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Three-dose vaccination-induced immune responses protect against SARS-CoV-2 Omicron BA.2
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  • Runhong Zhou,
  • Na Liu,
  • Xin Li,
  • Qiaoli Peng,
  • Cheuk-Kwan Yiu,
  • Haode Huang,
  • Dawei Yang,
  • Zhenglong Du,
  • Hau-Yee Kwok,
  • Ka-Kit Au,
  • Jian-Piao Cai,
  • Ivan Fan-Ngai Hung,
  • Kelvin KW,
  • Xiaoning Xu,
  • Kwok-Yung Yuen,
  • Zhiwei Chen
Runhong Zhou
The University of Hong Kong Li Ka Shing Faculty of Medicine

Corresponding Author:zhourh@hku.hk

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Na Liu
The University of Hong Kong Li Ka Shing Faculty of Medicine
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Xin Li
The University of Hong Kong Li Ka Shing Faculty of Medicine
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Qiaoli Peng
The University of Hong Kong Li Ka Shing Faculty of Medicine
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Cheuk-Kwan Yiu
The University of Hong Kong Li Ka Shing Faculty of Medicine
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Haode Huang
The University of Hong Kong Li Ka Shing Faculty of Medicine
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Dawei Yang
The University of Hong Kong Li Ka Shing Faculty of Medicine
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Zhenglong Du
The University of Hong Kong Li Ka Shing Faculty of Medicine
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Hau-Yee Kwok
The University of Hong Kong Li Ka Shing Faculty of Medicine
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Ka-Kit Au
The University of Hong Kong Li Ka Shing Faculty of Medicine
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Jian-Piao Cai
The University of Hong Kong Li Ka Shing Faculty of Medicine
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Ivan Fan-Ngai Hung
The University of Hong Kong Li Ka Shing Faculty of Medicine
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Kelvin KW
The University of Hong Kong Li Ka Shing Faculty of Medicine
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Xiaoning Xu
Imperial College London
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Kwok-Yung Yuen
The University of Hong Kong Li Ka Shing Faculty of Medicine
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Zhiwei Chen
The University of Hong Kong Li Ka Shing Faculty of Medicine
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Abstract

Background: The ongoing outbreak of SARS-CoV-2 Omicron BA.2 infections in Hong Kong, the world model city of universal masking, has resulted in a major public health crisis. Although the third heterologous BNT162b2 vaccination after 2-dose CoronaVac generated higher neutralizing antibody responses than the third homologous CoronaVac booster, vaccine efficacy and corelates of immune protection against the major circulating Omicron BA.2 remains to be investigated. Methods: We investigated the vaccine efficacy against the Omicron BA.2 breakthrough infection among 481 public servants who had been received with SARS-CoV-2 vaccines including two-dose BNT162b2 (2×BNT, n=169), three-dose BNT162b2 (2×BNT, n=175), two-dose CoronaVac (2×CorV, n=37), three-dose CoronaVac (3×CorV, n=68) and third-dose BNT162b2 following 2×CorV (2×CorV+1BNT, n=32). Humoral and cellular immune responses after three-dose vaccination were characterized and correlated with clinical characteristics of BA.2 infection. Results: During the BA.2 outbreak, 29.3% vaccinees were infected. Three-dose vaccination provided protection with lower incidence rates of breakthrough infections (2×BNT 49.2% vs 3×BNT 16.6%, p<0.0001; 2×CorV 48.6% vs 3×CoV 20.6%, p=0.003). The third heterologous vaccination showed the lowest incidence (2×CorV+1×BNT 6.3%). Although BA.2 conferred the highest neutralization resistance compared with variants of concern tested, the third dose vaccination-activated spike-specific memory B and Omicron cross-reactive T cell responses contributed to reduced frequencies of breakthrough infection and disease severity. Conclusions: Our results have implications to timely boost vaccination and immune responses likely required for vaccine-mediated protection against Omicron BA.2 pandemic.
Published in SSRN Electronic Journal. 10.2139/ssrn.4123263