Characterizing fitness and immune escape of SARS-CoV-2 EG.5 sublineage using elderly serum and nasal organoid

Xiaojuan Zhang; Stephanie Joy-Ann Lam; Jonathan Daniel Ip; Carol Ho-Yan Fong; Allen Wing-Ho Chu; Wan-Mui Chan; Yoyo Suet-Yiu Lai; Hoi-Wah Tsoi; Brian Pui-Chun Chan; Lin-Lei Chen; Xinjie Meng; Shuofeng Yuan; Hanjun Zhao; Vincent Chi-Chung Cheng; Jacqueline Kwan Yuk Yuen; Kwok-Yung Yuen; Jie Zhou; Kelvin Kai-Wang To

doi:10.1016/j.isci.2024.109706

Characterizing fitness and immune escape of SARS-CoV-2 EG.5 sublineage using elderly serum and nasal organoid

iScience. 2024 Apr 9;27(5):109706. doi: 10.1016/j.isci.2024.109706. eCollection 2024 May 17.

Authors

Xiaojuan Zhang¹, Stephanie Joy-Ann Lam^{1

2}, Jonathan Daniel Ip¹, Carol Ho-Yan Fong^{1

2}, Allen Wing-Ho Chu^{1

2}, Wan-Mui Chan¹, Yoyo Suet-Yiu Lai^{1

2}, Hoi-Wah Tsoi¹, Brian Pui-Chun Chan¹, Lin-Lei Chen^{1

2}, Xinjie Meng¹, Shuofeng Yuan^{1

2}, Hanjun Zhao^{1

2}, Vincent Chi-Chung Cheng^{1

3}, Jacqueline Kwan Yuk Yuen⁴, Kwok-Yung Yuen^{1

2

3

5}, Jie Zhou^{1

2}, Kelvin Kai-Wang To^{1

2

3

5}

Affiliations

¹ State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
² Centre for Virology, Vaccinology and Therapeutics, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China.
³ Department of Microbiology, Queen Mary Hospital, Pokfulam, Hong Kong Special Administrative Region, China.
⁴ Division of Geriatric Medicine, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
⁵ Department of Infectious Disease and Microbiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.

Abstract

SARS-CoV-2 Omicron variant has evolved into sublineages. Here, we compared the neutralization susceptibility and viral fitness of EG.5.1 and XBB.1.9.1. Serum neutralization antibody titer against EG.5.1 was 1.71-fold lower than that for XBB.1.9.1. However, there was no significant difference in virus replication between EG.5.1 and XBB.1.9.1 in human nasal organoids and TMPRSS2/ACE2 over-expressing A549 cells. No significant difference was observed in competitive fitness and cytokine/chemokine response between EG.5.1 and XBB.1.9.1. Both EG.5.1 and XBB.1.9.1 replicated more robustly in the nasal organoid from a younger adult than that from an older adult. Our findings suggest that enhanced immune escape contributes to the dominance of EG.5.1 over earlier sublineages. The combination of population serum susceptibility testing and viral fitness evaluation with nasal organoids may hold promise in risk assessment of upcoming variants. Utilization of serum specimens and nasal organoid derived from older adults provides a targeted risk assessment for this vulnerable population.

Keywords: Immune response; Immunology; Virology.