tetano
Editor, Senior Moderator
Sci Transl Med
. 2022 Jan 25;eabl8124.
doi: 10.1126/scitranslmed.abl8124. Online ahead of print.
The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in non-human primates and has an extended half-life in humans
Yueh-Ming Loo[SUP] 1 [/SUP], Patrick M McTamney[SUP] 1 [/SUP], Rosalinda H Arends[SUP] 2 [/SUP], Michael E Abram[SUP] 3 [/SUP], Anastasia A Aksyuk[SUP] 3 [/SUP], Seme Diallo[SUP] 1 [/SUP], Daniel J Flores[SUP] 1 [/SUP], Elizabeth J Kelly[SUP] 3 [/SUP], Kuishu Ren[SUP] 1 [/SUP], Richard Roque[SUP] 1 [/SUP], Kim Rosenthal[SUP] 1 [/SUP], Katie Streicher[SUP] 3 [/SUP], Kevin M Tuffy[SUP] 3 [/SUP], Nicholas J Bond[SUP] 4 [/SUP], Owen Cornwell[SUP] 4 [/SUP], Jerome Bouquet[SUP] 5 [/SUP], Lily I Cheng[SUP] 6 [/SUP], James Dunyak[SUP] 7 [/SUP], Yue Huang[SUP] 5 [/SUP], Anton I Rosenbaum[SUP] 5 [/SUP], Venkatesh Pilla Reddy[SUP] 8 [/SUP], Hanne Andersen[SUP] 9 [/SUP], Robert H Carnahan[SUP] 10 11 [/SUP], James E Crowe Jr[SUP] 10 11 12 [/SUP], Ana I Kuehne[SUP] 13 [/SUP], Andrew S Herbert[SUP] 13 [/SUP], John M Dye[SUP] 13 [/SUP], Helen Bright[SUP] 1 [/SUP], Nicole L Kallewaard[SUP] 1 [/SUP], Menelas N Pangalos[SUP] 14 [/SUP], Mark T Esser[SUP] 15 [/SUP]
Affiliations
Abstract
Despite the success of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, there remains a need for more prevention and treatment options for individuals remaining at risk of coronavirus disease 2019 (COVID-19). Monoclonal antibodies (mAbs) against the viral spike protein have potential to both prevent and treat COVID-19, and reduce the risk of severe disease and death. Here, we describe AZD7442, a combination of two mAbs, AZD8895 (tixagevimab) and AZD1061 (cilgavimab), that simultaneously bind to distinct, nonoverlapping epitopes on the spike protein receptor binding domain to neutralize SARS-CoV-2. Initially isolated from individuals with prior SARS-CoV-2 infection, the two mAbs were designed to extend their half-lives and reduce effector functions. The AZD7442 mAbs individually prevent the spike protein from binding to angiotensin-converting enzyme 2 receptor, blocking virus cell entry, and neutralize all tested SARS-CoV-2 variants of concern. In a nonhuman primate model of SARS-CoV-2 infection, prophylactic AZD7442 administration prevented infection, whereas therapeutic administration accelerated virus clearance from lung. In an ongoing phase 1 study in healthy participants (NCT04507256), a 300 mg intramuscular injection of AZD7442 provided SARS-CoV-2 serum geometric mean neutralizing titers greater than 10-fold above those of convalescent serum for at least 3 months, which remained 3-fold above those of convalescent serum at 9 months post-AZD7442 administration. Approximately 1 to 2% of serum AZD7442 was detected in nasal mucosa, a site of SARS-CoV-2 infection. Extrapolation of the time course of serum AZD7442 concentration suggests AZD7442 may provide up to 12 months of protection and benefit individuals at high-risk of COVID-19.
. 2022 Jan 25;eabl8124.
doi: 10.1126/scitranslmed.abl8124. Online ahead of print.
The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in non-human primates and has an extended half-life in humans
Yueh-Ming Loo[SUP] 1 [/SUP], Patrick M McTamney[SUP] 1 [/SUP], Rosalinda H Arends[SUP] 2 [/SUP], Michael E Abram[SUP] 3 [/SUP], Anastasia A Aksyuk[SUP] 3 [/SUP], Seme Diallo[SUP] 1 [/SUP], Daniel J Flores[SUP] 1 [/SUP], Elizabeth J Kelly[SUP] 3 [/SUP], Kuishu Ren[SUP] 1 [/SUP], Richard Roque[SUP] 1 [/SUP], Kim Rosenthal[SUP] 1 [/SUP], Katie Streicher[SUP] 3 [/SUP], Kevin M Tuffy[SUP] 3 [/SUP], Nicholas J Bond[SUP] 4 [/SUP], Owen Cornwell[SUP] 4 [/SUP], Jerome Bouquet[SUP] 5 [/SUP], Lily I Cheng[SUP] 6 [/SUP], James Dunyak[SUP] 7 [/SUP], Yue Huang[SUP] 5 [/SUP], Anton I Rosenbaum[SUP] 5 [/SUP], Venkatesh Pilla Reddy[SUP] 8 [/SUP], Hanne Andersen[SUP] 9 [/SUP], Robert H Carnahan[SUP] 10 11 [/SUP], James E Crowe Jr[SUP] 10 11 12 [/SUP], Ana I Kuehne[SUP] 13 [/SUP], Andrew S Herbert[SUP] 13 [/SUP], John M Dye[SUP] 13 [/SUP], Helen Bright[SUP] 1 [/SUP], Nicole L Kallewaard[SUP] 1 [/SUP], Menelas N Pangalos[SUP] 14 [/SUP], Mark T Esser[SUP] 15 [/SUP]
Affiliations
- PMID: 35076282
- DOI: 10.1126/scitranslmed.abl8124
Abstract
Despite the success of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, there remains a need for more prevention and treatment options for individuals remaining at risk of coronavirus disease 2019 (COVID-19). Monoclonal antibodies (mAbs) against the viral spike protein have potential to both prevent and treat COVID-19, and reduce the risk of severe disease and death. Here, we describe AZD7442, a combination of two mAbs, AZD8895 (tixagevimab) and AZD1061 (cilgavimab), that simultaneously bind to distinct, nonoverlapping epitopes on the spike protein receptor binding domain to neutralize SARS-CoV-2. Initially isolated from individuals with prior SARS-CoV-2 infection, the two mAbs were designed to extend their half-lives and reduce effector functions. The AZD7442 mAbs individually prevent the spike protein from binding to angiotensin-converting enzyme 2 receptor, blocking virus cell entry, and neutralize all tested SARS-CoV-2 variants of concern. In a nonhuman primate model of SARS-CoV-2 infection, prophylactic AZD7442 administration prevented infection, whereas therapeutic administration accelerated virus clearance from lung. In an ongoing phase 1 study in healthy participants (NCT04507256), a 300 mg intramuscular injection of AZD7442 provided SARS-CoV-2 serum geometric mean neutralizing titers greater than 10-fold above those of convalescent serum for at least 3 months, which remained 3-fold above those of convalescent serum at 9 months post-AZD7442 administration. Approximately 1 to 2% of serum AZD7442 was detected in nasal mucosa, a site of SARS-CoV-2 infection. Extrapolation of the time course of serum AZD7442 concentration suggests AZD7442 may provide up to 12 months of protection and benefit individuals at high-risk of COVID-19.