tetano
Editor, Senior Moderator
Acta Pharmacol Sin
. 2023 Jan 27;1-9.
doi: 10.1038/s41401-022-01043-w. Online ahead of print.
Long-term passaging of pseudo-typed SARS-CoV-2 reveals the breadth of monoclonal and bispecific antibody cocktails
Hang Ma[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Hui-Fang Zong[SUP] #[/SUP][SUP] 1 2 4 [/SUP], Jun-Jun Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Ya-Li Yue[SUP] #[/SUP][SUP] 1 2 [/SUP], Yong Ke[SUP] 1 2 [/SUP], Yun-Ji Liao[SUP] 1 2 [/SUP], Hao-Neng Tang[SUP] 1 2 [/SUP], Lei Wang[SUP] 1 2 [/SUP], Shu-Sheng Wang[SUP] 5 [/SUP], Yun-Sheng Yuan[SUP] 1 2 [/SUP], Ming-Yuan Wu[SUP] 1 2 [/SUP], Yan-Lin Bian[SUP] 1 2 [/SUP], Bao-Hong Zhang[SUP] 1 2 [/SUP], Hai-Yang Yin[SUP] 1 2 [/SUP], Hua Jiang[SUP] 5 [/SUP], Tao Sun[SUP] 6 7 [/SUP], Lei Han[SUP] 8 [/SUP], Yue-Qing Xie[SUP] 9 [/SUP], Jian-Wei Zhu[SUP] 10 11 [/SUP]
Affiliations
Abstract
The continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses challenges to the effectiveness of neutralizing antibodies. Rational design of antibody cocktails is a realizable approach addressing viral immune evasion. However, evaluating the breadth of antibody cocktails is essential for understanding the development potential. Here, based on a replication competent vesicular stomatitis virus model that incorporates the spike of SARS-CoV-2 (VSV-SARS-CoV-2), we evaluated the breadth of a number of antibody cocktails consisting of monoclonal antibodies and bispecific antibodies by long-term passaging the virus in the presence of the cocktails. Results from over two-month passaging of the virus showed that 9E12 + 10D4 + 2G1 and 7B9-9D11 + 2G1 from these cocktails were highly resistant to random mutation, and there was no breakthrough after 30 rounds of passaging. As a control, antibody REGN10933 was broken through in the third passage. Next generation sequencing was performed and several critical mutations related to viral evasion were identified. These mutations caused a decrease in neutralization efficiency, but the reduced replication rate and ACE2 susceptibility of the mutant virus suggested that they might not have the potential to become epidemic strains. The 9E12 + 10D4 + 2G1 and 7B9-9D11 + 2G1 cocktails that picked from the VSV-SARS-CoV-2 system efficiently neutralized all current variants of concern and variants of interest including the most recent variants Delta and Omicron, as well as SARS-CoV-1. Our results highlight the feasibility of using the VSV-SARS-CoV-2 system to develop SARS-CoV-2 antibody cocktails and provide a reference for the clinical selection of therapeutic strategies to address the mutational escape of SARS-CoV-2.
Keywords: SARS-CoV-2; antibody; neutralization; variant; vesicular stomatitis virus.
. 2023 Jan 27;1-9.
doi: 10.1038/s41401-022-01043-w. Online ahead of print.
Long-term passaging of pseudo-typed SARS-CoV-2 reveals the breadth of monoclonal and bispecific antibody cocktails
Hang Ma[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Hui-Fang Zong[SUP] #[/SUP][SUP] 1 2 4 [/SUP], Jun-Jun Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Ya-Li Yue[SUP] #[/SUP][SUP] 1 2 [/SUP], Yong Ke[SUP] 1 2 [/SUP], Yun-Ji Liao[SUP] 1 2 [/SUP], Hao-Neng Tang[SUP] 1 2 [/SUP], Lei Wang[SUP] 1 2 [/SUP], Shu-Sheng Wang[SUP] 5 [/SUP], Yun-Sheng Yuan[SUP] 1 2 [/SUP], Ming-Yuan Wu[SUP] 1 2 [/SUP], Yan-Lin Bian[SUP] 1 2 [/SUP], Bao-Hong Zhang[SUP] 1 2 [/SUP], Hai-Yang Yin[SUP] 1 2 [/SUP], Hua Jiang[SUP] 5 [/SUP], Tao Sun[SUP] 6 7 [/SUP], Lei Han[SUP] 8 [/SUP], Yue-Qing Xie[SUP] 9 [/SUP], Jian-Wei Zhu[SUP] 10 11 [/SUP]
Affiliations
- PMID: 36707721
- PMCID: PMC9880922
- DOI: 10.1038/s41401-022-01043-w
Abstract
The continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses challenges to the effectiveness of neutralizing antibodies. Rational design of antibody cocktails is a realizable approach addressing viral immune evasion. However, evaluating the breadth of antibody cocktails is essential for understanding the development potential. Here, based on a replication competent vesicular stomatitis virus model that incorporates the spike of SARS-CoV-2 (VSV-SARS-CoV-2), we evaluated the breadth of a number of antibody cocktails consisting of monoclonal antibodies and bispecific antibodies by long-term passaging the virus in the presence of the cocktails. Results from over two-month passaging of the virus showed that 9E12 + 10D4 + 2G1 and 7B9-9D11 + 2G1 from these cocktails were highly resistant to random mutation, and there was no breakthrough after 30 rounds of passaging. As a control, antibody REGN10933 was broken through in the third passage. Next generation sequencing was performed and several critical mutations related to viral evasion were identified. These mutations caused a decrease in neutralization efficiency, but the reduced replication rate and ACE2 susceptibility of the mutant virus suggested that they might not have the potential to become epidemic strains. The 9E12 + 10D4 + 2G1 and 7B9-9D11 + 2G1 cocktails that picked from the VSV-SARS-CoV-2 system efficiently neutralized all current variants of concern and variants of interest including the most recent variants Delta and Omicron, as well as SARS-CoV-1. Our results highlight the feasibility of using the VSV-SARS-CoV-2 system to develop SARS-CoV-2 antibody cocktails and provide a reference for the clinical selection of therapeutic strategies to address the mutational escape of SARS-CoV-2.
Keywords: SARS-CoV-2; antibody; neutralization; variant; vesicular stomatitis virus.