A third "booster" dose of the COVID-19 vaccine successfully raises levels of antibodies that neutralize the Omicron variant, according to laboratory findings from the Francis Crick Institute and the National Institute for Health Research (NIHR) Biomedical Research Center ) UCLH, published today (Wednesday) as a research letter in The Lancet .
The researchers found that antibodies generated in people who had received just two doses of the Oxford/AstraZeneca vaccine or the Pfizer/BioNTech vaccine were less able to neutralize the Omicron variant compared to the Alpha and Delta variants.
They also found that antibody levels decreased in the first three months after the second dose, but that a third "booster" dose raised the levels of antibodies that effectively neutralize the Omicron variant.
In people who had received all three doses of the Pfizer/BioNTech vaccine, antibody levels against Omicron after a third dose were similar to those previously achieved against Delta after just two doses. Overall, antibody levels were almost 2.5 times higher against Omicron after three doses compared to after two.
Higher levels of antibodies against the Omicron variant were also found in people who received two doses of either vaccine and also reported having previously had COVID-19 symptoms, compared to those who had not previously had COVID-19 symptoms.
While antibody levels alone do not predict vaccine effectiveness, they are a very good indicator of protection against severe COVID-19. This study confirms that three doses of the COVID-19 vaccine are essential to increase antibodies to measurable levels and maximize the amount of protection against severe disease and hospitalization.
The researchers have submitted their findings to the National Genotype-to-Phenotype Virology Consortium (G2P-UK), the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) and the Joint Committee on Vaccination and Immunization (JCVI).
As part of the SARS-CoV-2Legacy study, led by Crick and partners at UCL and University College London Hospitals NHS Foundation Trust (UCLH), healthcare workers and staff at the institutions have been regularly donating blood and swab samples to That researchers can track the changing risk of infection and response to vaccination.
The Legacy team analyzed 620 blood samples from 364 people who enrolled in the study. They used robust high-throughput viral neutralization assays, developed at the Crick, to test the ability of antibodies to block virus entry into cells, so-called "neutralizing antibodies", against different variants of SARS-CoV-2, including Omicron .
Higher antibody titers (the highest dilution level that still blocks 50% of virus infection in the laboratory) are a good predictor of vaccine effectiveness and greater protection against COVID-19.
Importantly, they also included in their analysis synthetic neutralizing antibodies that are currently in clinical use for the treatment of COVID-19, to test whether these synthetic antibodies have neutralizing activity against SARS-CoV-2 variants, including Omicron.
Researchers found that Xevudy ( sotrovimab ), a recently approved synthetic monoclonal antibody used to prevent and treat patients at risk of developing severe COVID-19, was able to neutralize the Omicron variant.
Dr Emma Wall, UCLHI infectious diseases consultant and lead clinical research fellow for the Legacyst study, said: “People who have queued outside vaccination centers should be reassured that a vaccine booster is the best option.” way to protect them from Omicron. And for people who haven’t yet received a booster or even a first dose, it’s not too late."
“This new variant can overcome the immune blockade established by two doses of the vaccine, but fortunately, after the third dose, the neutralizing activity is robust in the vast majority of people. “A third dose boosts our defenses, making it harder for the virus to cause severe COVID-19.”
David LV Bauer, group leader at the Crick’s RNA Virus Replication Laboratory and member of the G2P-UK National Virology Consortium, said: "While the Omicron variant has many more mutations than other recent variants, such as Alpha and Delta, “Our data show that the boosters push our immune system to generate a broad response capable of dealing with it.”
Bryan Williams, Director of Research at UCLH, said: “This research shows the power of the partnership between the Crick and the NHS, through our NIHR Biomedical Research Centre. “In addition to these key vaccine efficacy data, we have some really important early data that suggests that at least some versions of the synthetic antibodies that we currently use to treat certain patients are likely effective against this new variant.”
Charles Swanton, principal investigator of Legacy at the Crick and consultant oncologist at UCLH, said: “Our results are an estimate of protection in the community and, as boosters are rolled out at record speeds, many can be confident in their level of protection.” of the vaccine after three doses.”
Sonia Gandhi, principal investigator of Legacy at the Crick and consultant neurologist at UCLH, said: “Now that we have established that boosters are effective against the Omicron variant, future research will need to address the duration and persistence of this booster response. “New variants of concern will continue to emerge as the pandemic evolves, so effective immune monitoring is needed to remain responsive and protected.”
In summary , our results show that two vaccine doses, of AZD1222 in particular, are insufficient to generate a strong response against omicron. Participants who experienced a COVID-19 infection before or after two-dose vaccination generated higher NAbT than those who did not experience a COVID-19 infection, as did those who received a third dose of BNT162b2, which produced NAbT constantly high against omicron (and alpha and delta).
These findings have two important implications.
First, they suggest that available vaccines encoding the ancestral spike protein first detected in Wuhan, China, still induce a NAb response against omicron that is equivalent to that induced by infection with other recent VOCs. This is supported by considerations of the antigenic distance between ancestral peaks and VOCs.
Second, while each spike variant appears to induce the highest NAbT itself with a defined hierarchy of cross-reactivity, we observed that the difference in cross-recognition of heterologous spikes is substantially reduced after booster vaccination, online with recent reports.
It will be important to dissect the characteristics driving this broad response in various cohorts (vaccine type, prior infection, age, comorbidities) as future booster vaccination strategies are considered.
| To conclude , the results from our cohort of healthy working-age adults support a three-dose COVID-19 vaccination strategy for the general population, and the broad neutralizing response observed suggests urgent global action to administer three-dose vaccination. dose could increase the population. immunity against current VOCs (including omicron) and helps prevent the emergence of new variants. |
