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Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause severe disease.

ABSTRACT: Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against coronaviruses that cause severe disease, for anticipating novel pandemic-causing viruses, and to respond more effectively to SARS-CoV-2 variants. The emergence of the Omicron variant of SARS-CoV-2 has illustrated the limitations of solely targeting the receptor binding domain (RBD) of the envelope Spike (S)-protein. Here, we isolated a large panel of broadly neutralizing antibodies (bnAbs) from SARS-CoV-2 recovered-vaccinated donors that target a conserved S2 region in the fusion machinery on betacoronavirus spikes. Select bnAbs show broad in vivo protection against all three pathogenic betacoronaviruses, SARS-CoV-1, SARS-CoV-2 and MERS-CoV, that have spilled over into humans in the past 20 years to cause severe disease. The bnAbs provide new opportunities for antibody-based interventions and key insights for developing pan-betacoronavirus vaccines.

SUBMITTER: Zhou P

PROVIDER: S-EPMC8923106 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause severe disease.

Zhou Panpan P Song Ge G He Wan-Ting WT Beutler Nathan N Tse Longping V LV Martinez David R DR Schäfer Alexandra A Anzanello Fabio F Yong Peter P Peng Linghang L Dueker Katharina K Musharrafieh Rami R Callaghan Sean S Capozzola Tazio T Yuan Meng M Liu Hejun H Limbo Oliver O Parren Mara M Garcia Elijah E Rawlings Stephen A SA Smith Davey M DM Nemazee David D Jardine Joseph G JG Wilson Ian A IA Safonova Yana Y Rogers Thomas F TF Baric Ralph S RS Gralinski Lisa E LE Burton Dennis R DR Andrabi Raiees R

bioRxiv : the preprint server for biology 20220307

Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against coronaviruses that cause severe disease, for anticipating novel pandemic-causing viruses, and to respond more effectively to SARS-CoV-2 variants. The emergence of the Omicron variant of SARS-CoV-2 has illustrated the limitations of solely targeting the receptor binding domain (RBD) of the envelope Spike (S)-protein. Here, we isolated a large panel of broadly neutralizing antibodies (bnA ...[more]

PMID: 35291291

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Project description:Novel therapeutic and preventive strategies are needed to contain the HIV-1 epidemic. Broadly neutralizing human antibodies (bNAbs) with exceptional activity against HIV-1 are currently being tested in HIV-1 prevention trials. The selection of anti-HIV-1 bNAbs for clinical development was primarily guided by their in vitro neutralizing activity against HIV-1 Env pseudotyped viruses. Here we report on the neutralizing activity of 9 anti-HIV-1 bNAbs now in clinical development against 126 Clade A, C, D PBMC-derived primary African isolates. The neutralizing potency and breadth of the bNAbs tested was significantly reduced compared to pseudotyped viruses panels. The difference in sensitivity between pseudotyped viruses and primary isolates varied from 3- to nearly 100-fold depending on the bNAb and the HIV-1 clade. Thus, the neutralizing activity of bNAbs against primary African isolates differs from their activity against pseudovirus panels. The data have significant implications for interpreting the results of ongoing HIV-1 prevention trials.IMPORTANCE HIV remains a major public health problem worldwide, and new therapies and preventive strategies are necessary for controlling the epidemic. Broadly neutralizing antibodies (bNAbs) have been developed in the past decade to fill this gap. The neutralizing activity of these antibodies against diverse HIV strains has mostly been measured using Env-pseudotyped viruses, which overestimate bNAb coverage and potency. In this study we measured the neutralizing activity of nine bNAbs against clade A, C, and D HIV isolates derived from cells of African patients living with HIV and produced in peripheral blood mononuclear cells. We found that the coverage and potency of bNAbs were often significantly lower than what was predicted by Env-psuedotyped viruses, and that this decrease was related to the bNAb biding site class. This data is important for the planning and analysis of clinical trials that seek to evaluate bNAbs for the treatment and prevention of HIV infection in Africa.

Dataset Information

Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause severe disease.

Publications

Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause severe disease.

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