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Immune Imprinting with Ancestral SARS-CoV-2 Strain Induced Potent Neutralizing Activity Against Omicron Sublineages BA.2, BA.2.12.1 and BA.4/5

24 Pages Posted: 1 Sep 2022

See all articles by Xiaojuan Zhang

Xiaojuan Zhang

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases

Lin-Lei Chen

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases

Syed Muhammad Umer Abdullah

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases

Jian-Piao Cai

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases

Anthony Raymond Tam

The University of Hong Kong - Division of Infectious Disease

Wing-Ming Chu

The University of Hong Kong - Division of Infectious Disease

Wan-Mui Chan

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases

Jonathan Daniel Ip

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases

Allen Wing-Ho Chu

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases

Lu Lu

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases

Brain Pui-Chun Chan

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases

Yan Zhao

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases

Kwok-Hung Chan

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases

Kwok-Yung Yuen

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases

Vincent Chi-Chung Cheng

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases

Ivan Fan Ngai Hung

The University of Hong Kong - School of Clinical Medicine

Kelvin Kai-Wang To

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases

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Abstract

Background: Immune imprinting plays a crucial role in subsequent antibody responses against SARS-CoV-2. However, unknown prior exposures due to subclinical infections may confound the results. With a low prevalence of COVID-19 before 2022 (<0.2% of the population), the chance of unknown prior SARS-CoV-2 exposure is low in Hong Kong, which provides a unique opportunity to accurately delineate the importance immune imprinting.

Methods: We determined and compared the neutralizing antibody titer against SARS-CoV-2 ancestral strain and Omicron sublineages for patients with different infection or vaccination exposure history between 2020 and 2022.

Findings: Individuals infected with SARS-CoV-2 ancestral strain in 2020 and boosted with only a single dose of BNT162b2 (2020-infected/1x-BNT162b2) had high serum neutralizing antibody titers against Omicron variant BA.2, BA.2.12.1 and BA.4/5 sublineages. The levels of neutralizing antibody against ancestral or Omicron strains in the 2020-infected/1x-BNT162b2 group were at least 8.6-fold higher than COVID-19-naïve individuals with 2 doses of BNT162b2, and were comparable to the levels seen among groups with 3 exposures to SARS-CoV-2 spike protein by vaccination or infection, including those with Omicron infection. Among patients with Omicron BA.2 infection, those with prior BNT162b2 vaccine had higher neutralization antibody titers against ancestral strain, BA.2 and BA.5 than those with prior CoronaVac.

Interpretation: Our data suggest that imprinting with ancestral strain infection confer robust and broad humoral immune response after subsequent exposures. Patient imprinted with inactivated whole virion COVID-19 vaccines will likely require additional vaccine doses even after Omicron variant infection in order to prevent reinfection with Omicron BA.5 or other upcoming variants.

Funding Information: This work was partly supported by the Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases and Research Capability on Antimicrobial Resistance for Department of Health of the Hong Kong; the Theme-Based Research Scheme [T11/707/15] of the Research Grants Council, Hong Kong Special Administrative Region; Emerging Collaborative Project of Guangzhou Laboratory [EKPG22-01]; and Emergency COVID-19 Project [2021YFC0866100], Major Projects on Public Security, National Key Research and Development Program; and the donations of the Shaw Foundation Hong Kong, Richard Yu and Carol Yu, May Tam Mak Mei Yin, Michael Seak-Kan Tong, Respiratory Viral Research Foundation Limited, Hui Ming, Hui Hoy and Chow Sin Lan Charity Fund Limited, Chan Yin Chuen Memorial Charitable Foundation, and Marina Man-Wai Lee.

Declaration of Interests: KYY, IFHN and KKWT report collaboration with Sinovac and Sinopharm. IFNH received payment from M.S.D. for speaking at the COVID-19 Regional Expert Input Forum 2021; is on the advisory board of Pfizer on COVID-19 management in 2022; and was on the advisory board of Gilead on evolving treatment landscape in COVID-19 in 2021. Other authors declare no competing interests.

Ethics Approval Statement: This study was approved by the institutional review board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (UW 13–265 and UW 21–214) and the Hospital Authority Kowloon West Cluster (KW/EX-20–038[144–26]). Written informed consent was obtained from all study participants.

Keywords: COVID-19, SARS-CoV-2, Omicron variant, BA.2.12.1, BA.4, BA.5 sublineages, immune imprinting, vaccine, neutralizing antibody, hybrid immunity

Suggested Citation

Zhang, Xiaojuan and Chen, Lin-Lei and Abdullah, Syed Muhammad Umer and Cai, Jian-Piao and Tam, Anthony Raymond and Chu, Wing-Ming and Chan, Wan-Mui and Ip, Jonathan Daniel and Chu, Allen Wing-Ho and Lu, Lu and Chan, Brain Pui-Chun and Zhao, Yan and Chan, Kwok-Hung and Yuen, Kwok-Yung and Cheng, Vincent Chi-Chung and Hung, Ivan Fan Ngai and To, Kelvin Kai-Wang, Immune Imprinting with Ancestral SARS-CoV-2 Strain Induced Potent Neutralizing Activity Against Omicron Sublineages BA.2, BA.2.12.1 and BA.4/5. Available at SSRN: https://ssrn.com/abstract=4206824 or http://dx.doi.org/10.2139/ssrn.4206824

Xiaojuan Zhang

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases ( email )

Lin-Lei Chen

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases ( email )

Syed Muhammad Umer Abdullah

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases ( email )

Jian-Piao Cai

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases ( email )

Anthony Raymond Tam

The University of Hong Kong - Division of Infectious Disease ( email )

Wing-Ming Chu

The University of Hong Kong - Division of Infectious Disease ( email )

Wan-Mui Chan

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases ( email )

Jonathan Daniel Ip

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases ( email )

Allen Wing-Ho Chu

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases ( email )

Lu Lu

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases ( email )

Brain Pui-Chun Chan

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases ( email )

Yan Zhao

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases ( email )

Kwok-Hung Chan

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases ( email )

Kwok-Yung Yuen

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases ( email )

Vincent Chi-Chung Cheng

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases ( email )

Ivan Fan Ngai Hung

The University of Hong Kong - School of Clinical Medicine ( email )

Kelvin Kai-Wang To (Contact Author)

The University of Hong Kong - State Key Laboratory of Emerging Infectious Diseases ( email )