HKUMed found that robust SARS-CoV-2 infection in nasal turbinate underlies incomplete protection by systemic antibody or vaccine

Researchers at the AIDS Institute, Department of Microbiology and State Key Laboratory of Emerging Infectious Diseases, LKS Faculty of Medicine of The University of Hong Kong (HKUMed), in collaboration with scientists at Tsinghua University and Columbia University, conducted a study for determining site-specific prevention of SARS-CoV-2 in nasal turbinate of Syrian hamsters by investigating systemic human neutralising antibodies (HuNAb) and a spike-based DNA vaccine. The study demonstrated that systemic HuNAb or vaccine failed to fully prevent SARS-CoV-2 infection in the nasal turbinate of the hamsters. Robust SARS-CoV-2 infection in the nasal turbinate may help the virus to evade systemic HuNAb. The original research article has now been published online in one of the world’s leading journals Cell Host & Microbe [link to the publication].

By now, COVID-19 pandemic has led to over 111 million infections and 2.48 million deaths, yet whether or not systemic antibody or vaccine would confer full protection against SARS-CoV-2 transmission and disease remains unclear. In this study, the researchers tested three potent HuNAbs against live SARS-CoV-2 infection in Syrian hamsters. These HuNAbs inhibited SARS-CoV-2 infection by competing with human angiotensin converting enzyme-2 for binding to the viral receptor binding domain (RBD). Prophylactic intraperitoneal or intranasal injection of the individual HuNAb’s or DNA vaccination significantly reduced infection in the lungs but not in the nasal turbinate of the hamsters intranasally challenged with SARS-CoV-2. Although post-virus challenge HuNAb therapy suppressed viral loads and lung damage, robust infection was still observed in the hamsters’ nasal turbinate treated within 1-3 days. These findings demonstrate that while systemic HuNAb suppresses SARS-CoV-2 replication and injury in lungs, robust viral infection in the nasal turbinate may help the virus to evade antibody and therefore contribute to subprotection and reinfection.

“It is important for the public to realise that the presence of high titer of serum neutralising antibody after vaccination or antibody therapy does not fully guarantee the protection of our upper airway from infection by SARS-CoV-2. Thus, in addition to vaccination, mask wearing and hand hygiene should still be complied in order to control the virus from spreading”, said co-corresponding author, Professor Yuen Kwok-yung, Henry Fok Professor in Infectious Diseases and Chair of Infectious Diseases, the Department of Microbiology, HKUMed.

“Several COVID-19 vaccines have been approved for emergency use, yet vaccine-induced protection against asymptomatic SARS-CoV-2 infection remains largely unsuccessful. Our findings of robust viral replication in nasal turbinate outcompeting preventive/therapeutic HuNAb or vaccine-induced HuNAb not only reveal a mechanism underlying the difficulty of full protection against asymptomatic infection but also highlight the importance of COVID-19 mucosal vaccine development,” said Professor Chen Zhiwei, Director of the AIDS Institute, Professor of Department of Microbiology, HKUMed, who led the research.

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