The study findings, titled “Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination,” were published in Nature by a team of researchers from the University of California, San Francisco, and the affiliated Gladstone Institute. It was discovered that natural immunity established by infection with Omicron did not provide long-term immunity to other variants among individuals without vaccination, while vaccinated individuals infected with Omicron might develop immunity to other variants.
Delta and Omicron are globally relevant variants of concern (VOC). Although individuals infected with Delta are at risk of developing severe lung disease, infected with Omicron often causes milder symptoms, especially in vaccinated individuals. The questions of whether the widespread Omicron can provide an effective immune response and if it can contribute to future cross-variant protection are raised, and the answers will have a crucial impact on public health strategies.
To answer these questions, the researchers first intranasally infected transgenic mice overexpressing human ACE2 (Angiotensin-Converting Enzyme 2) with the three collected wild-type novel coronaviruses (WA1), Delta, and Omicron, and monitored the indicators of the mice over 7 days. And they collected serum samples from adults (aged 18 to 50) who had been vaccinated against COVID-19 and from those who had not but were infected with COVID-19 in clinical trials to investigate immune escape from the COVID-19 variant. It was found that:
- Omicron-infected mice with mild symptom is related to its low replication and induced antibody type.
It was found that Omicron-infected mice had significantly milder symptoms, and the immune response was lower than that of WA1 and Delta infections. Although with the mild symptoms, the mouse immune system still generates T cells and antibodies. In addition, Omicron replication was found to be low in mouse respiratory tract cells. Omicron could also infect human cells, but its replication was significantly lower than that of other variants. The low replication of Omicron and the type of antibodies produced by the immune system in response to the virus may explain why Omicron differs from other variants in terms of symptoms and immunity.
- The antibodies produced by Omicron infection can not effectively neutralize other mutant strains.
To track the development of Omicron’s immune response over time, the researchers collected blood samples from mice infected with variants of WA1, Delta, and Omicron, and measured the ability of their immune cells and antibodies to recognize five different viruses (WA1, Alpha, Beta, Delta, and Omicron).
Antibodies produced by mice-infected WA1 can neutralize Alpha, and to a lesser extent, Beta and Delta, but not Omicron. Antibodies produced by mice-infected Delta can neutralize WA1, Alpha, and to a lesser extent, Omicron and Beta. The antibodies produced by Omicron infection, however, are only capable of neutralizing Omicron variants and are useless against other variants of novel coronavirus.
While 10 unvaccinated individuals infected with Omicron are unable to neutralize other variants, 11 unvaccinated individuals infected with Delta can do so to a lesser extent. When faced with breakthrough infections with either Omicron or Delta, vaccinated individuals can neutralize all tested variants, gaining higher protection.
The results show that when the immune system of vaccinated individuals encounters Omicron or Delta “breakthrough infection,” it can enhance the existing immunity by mobilizing “mixed immunity” against all mutants and providing broad-spectrum protection against infection. Based on the current data, the researchers predict that vaccinated individuals will be better protected against Omicron infections or future variants.
Dr. Melanie Ott, director of the Gladstone Institute of Virology and author of the study, indicated that “the immunity from Omicron infection in unvaccinated people may be equivalent to a shot of the vaccine, which protects against novel coronavirus infection with a small scope. However, we cannot accurately predict the outcomes for other variants that may develop in the future. Based on this result, however, I suspect that unvaccinated individuals infected with Omicron have little defense. Contrarily, those who have been vaccinated may be better protected, especially in the face of a breakthrough infection from the future COVID-19 mutant virus.”