Hybrid immunity prevents Omicron reinfection

In a recent study posted on research square*Preprint server, researchers found that immune imprinting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Wuhan-Hu-1 strain (WH1) showed antigenically distinct antibodies to SARS-CoV- Effects on basal (humoral) immune responses were evaluated. 2 Omicron BF.7 subvariant.

study: Humoral immune response to Omicron infection in a long-term imprinted population of Wuhan-Hu-1. Image credit: AndriiVodolazhskyi/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*Important Notices: research square Publishes preliminary scientific reports that have not been peer-reviewed and should therefore not be considered definitive, to guide clinical practice or health-related actions, or to be treated as established information.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

Currently, the World Health Organization (WHO) recommends that SARS-CoV-2 after primary booster vaccination in low-risk individuals, due to high levels of hybrid immunity from widespread Omicron infections and coronavirus disease 2019 (COVID-19) vaccines. We do not recommend vaccination. .

Natural infection provides durable immune protection against reinfection. However, it can cause immunological imprinting and skew immunological responses to initial exposure to SARS-CoV-2. antigendepending on the antigenic distance.

About research

This study investigated whether prior WH1 infection and WH1-based vaccination could prevent reinfection with Omicron.

Of the 60 Wuhan Hu type 1 patients in Xiangyang who responded to the survey in January 2023, 54 out of 60 had Omicron infection detected by rapid antigen test or polymerase chain reaction (PCR), of which 42 had no information. provided. Blood sample two months after reinfection with Omicron.

Five, 20, and 17 individuals received 1, 2, and 3 doses of whole-inactivated virus (WIV) vaccinated during the period between Wihan-Hu-1 strain and Omicron. I was a vaccineeer. Mutant infections, respectively.

In addition, 13 blood samples were collected from triple-vaccinated and WH1-infected individuals 3-4 months prior to Omicron infection as controls prior to Omicron infection.

In addition, three groups of individuals residing in the same area but with a negative history of SARS-CoV-2 infection prior to Omicron were analyzed. Blood samples were taken before and after Omicron infection from a health care worker who had received her three doses of WIV vaccine (BBIBP-CorV, WIBP-CorV, or CoronaVac) or ZF2001RBD. subunit vaccine and formed a vaccine-only cohort.

Blood samples were also collected after Omicron infection from unvaccinated individuals who had no history of SARS-CoV-2 infection prior to Omicron infection and which constituted an unvaccinated control group. None of the participants had immune system disorders or were taking drugs that alter the immune system.

Humoral immunity is based on vesicular stomatitis virus pseudotyped with the Wuhan-Hu-1 strain SARS-CoV-2 spike (S) protein and Omicron’s BF.7, XBB.1.5, and BQ.1.1 subvariants. was assessed by neutralization assays including

Chemiluminescent microparticle immunoassay (CMIA)-based in vitro Anti-WH1 receptor binding domain (RBD) antibodies were quantified using diagnostic (IVD) tools.

result

Hybrid and vaccine-only imprinting enhanced serological WH1 and Omicron BF.7/BQ.1.1/XBB.1.5 neutralization after infection over naive background.

Feedback from pre-existing high-affinity antibodies limited the humoral response to omicron infection without compromising protection. In contrast, antigenic seniority of pre-existing cross-reactive B lymphocytes slightly decreased forward neutralization width among hybrid and RBD vaccine-imprinted individuals.

Neutralizing titers obtained after Omicron infection correlated with antibody-based immunity against reinfection. Higher Wuhan-Hu-1 neutralization titers were found in individuals with prior immunological memory for Wuhan-Hu-1, regardless of the type of imprinting.

Hybrid immune imprinting induced higher titers against BF.7 than WIV imprinting and naive background. Forward protection was better in hybrid-imprinted individuals than in WIV-vaccinated and unvaccinated individuals.

Hybrid-imprinted individuals showed comparable WH1 and Omicron titers regardless of vaccination. Individuals infected with ZF2001 and WH1 and vaccinated with the WIV vaccine (hyrbid3), who had higher Wuhan-Hu-1 titers prior to infection, compared with WIV-vaccinated individuals post-Omicron infection, were significantly more susceptible to Wuhan-Hu-1 A low rate of increase in titer was demonstrated.

Similarly, the fold increase in titer to BF.7 was inversely related to pre-infection, and the hybrid 3 group had lower fold increase in titer to XBB.1.5 and BQ.1.1 compared to WIV vaccinated individuals.

Individuals heavily imprinted with a sustained hybrid immune defense, or Wuhan-Hu-1 RBD vaccinees, showed elevated anti-Wuhan-Hu-1 titers. Limited epitopes shared between Wuhan-Hu-1 and Omicron after Omicron infection may have been masked by humoral feedback.

The Wuhan-Hu-1 NT/Ab (WH1 titer/anti-Wuhan-Hu-1 RBD antibody) ratio is decreased in imprinted individuals despite a significant increase in Ab titer after Omicron infection. and decreased NT/Ab ratios are inversely associated with pre-infection Wuhan-Hu-1 titers.

Allogeneic vaccination after Wuhan-Hu-1 infection increased Wuhan-Hu-1 NT/Ab levels, in contrast to Omicron infection. ZF2001 and WIV vaccinated individuals had higher ratios of He XBB.1.5 subvariant/BF.7 subvariant and He BQ.1.1 subvariant/BF.7 subvariant after infection compared with untreated individuals. No significant difference was shown.

Of note, hybrid-imprinted individuals with higher pre-infection BF.7 subvariant titers and higher BF.7 subvariant/Wuhan-Hu-1 ratios were more likely to be XBB.1.5 compared to vaccine-imprinted individuals. There was a slight decrease in the subvariant/BF.7 subvariant ratio.

Post-infection samples with anti-Wuhan-Hu-1 RBD titers neutralized pre-infection samples from Wuhan-Hu-1 and WIV vaccinated individuals. ZF2001 vaccinees showed a greater reduction in post-infection Wuhan-Hu-1 NT/Ab values ​​compared with WIV vaccinees.

Moreover, since ZF2001 vaccinees lack other RBD B lymphocytes prior to infection, post-infection B lymphocyte repertoires are more effective against the XBB.1.5 submutant than the BQ.1.1 submutant. generated, which differs from the observation among WIV vaccinees and indicates the presence of additional RBD epitopes. Contributed to immunological imprinting.

Conclusion

Overall, the study results highlighted the efficacy of hybrid immunization against Omicron reinfection in long-term immune-imprinted individuals.

*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.