hybrid immunity protects against Omicron reinfections

In a recent study published on Research Square*preprint server, researchers assessed the impact of immune fingerprinting of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Wuhan-Hu-1 (WH1) strain on immunological responses based on antibodies (humoral) against antigenically distinct SARS-CoV-2 Subvariant Omicron BF.7.

Study: Humoral immune response to omicron infection in long-term Wuhan-Hu-1 imprinted population. Image Credit: AndriiVodolazhskyi/Shutterstock.com

*Important Notice: Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice/health-related behaviors, or treated as established information.

Background

At this time, the World Health Organization (WHO) does not advocate SARS-CoV-2 vaccinations after the initial booster dose in people at low risk due to high levels of hybrid immunity against generalized Omicron infections and coronavirus disease 2019 (COVID-19) vaccines.

Natural infection provides long-lasting immune protection against reinfection; however, this can lead to immunological fingerprinting, biasing immunological responses towards the initially exposed SARS-CoV-2 antigenaccording to antigenic distances.

About the study

The present study investigated whether prior WH1 infection and WH1-based vaccinations could prevent reinfections with Omicron.

Among people infected with Wuhan-Hu-1 from Xiangyang, Omicron infections confirmed by rapid antigen test or polymerase chain reaction (PCR) were detected in 54 out of 60 people who responded to the survey in January 2023, of which 42 people provided blood samples after two months of reinfection with Omicron.

Five people, 20 people, and 17 people were one-dose, two-dose, and three-dose whole-type inactivated virus (WIV) vaccinates who had received the vaccines between the Wihan-Hu-1 strain and Omicron variant infections, respectively.

Additionally, 13 blood samples from triply vaccinated and WH1-infected individuals were obtained three to four months prior to Omicron infection as individuals in the pre-Omicron infection control group.

Additionally, three groups of individuals residing in the same locality but with a negative pre-Omicron SARS-CoV-2 infection history were analyzed. Blood samples were collected before and after Omicron infections from healthcare providers who had received three doses of WIV vaccines (BBIBP-CorV, WIBP-CorV or CoronaVac) or the ZF2001RBD subunit vaccine and formed the vaccinated-only cohorts.

Blood samples were also obtained after Omicron infection from unvaccinated individuals with no history of SARS-CoV-2 infection prior to Omicron infection who formed the naïve control group. None of the participants suffered from immune system disorders or took immune-modifying drugs.

Humoral immunity was assessed by neutralization assays involving vesicular stomatitis virus pseudotyped with SARS-CoV-2 spike (S) proteins from strain Wuhan-Hu-1 and subvariants BF.7 , XBB.1.5 and BQ.1.1 from Omicron.

A chemiluminescent microparticle immunoassay (CMIA) in vitro diagnostic tool (IVD) was used to quantify anti-WH1 receptor binding domain (RBD) antibodies.

Results

The hybrid and vaccine-only imprint increased post-infection WH1 and Omicron BF.7/BQ.1.1/XBB.1.5 serological neutralization more than the naïve background.

Feedback from preexisting high-affinity antibodies limited humoral responses to Omicron infection without compromising protection. In contrast, the antigenic antiquity of pre-existing cross-reacting B cells slightly decreased the extent of direct neutralization in individuals imprinted with hybrid and RBD vaccines.

Neutralization titers obtained after Omicron infections have been correlated with antibody-based immunity against reinfection. Higher titers of Wuhan-Hu-1 neutralization were noted in individuals with prior immunological memory of Wuhan-Hu-1, regardless of imprint type.

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

Hybrid imprinted individuals had comparable WH1 and Omicron titers regardless of vaccinations. Individuals infected with ZF2001 and WH1 and vaccinated with WIV (hyrbid3) vaccines with higher pre-infection Wuhan-Hu-1 titers demonstrated lower fold elevations in Wuhan-Hu-1 titers compared to post-infection WIV vaccinates. Omicron infection.

Similarly, fold increases in titers against BF.7 were inversely correlated with this pre-infection, and the hybrid3 group showed lower fold increases in titers against XBB.1.5 and BQ.1.1 compared to WIV vaccine recipients. .

Highly imprinted individuals with durable hybrid immune protection or Wuhan-Hu-1 RBD vaccinates exhibited high anti-Wuhan-Hu-1 titers. Humoral feedback may have masked the limited epitopes shared between Wuhan-Hu-1 and Omicron after Omicron infection.

Wuhan-Hu-1 NT/Ac ratios (WH1 titers/anti-Wuhan-Hu-1 RBD antibodies) were reduced for imprinted individuals despite a considerable increase in Ac titers following infection with Omicron, and the decrease in the ratio NT/Ac was inversely associated with Wuhan-Hu-1 titers before infection.

Homologous vaccinations following Wuhan-Hu-1 infections increased Wuhan-Hu-1 NT/Ab values, while Omicron infections did not. ZF2001 and WIV vaccinees showed non-significant differences in XBB.1.5 subvariant/BF.7 subvariant and BQ.1.1 subvariant/BF.7 subvariant ratios after infection compared to naïve individuals .

Of note, hybrid imprinted individuals with higher pre-infection BF.7 subvariant titers and BF.7/Wuhan-Hu-1 subvariant ratios showed XBB subvariant ratios. 1.5/BF.7 slightly lower compared to individuals with vaccine imprint.

Post-infection samples with anti-Wuhan-Hu-1 RBD titers neutralized Wuhan-Hu-1 and pre-infection samples from WIV vaccinates. ZF2001 vaccinees showed a greater decrease in Wuhan-Hu-1 NT/Ab values ​​after infection compared to WIV vaccinees.

Furthermore, the absence of other RBD B cells before infection among ZF2001 vaccinees generated more effective B cell repertoires against the XBB.1.5 subvariant than the BQ.1.1 subvariant post-infection, which which differed from observations in WIV vaccinates, indicating that additional RBD epitopes contributed to immunologic fingerprinting.

Conclusion

Overall, the study results demonstrated the efficacy of hybrid immunity against Omicron reinfection in individuals with long-term immune imprinting.

*Important Notice: Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice/health-related behaviors, or treated as established information.