected with the Omicron variant don’t receive a strong immune boost against future SARS-CoV-2 infection.

These are the findings of a study published in the journal Science, led by researchers at Imperial College London, which looked at how the complex patchwork of immunity in the population following vaccination and previous infection influences our future protection against SARS-CoV-2.

A common assumption of the COVID-19 pandemic has been that a patient by being infected with the virus gains a natural immune boost. That boostwould potentially give that patient higher immunity  to fend off COVID infection in the future.

However, the latest analysis finds that Omicron provides a poor natural boost of COVID-19 immunity against re-infection with Omicron itself even in people who are triple-vaccinated.

The researchers found that Omicron is far from a benign natural booster of vaccine immunity, as we might have thought, but it is an especially stealthy immune evader.

In those who were triple vaccinated and had no prior SARS-CoV-2 infection, Omicron infection provided an immune boost against previous variants (Alpha, Beta, Gamma, Delta and the original ancestral strain), but less so against Omicron itself. Those infected during the first wave of the pandemic and then again later with Omicron lacked any boosting.

According to the team, their findings may help to explain why ‘breakthrough’ and repeat infections have been a common feature of the Omicron wave of the pandemic. However, they stress that vaccination continues to provide protection against severe disease and death.

It has been argued that even if antibody recognition of Omicron is poor, T cell immunity may be ready to fill the gap to achieve effective protection. However, the study showed poorer recognition of Omicron spike antigen by T cells in those who had been Omicron infected.

Professor Rosemary Boyton, from Imperial’s Department of Infectious Disease and lead author, said: “Getting infected with Omicron does not provide a potent boost to immunity against re-infection with Omicron in the future. Previous SARS-CoV-2 infection impacts on the ability to boost immunity against subsequent SARS-CoV-2 infection through a process called ‘immune imprinting’, and this may apply to sub-variants of Omicron including BA.4 and BA.5.”

Professor Danny Altmann, from Imperial’s Department of Immunology and Inflammation, said: “We have found that Omicron is far from a benign natural booster of vaccine immunity, as we might have thought, but it is an especially stealthy immune evader.

"Not only can it break through vaccine defenses, it looks to leave very few of the hallmarks we’d expect on the immune system – it’s more stealthy than previous variants and flies under the radar, so the immune system is unable to remember it.”

Previous work by the team found that patterns of immunity against SARS-CoV-2 are ‘imprinted’ on the immune system by infection history. Your imprint is determined by the number of vaccine doses you have received and the variant that you come in to contact with, resulting in different immunity across different individuals in the population.

Previous SARS-CoV-2 infection impacts on the ability to boost immunity against subsequent SARS-CoV-2 infection through a process called ‘immune imprinting’, and this may apply to sub-variants of Omicron including BA.4 and BA.5.

In the latest study, they looked at why there are so many Omicron breakthrough infections, even among people who have been triple vaccinated; how this is affected by previous infection history; and whether Omicron infection at least offers a ‘natural booster’ of COVID-19 immunity.

The team analyzed blood samples from UK healthcare workers who received three doses of mRNA vaccine, and who had different SARS-CoV-2 infection histories, to investigate antibody, T and B cell immunity against Omicron.

They found that people with no prior SARS-CoV-2 infection who then had Omicron showed enhanced cross-reactive immunity to previous variants – with enhanced B and T cell immunity against Alpha, Beta, Gamma and Delta – but they showed a reduced boosting against the Omicron spike protein itself.

Healthcare workers with prior Alpha infection showed a less sustained antibody response against Omicron. People infected during the first wave of the pandemic and then again with Omicron lacked any immune boosting, in an effect the researchers termed ‘hybrid immune damping’.

According to the researchers, the impact of immune imprinting means that after infection with Omicron people who had previously been infected during the first wave are not immune boosted against a subsequent infection with the variant, and potentially its subvariants BA.4 and BA.5.

Imperial College release