The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in nonhuman primates and has an extended half-life in humans
Yueh-Ming Loo, Patrick M McTamney, Rosalinda H Arends, Michael E Abram, Anastasia A Aksyuk, Seme Diallo, Daniel J Flores, Elizabeth J Kelly, Kuishu Ren, Richard Roque, Kim Rosenthal, Katie Streicher, Kevin M Tuffy, Nicholas J Bond, Owen Cornwell, Jerome Bouquet, Lily I Cheng, James Dunyak, Yue Huang, Anton I Rosenbaum, Venkatesh Pilla Reddy, Hanne Andersen, Robert H Carnahan, James E Crowe Jr, Ana I Kuehne, Andrew S Herbert, John M Dye, Helen Bright, Nicole L Kallewaard, Menelas N Pangalos, Mark T Esser, Yueh-Ming Loo, Patrick M McTamney, Rosalinda H Arends, Michael E Abram, Anastasia A Aksyuk, Seme Diallo, Daniel J Flores, Elizabeth J Kelly, Kuishu Ren, Richard Roque, Kim Rosenthal, Katie Streicher, Kevin M Tuffy, Nicholas J Bond, Owen Cornwell, Jerome Bouquet, Lily I Cheng, James Dunyak, Yue Huang, Anton I Rosenbaum, Venkatesh Pilla Reddy, Hanne Andersen, Robert H Carnahan, James E Crowe Jr, Ana I Kuehne, Andrew S Herbert, John M Dye, Helen Bright, Nicole L Kallewaard, Menelas N Pangalos, Mark T Esser
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 the 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 threefold above those of convalescent serum at 9 months after AZD7442 administration. About 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.
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References
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Source: PubMed