Browsing by Author "Wang, Rui"

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    BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection
    (Springer Nature, 2022-06-17) Cao, Yunlong; Yisimayi, Ayijiang; Jian, Fanchong; Song, Weiliang; Xiao, Tianhe; Wang, Lei; Du, Shuo; Wang, Jing; Li, Qianqian; Chen, Xiaosu; Yu, Yuanling; Wang, Peng; Zhang, Zhiying; Liu, Pulan; An, Ran; Hao, Xiaohua; Wang, Yao; Wang, Jing; Feng, Rui; Sun, Haiyan; Zhao, Lijuan; Zhang, Wen; Zhao, Dong; Zheng, Jiang; Yu, Lingling; Li, Can; Zhang, Na; Wang, Rui; Niu, Xiao; Yang, Sijie; Song, Xuetao; Chai, Yangyang; Hu, Ye; Shi, Yansong; Zheng, Linlin; Li, Zhiqiang; Gu, Qingqing; Shao, Fei; Huang, Weijin; Jin, Ronghua; Shen, Zhongyang; Wang, Youchun; Wang, Xiangxi; Xiao, Junyu; Xie, Xiaoliang Sunney
    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage1. The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA.2.12.1, BA.4 and BA.5 (BA.4 and BA.5 are hereafter referred collectively to as BA.4/BA.5) exhibit similar binding affinities to BA.2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA.2.12.1 and BA.4/BA.5 display increased evasion of neutralizing antibodies compared with BA.2 against plasma from triple-vaccinated individuals or from individuals who developed a BA.1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles2, epitope distribution3 and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA.1 infection. BA.1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA.1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1. Nevertheless, these neutralizing antibodies are largely evaded by BA.2 and BA.4/BA.5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab4 and cilgavimab5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants.
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    Deciphering multiplicity of HIV-1C infection : transmission of closely related multiple viral lineages
    (Public Library of Science, 2016-11-28) Novitsky, Vlad; Moyo, Sikhulile; Wang, Rui; Gaseitsiwe, Simani; Essex, M.
    Background: A single viral variant is transmitted in the majority of HIV infections. However, about 20% of heterosexually transmitted HIV infections are caused by multiple viral variants. Detection of transmitted HIV variants is not trivial, as it involves analysis of multiple viral sequences representing intra-host HIV-1 quasispecies. Methodology: We distinguish two types of multiple virus transmission in HIV infection: (1) HIV transmission from the same source, and (2) transmission from different sources. Viral sequences representing intra-host quasispecies in a longitudinally sampled cohort of 42 individuals with primary HIV-1C infection in Botswana were generated by single-genome amplification and sequencing and spanned the V1C5 region of HIV-1C env gp120. The Maximum Likelihood phylogeny and distribution of pairwise raw distances were assessed at each sampling time point (n = 217; 42 patients; median 5 (IQR: 4–6) time points per patient, range 2–12 time points per patient). Results: Transmission of multiple viral variants from the same source (likely from the partner with established HIV infection) was found in 9 out of 42 individuals (21%; 95 CI 10–37%). HIV super-infection was identified in 2 patients (5%; 95% CI 1–17%) with an estimated rate of 3.9 per 100 person-years. Transmission of multiple viruses combined with HIV super-infection at a later time point was observed in one individual. Conclusions: Multiple HIV lineages transmitted from the same source produce a monophyletic clade in the inferred phylogenetic tree. Such a clade has transiently distinct sub-clusters in the early stage of HIV infection, and follows a predictable evolutionary pathway. Over time, the gap between initially distinct viral lineages fills in and initially distinct sub-clusters converge. Identification of cases with transmission of multiple viral lineages from the same source needs to be taken into account in cross-sectional estimation of HIV recency in epidemiological and population studies