In a recent study posted to the Research Square* preprint server, researchers evaluated the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Wuhan-Hu-1 strain (WH1) immune imprinting on antibody-based (humoral) immunological responses against the antigenically distinct SARS-CoV-2 Omicron BF.7 subvariant.

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*Important notice: Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

At present, the World Health Organization (WHO) does not advocate SARS-CoV-2 vaccinations after the initial booster dose among low-risk individuals due to high levels of hybrid immunity from widespread Omicron infections and coronavirus disease 2019 (COVID-19) vaccines.

Natural infection provides durable immune protection against reinfections; however, it may lead to immunological imprinting, skewing immunological responses toward the initially exposed SARS-CoV-2 antigen, depending on the antigenic distances.

About the study

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

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

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

In addition, 13 blood samples from triple-vaccinated and WH1-infected individuals were obtained three to four months before the Omicron infection as pre-Omicron infection control group individuals.

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

Blood samples were also obtained after the Omicron infection from unvaccinated individuals without SARS-CoV-2 infection history before the Omicron infection who formed the naive control group. No participant suffered from immune system disorders or took immune system-altering medications.

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

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

Results

Hybrid and vaccine-only imprinting augmented post-infection serological WH1 and Omicron BF.7/BQ.1.1/XBB.1.5 neutralization more than naive backgrounds.

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

Neutralization titers obtained after Omicron infections were 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, irrespective of the type of imprinting.

Hybrid immune imprinting induced higher titers against BF.7 than WIV imprinting and the naive background. Forward protection was better among hybrid-imprinted individuals than WIV vaccinees and naive individuals.

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

Likewise, fold increases in titers against BF.7 were inversely correlated with that 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.

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

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

Homologous vaccinations following Wuhan-Hu-1 infections increased the Wuhan-Hu-1 NT/Ab values contrasting Omicron infections. 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 post-infection compared to naive individuals.

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

Post-infection samples with anti-Wuhan-Hu-1 RBD titers neutralized Wuhan-Hu-1 and pre-infection samples of WIV vaccinees. ZF2001 vaccinees showed a larger decrease in the Wuhan-Hu-1 NT/Ab values post-infection compared to WIV vaccinees.

Further, the lack of other RBD B lymphocytes pre-infection among ZF2001 vaccinees generated more effective B lymphocyte repertoires against the XBB.1.5 subvariant than the BQ.1.1 subvariant post-infection, which differed from observations among WIV vaccinees, indicating that additional RBD epitopes contributed to immunological imprinting.

Conclusion

Overall, the study findings highlighted the effectiveness of hybrid immunity against Omicron reinfection among long-term immune-imprinted individuals.

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

Written by

Pooja Toshniwal Paharia

Dr. based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.