Can human antibody defense withstand the impact of SARS-CoV-2 variants?

[Catalina GarciaParticipant]

On May 18, 2022, a research team from the University of California, San Francisco and the affiliated Gladstone Institutes published in Nature a study entitled “Limited cross-variant immunity from SARS-CoV-2 Omicron without vaccination”. The study found that in unvaccinated individuals, natural immunity acquired through infection with Omicron did not provide long-term immunity to other variants, while individuals who were vaccinated and then infected with Omicron were able to develop immunity to other variants.

Delta and Omicron are the new coronavirus variants of concern (VOC). Individuals infected with Delta are at risk of developing severe lung disease, while individuals infected with Omicron typically have only mild symptoms, especially in vaccinated ones. So, the question arises: how effective is the immunity induced by Omicron in infecting a large population? Is there cross-protection against future variants? The answers to these questions will have important implications for public health strategies.

The study was designed to address these questions.
* Use a collection of wild-type SARS-CoV-2 (WA1), Delta and Omicron, and intranasally infected transgenic mice overexpressing human ACE2. The researchers monitored the body temperature and body weight of the test mice over the following 7 days as an indicator of disease progression.
* Quantify the production of infectious particles and viral RNA expression in the respiratory tract and lungs of infected mice over time to assess viral replication kinetics.
* Detect pro-inflammatory marker levels and T cell phenotype in mice to assess Omicron pathogenicity.
* Collect mouse sera and detect neutralization efficiency against the virus and measurement of humoral immune response.
* Collect serum samples from adults (18-50 years old) in clinical trials who had been vaccinated and those who had not been vaccinated but both had a history of COVID-19 to investigate immune escape from the SARS-CoV-2 variants.

Results showed that:
* Omicron’s weak ability to cause severe disease is related to its low replication and induced antibody type
Omicron infection was found to be significantly milder in mice infected with Omicron and to produce a lower immune response than WA1 and Delta infections. Despite the milder symptoms caused by Omicron, the mice’s immune system still produced T cells and antibodies. In addition, low replication of Omicron was detected in mouse respiratory cells, and again, Omicron was able to infect human cells, but at significantly lower replication levels than the other variants.

* Antibodies obtained from Omicron infection do not effectively neutralize other mutant strains
In vaccinated populations, when their immune systems are exposed to Omicron or Delta “breakthrough infections”, existing immunity can be boosted by mobilizing “mixed immunity” against all variants and by providing broad-spectrum protection against the infection.

Dr. Melanie Ott, director of the Gladstone Institute of Virology and an author of the study, said, “In the unvaccinated population, immunity from Omicron infection may be equivalent to a single vaccination, which provides protection against new coronavirus infections, but it’s not very broad. When it comes to other variants that may evolve in the future, we cannot predict exactly what will happen, but based on this result, I suspect that unvaccinated people infected with Omicron have little protection. In contrast, vaccinated individuals may be more broadly protected, especially from future variants when faced with breakthrough infections.”

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