Strong protection against Omicron re-infection

To date, the ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has killed more than 6.94 million people worldwide. Lives are being taken.

study: Humoral immune response to Omicron infection in a long-term imprinted population of Wuhan-Hu-1. Image credit: Visualstock / Shutterstock.com

*Important Notices: research square Publishes preliminary scientific reports that have not been peer-reviewed and should therefore not be considered definitive, to guide clinical practice or health-related actions, or to be treated as established information. not.

Background

In contrast to previous recommendations, recent World Health Organization (WHO) guidance indicated that annual additional 2019-nCoV vaccination for low-risk populations is not necessary. This latest WHO guidance has sparked debate about the effectiveness of routine booster vaccinations, especially due to the lack of significant serum neutralization against the SARS-CoV-2 omicron subvariant.

The abrupt withdrawal of the COVID-19 booster recommendation is also due to incomplete evidence for the durability and efficacy of natural infection-induced immune protection against reinfection with novel variants with different antigenic signatures. There is a possibility.

The majority of studies found that previous infection with Wuhan-Hu-1 (WH1), the ancestral strain of SARS-CoV-2, and WH1-based vaccination attenuated the humoral immune response to subsequent Omicron infection. showing. These findings are consistent with immune imprinting in influenza virus infection.

Antigen mapping studies demonstrated that the antigenic distance between SARS-CoV-2 mutants and Omicron submutants was only a 103-fold change in neutralization titer level. Therefore, compared with influenza infection, SARS-CoV-2 infection exhibits a smaller imprinting effect.

Most of the world’s population has been exposed to SARS-CoV-2 antigens through WH1-based vaccines. As a result, new research is currently under consideration. nature portfolio And currently posted research square A preprint server assesses the impact of long-term WH1 imprinting on humoral immune responses to antigenically distant SARS-CoV-2 variants to determine maximal imprinting effects in the current SARS-CoV-2 variant landscape do.

About research

China’s Hubei province, the main epicenter of the world’s first COVID-19 outbreak, has managed to avoid all pre-Omicron variants by implementing strict public health measures. Most people in Hubei received several doses of the WH1-based COVID-19 vaccine. Therefore, the majority of this population was exclusively imprinted with WH1.

In December 2022, Hubei experienced a population-wide outbreak of Omicron, with approximately 90% of the population infected with BF.7 submutants and their derivatives. Scientists used the opportunity of this pandemic to study immune imprinting in reinfected participants.

The study cohort consisted of WH1-infected participants from Xiangyang City, Hubei Province. Study participants reinfected with the Omicron variant provided serum samples two months after infection. Some participants received three doses of whole-inactivated virus (WIV) vaccine.

Serum samples collected from WH1-infected persons and participants who had been vaccinated three times 3–4 months before Omicron infection were used as pre-infection controls.

Other cohorts from the same region were also studied. One cohort included vaccinated participants, while another cohort included unvaccinated participants.

Omicron pre- and post-infection serum samples were obtained from vaccinated and non-vaccinated cohorts. Importantly, all participants had no history of immune disease and were not taking any medications that might affect the immune system.

Humoral immune responses were measured using: pseudo virus Neutralization assays were based on non-replicating vesicular stomatitis virus (VSV) pseudotyped with WH1, Omicron BF.7, BQ.1.1, or XBB.1.5 spike proteins.

research result

In the current study, we measured long-term and long-antigen-distance immune imprinting to the humoral immune system using pre- and post-ommicron sera from a population imprinted with WH1 only. Based on pseudovirus neutralization assays, increased neutralization of her WH1 and Omicron subvariants was observed with WH1 imprinting compared with naive sera.

Mechanistically, antibody feedback limited the magnitude of WH1 backboost through enhanced antibody diversity. Moreover, antigen senescence caused a rapid upregulation of omicron neutralization titers by recalling cross-reactive B cells upon omicron infection.

Only hybrid WH1 imprinting slightly reduced forward neutralization amplitude without affecting overall neutralization titers after Omicron infection.

Importantly, imprinting effects collectively increased the level of protection against reinfection. Therefore, it may be beneficial to support immune imprinting of humoral immunity.

Conclusion

Current research supports WHO recommendations for COVID-19 booster vaccination for low-risk populations. Indeed, research results strongly indicate that omicron infection confers immune protection to imprinted populations.

However, SARS-CoV-2 variants with high antigenic drift are less effective at inducing immune defense, regardless of imprinting status. The efficacy of immunoimprinting depends on the quality and quantity of cross-reactive antibodies.

Taken together, long-term WH1 immune imprinting enhances the humoral immune response to omicron infection with negligible side effects, thereby preventing reinfection. In contrast to the results of previous studies, the present study concluded that immune imprinting is a beneficial mechanism.

*Important Notices: research square Publishes preliminary scientific reports that have not been peer-reviewed and should therefore not be considered definitive, to guide clinical practice or health-related actions, or to be treated as established information. not.