Structural insights into broadly neutralizing antibodies against SARS-CoV-2 elicited by hybrid immunity.

Increasing spread by SARS-CoV-2 Omicron variants challenges existing vaccines and broadly reactive neutralizing antibodies (bNAbs) against COVID-19. Here we determine the diversity, potency, breadth and structural insights of bNAbs derived from memory B cells of BNT162b2-vaccinee after homogeneous Omicron BA.1 breakthrough infection. The infection activates diverse memory B cell clonotypes for generating potent class I/II or III bNAbs with new epitopes mapped to receptor-binding domain (RBD). The top eight bNAbs neutralize wildtype and BA.1 potently but display divergent IgH/IgL sequences and neuralization profiles against other variants of concern (VOCs). Two of them (P2D9 and P3E6) belonging to class III NAbs display comparable potency against BA.4/BA.5, although structural analysis reveals distinct modes of action. P3E6 neutralizes all variants tested through a unique bivalent interaction with two RBDs. Our findings provide new insights into hybrid immunity on BNT162b2-induced diverse memory B cells in response to Omicron breakthrough infection for generating diverse bNAbs with distinct structural basis.

A broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge.

The strikingly high transmissibility and antibody evasion of SARS-CoV-2 Omicron variants have posed great challenges to the efficacy of current vaccines and antibody immunotherapy. Here, we screen 34 BNT162b2-vaccinees and isolate a public broadly neutralizing antibody ZCB11 derived from the IGHV1-58 family. ZCB11 targets viral receptor-binding domain specifically and neutralizes all SARS-CoV-2 variants of concern, especially with great potency against authentic Omicron and Delta variants. Pseudovirus-based mapping of 57 naturally occurred spike mutations or deletions reveals that S371L results in 11-fold neutralization resistance, but it is rescued by compensating mutations in Omicron variants. Cryo-EM analysis demonstrates that ZCB11 heavy chain predominantly interacts with Omicron spike trimer with receptor-binding domain in up conformation blocking ACE2 binding. In addition, prophylactic or therapeutic ZCB11 administration protects lung infection against Omicron viral challenge in golden Syrian hamsters. These results suggest that vaccine-induced ZCB11 is a promising broadly neutralizing antibody for biomedical interventions against pandemic SARS-CoV-2.

Investigating the Self-Reported Health Status of Domestic and Overseas Chinese Populations during the COVID-19 Pandemic.

To control the spread of COVID-19, governments in different countries and regions implemented various types of lockdown and outdoor restrictions. The research aimed to describe and compare the health status of Chinese people both domestically and abroad in this global health crisis. An online questionnaire survey was distributed to Chinese mainland citizens living in Hubei (the lockdown province), outside Hubei, and those living abroad in 2020. A total of 1000 respondents were recruited and reported worse health status compared with Chinese population norms. People living in Hubei reported worse health status than those living outside Hubei but revealed better health status than overseas respondents. It was clear that the pandemic as well as strict lockdown and outdoor restriction policies affected Chinese people's health. It is important for the Chinese government to be aware of the negative impact of such strict policies and to take measures to reduce the panic of society when implementing similar policies in the future. It also implies that governments in other countries should promote social support for those who live far from home and actively call for support for non-discriminatory attitudes toward ethnic minorities.