Waning immune responses against SARS-CoV-2 variants of concern among vaccinees in Hong Kong

Qiaoli Peng; Runhong Zhou; Yuewen Wang; Meiqing Zhao; Na Liu; Shuang Li; Haode Huang; Dawei Yang; Ka-Kit Au; Hui Wang; Kwan Man; Kwok-Yung Yuen; Zhiwei Chen

doi:10.1016/j.ebiom.2022.103904

Waning immune responses against SARS-CoV-2 variants of concern among vaccinees in Hong Kong

EBioMedicine. 2022 Mar:77:103904. doi: 10.1016/j.ebiom.2022.103904. Epub 2022 Mar 3.

Authors

Qiaoli Peng¹, Runhong Zhou², Yuewen Wang³, Meiqing Zhao², Na Liu², Shuang Li², Haode Huang², Dawei Yang², Ka-Kit Au², Hui Wang⁴, Kwan Man³, Kwok-Yung Yuen⁵, Zhiwei Chen⁶

Affiliations

¹ AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong. Hong Kong Special Administrative Region, People's Republic of China; National Clinical Research Center for Infectious Diseases, HKU AIDS Institute Shenzhen Research laboratory, The Third People's Hospital of Shenzhen and The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, People's Republic of China.
² AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong. Hong Kong Special Administrative Region, People's Republic of China.
³ Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
⁴ National Clinical Research Center for Infectious Diseases, HKU AIDS Institute Shenzhen Research laboratory, The Third People's Hospital of Shenzhen and The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, People's Republic of China.
⁵ AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong. Hong Kong Special Administrative Region, People's Republic of China; State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China; Centre for Virology, Vaccinology and Therapeutics Limited, The University of Hong Kong, Hong Kong Special Administrative Region, China.
⁶ AIDS Institute, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China; Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong. Hong Kong Special Administrative Region, People's Republic of China; National Clinical Research Center for Infectious Diseases, HKU AIDS Institute Shenzhen Research laboratory, The Third People's Hospital of Shenzhen and The Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, People's Republic of China; State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Hong Kong Special Administrative Region, People's Republic of China; Centre for Virology, Vaccinology and Therapeutics Limited, The University of Hong Kong, Hong Kong Special Administrative Region, China. Electronic address: zchenai@hku.hk.

Abstract

Background: Nearly 4 billion doses of the BNT162b2-mRNA and CoronaVac-inactivated vaccines have been administrated globally, yet different vaccine-induced immunity against SARS-CoV-2 variants of concern (VOCs) remain incompletely investigated.

Methods: We compare the immunogenicity and durability of these two vaccines among fully vaccinated Hong Kong people.

Findings: Standard BNT162b2 and CoronaVac vaccinations were tolerated and induced neutralizing antibody (NAb) (100% and 85.7%) and spike-specific CD4 T cell responses (96.7% and 82.1%), respectively. The geometric mean NAb IC₅₀ and median frequencies of reactive CD4 subsets were consistently lower among CoronaVac-vaccinees than BNT162b2-vaccinees. CoronaVac did not induce measurable levels of nucleocapsid protein-specific IFN-γ⁺ CD4⁺ T or IFN-γ⁺ CD8⁺ T cells compared with unvaccinated. Against VOCs, NAb response rates and geometric mean IC₅₀ titers against B.1.617.2 (Delta) and B.1.1.529 (Omicron) were significantly lower for CoronaVac (50%, 23.2 and 7.1%, <20) than BNT162b2 (94.1%, 131 and 58.8%, 35.0), respectively. Three months after vaccinations, NAbs to VOCs dropped near to detection limit, along with waning memory T cell responses, mainly among CoronaVac-vaccinees.

Interpretation: Our results indicate that vaccinees especially CoronaVac-vaccinees with significantly reduced NAbs may probably face higher risk to pandemic VOCs breakthrough infection.

Funding: This study was supported by the Hong Kong Research Grants Council Collaborative Research Fund (C7156-20GF and C1134-20GF); the Wellcome Trust (P86433); the National Program on Key Research Project of China (Grant 2020YFC0860600, 2020YFA0707500 and 2020YFA0707504); Shenzhen Science and Technology Program (JSGG20200225151410198 and JCYJ20210324131610027); HKU Development Fund and LKS Faculty of Medicine Matching Fund to AIDS Institute; Hong Kong Innovation and Technology Fund, Innovation and Technology Commission and generous donation from the Friends of Hope Education Fund. Z.C.'s team was also partly supported by the Theme-Based Research Scheme (T11-706/18-N).

Keywords: Cellular immune response; Humoral immune response; Inactivated vaccine; SARS-CoV-2; mRNA vaccine.

MeSH terms

Antibodies, Neutralizing
Antibodies, Viral
BNT162 Vaccine
CD8-Positive T-Lymphocytes
COVID-19* / epidemiology
COVID-19* / prevention & control
Hong Kong / epidemiology
Humans
Immunity
SARS-CoV-2* / genetics
Vaccination

Substances

Antibodies, Neutralizing
Antibodies, Viral
BNT162 Vaccine

Supplementary concepts

SARS-CoV-2 variants