Low-Dose Subcutaneous or Intravenous Monoclonal Antibody to Prevent Malaria
Richard L Wu, Azza H Idris, Nina M Berkowitz, Myra Happe, Martin R Gaudinski, Christian Buettner, Larisa Strom, Seemal F Awan, LaSonji A Holman, Floreliz Mendoza, Ingelise J Gordon, Zonghui Hu, Andrezza Campos Chagas, Lawrence T Wang, Lais Da Silva Pereira, Joseph R Francica, Neville K Kisalu, Barbara J Flynn, Wei Shi, Wing-Pui Kong, Sarah O'Connell, Sarah H Plummer, Allison Beck, Adrian McDermott, Sandeep R Narpala, Leonid Serebryannyy, Mike Castro, Rosa Silva, Marjaan Imam, Iris Pittman, Somia P Hickman, Andrew J McDougal, Ashly E Lukoskie, Jittawadee R Murphy, Jason G Gall, Kevin Carlton, Patricia Morgan, Ellie Seo, Judy A Stein, Sandra Vazquez, Shinyi Telscher, Edmund V Capparelli, Emily E Coates, John R Mascola, Julie E Ledgerwood, Lesia K Dropulic, Robert A Seder, VRC 614 Study Team, Joseph P Casazza, Alicia T Widge, Peter D Crompton, Douglas Rosing, Christopher L Case, Blake Warner, Olga Trofymenko, Abidemi Ola, Karen Parker, Priya Kamath, Laura Novik, Pamela Costner, Jamie Saunders, William Whalen, Xiaolin Wang, Jennifer Cunningham, Anita Arthur, Aba Eshun, Justine Jones, Jennifer Phipps, Preeti Apte, Renunda Hicks, LaShawn Requilman, Catina Evans, Pernell Williams, Jackie Stephens, Olga Vasilenko, Galina Yamshchikov, Stephanie Taylor, Charla Andrews, Mark O'Callahan, Thuy Nguyen, Hope Wilson, Kathy Zephir, Brenda Larkin, Ijeoma Ikpeama, Lorenzo Walker, Matthew Burrows, Leah Perazzo, Ying Jin-Clark, Ruth Woodward, John-Paul Todd, Liz Scheideman, Brandi France, Rajoshi Chaudhuri, Shireen Khayat, Rachel Prucnal, Jin Huang, Jane Rouse, Thomas Smith 3rd, Janel Holland-Linn, Nadia Amharref, Shamitha Shetty, Shing-Fen Kao, Elle Millender, Peifeng Chen, Robin Luedtke, Deonte Toliver, Flo Kaltovich, Manos Tzortzakakis, Daniel Gowetski, Yi-Hsin Fan, Prasanthi Bandi, Yoo-Jung Yang, Ivan Loukinov, Vibhuti Wadhwa, Kristin Leach, Krishna Gulla, Xin Wang, Farah Vejzagic, Vaidehi Bhagat, Erwin Rosales, Lana Hogan, Christine Anderson, Erin Reilly, Melissa Resto, Yile Li, Paula Lei, Migen Bimi, Lisa Kueltzo, Will Adams, Benjamin Clarkson, Richard L Wu, Azza H Idris, Nina M Berkowitz, Myra Happe, Martin R Gaudinski, Christian Buettner, Larisa Strom, Seemal F Awan, LaSonji A Holman, Floreliz Mendoza, Ingelise J Gordon, Zonghui Hu, Andrezza Campos Chagas, Lawrence T Wang, Lais Da Silva Pereira, Joseph R Francica, Neville K Kisalu, Barbara J Flynn, Wei Shi, Wing-Pui Kong, Sarah O'Connell, Sarah H Plummer, Allison Beck, Adrian McDermott, Sandeep R Narpala, Leonid Serebryannyy, Mike Castro, Rosa Silva, Marjaan Imam, Iris Pittman, Somia P Hickman, Andrew J McDougal, Ashly E Lukoskie, Jittawadee R Murphy, Jason G Gall, Kevin Carlton, Patricia Morgan, Ellie Seo, Judy A Stein, Sandra Vazquez, Shinyi Telscher, Edmund V Capparelli, Emily E Coates, John R Mascola, Julie E Ledgerwood, Lesia K Dropulic, Robert A Seder, VRC 614 Study Team, Joseph P Casazza, Alicia T Widge, Peter D Crompton, Douglas Rosing, Christopher L Case, Blake Warner, Olga Trofymenko, Abidemi Ola, Karen Parker, Priya Kamath, Laura Novik, Pamela Costner, Jamie Saunders, William Whalen, Xiaolin Wang, Jennifer Cunningham, Anita Arthur, Aba Eshun, Justine Jones, Jennifer Phipps, Preeti Apte, Renunda Hicks, LaShawn Requilman, Catina Evans, Pernell Williams, Jackie Stephens, Olga Vasilenko, Galina Yamshchikov, Stephanie Taylor, Charla Andrews, Mark O'Callahan, Thuy Nguyen, Hope Wilson, Kathy Zephir, Brenda Larkin, Ijeoma Ikpeama, Lorenzo Walker, Matthew Burrows, Leah Perazzo, Ying Jin-Clark, Ruth Woodward, John-Paul Todd, Liz Scheideman, Brandi France, Rajoshi Chaudhuri, Shireen Khayat, Rachel Prucnal, Jin Huang, Jane Rouse, Thomas Smith 3rd, Janel Holland-Linn, Nadia Amharref, Shamitha Shetty, Shing-Fen Kao, Elle Millender, Peifeng Chen, Robin Luedtke, Deonte Toliver, Flo Kaltovich, Manos Tzortzakakis, Daniel Gowetski, Yi-Hsin Fan, Prasanthi Bandi, Yoo-Jung Yang, Ivan Loukinov, Vibhuti Wadhwa, Kristin Leach, Krishna Gulla, Xin Wang, Farah Vejzagic, Vaidehi Bhagat, Erwin Rosales, Lana Hogan, Christine Anderson, Erin Reilly, Melissa Resto, Yile Li, Paula Lei, Migen Bimi, Lisa Kueltzo, Will Adams, Benjamin Clarkson
Abstract
Background: New approaches for the prevention and elimination of malaria, a leading cause of illness and death among infants and young children globally, are needed.
Methods: We conducted a phase 1 clinical trial to assess the safety and pharmacokinetics of L9LS, a next-generation antimalarial monoclonal antibody, and its protective efficacy against controlled human malaria infection in healthy adults who had never had malaria or received a vaccine for malaria. The participants received L9LS either intravenously or subcutaneously at a dose of 1 mg, 5 mg, or 20 mg per kilogram of body weight. Within 2 to 6 weeks after the administration of L9LS, both the participants who received L9LS and the control participants underwent controlled human malaria infection in which they were exposed to mosquitoes carrying Plasmodium falciparum (3D7 strain).
Results: No safety concerns were identified. L9LS had an estimated half-life of 56 days, and it had dose linearity, with the highest mean (±SD) maximum serum concentration (Cmax) of 914.2±146.5 μg per milliliter observed in participants who had received 20 mg per kilogram intravenously and the lowest mean Cmax of 41.5±4.7 μg per milliliter observed in those who had received 1 mg per kilogram intravenously; the mean Cmax was 164.8±31.1 in the participants who had received 5 mg per kilogram intravenously and 68.9±22.3 in those who had received 5 mg per kilogram subcutaneously. A total of 17 L9LS recipients and 6 control participants underwent controlled human malaria infection. Of the 17 participants who received a single dose of L9LS, 15 (88%) were protected after controlled human malaria infection. Parasitemia did not develop in any of the participants who received 5 or 20 mg per kilogram of intravenous L9LS. Parasitemia developed in 1 of 5 participants who received 1 mg per kilogram intravenously, 1 of 5 participants who received 5 mg per kilogram subcutaneously, and all 6 control participants through 21 days after the controlled human malaria infection. Protection conferred by L9LS was seen at serum concentrations as low as 9.2 μg per milliliter.
Conclusions: In this small trial, L9LS administered intravenously or subcutaneously protected recipients against malaria after controlled infection, without evident safety concerns. (Funded by the National Institute of Allergy and Infectious Diseases; VRC 614 ClinicalTrials.gov number, NCT05019729.).
Copyright © 2022 Massachusetts Medical Society.
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Source: PubMed