Preclinical development of a replication-competent vesicular stomatitis virus-based Lassa virus vaccine candidate advanced into human clinical trialsResearch in context
Summary: Background: Lassa fever (LF) is a zoonotic haemorrhagic disease caused by Lassa virus (LASV), which is endemic in West African countries. The multimammate rat is the main animal reservoir and its geographic range is expected to expand due to influences like climate change and land usage, a...
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Elsevier
2025-04-01
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| author | Christopher L. Cooper Gavin Morrow Maoli Yuan Thomas S. Postler Maxwell L. Neal Robert W. Cross Courtney Woolsey Krystle N. Agans Viktoriya Borisevich Ryan P. McNamara Caroline Atyeo Vicky Roy Daritza Germosen Fuxiang Hou Shui L. Li Lucia Reiserova Yesle Choi Aaron Wilson Denise Wagner Olivia Wallace-Selman Alexei Carpov Fuqiang Geng Deborah J. Frederick Joanne DeStefano Anne M. Ercolini Adrian S. Enriquez Kathryn M. Hastie Suzane Ramos da Silva Eddy Sayeed John W. Coleman Andrew Kilianski Galit Alter Erica Ollmann Saphire John D. Aitchison Thomas W. Geisbert Swati B. Gupta Mark B. Feinberg Christopher L. Parks |
| author_facet | Christopher L. Cooper Gavin Morrow Maoli Yuan Thomas S. Postler Maxwell L. Neal Robert W. Cross Courtney Woolsey Krystle N. Agans Viktoriya Borisevich Ryan P. McNamara Caroline Atyeo Vicky Roy Daritza Germosen Fuxiang Hou Shui L. Li Lucia Reiserova Yesle Choi Aaron Wilson Denise Wagner Olivia Wallace-Selman Alexei Carpov Fuqiang Geng Deborah J. Frederick Joanne DeStefano Anne M. Ercolini Adrian S. Enriquez Kathryn M. Hastie Suzane Ramos da Silva Eddy Sayeed John W. Coleman Andrew Kilianski Galit Alter Erica Ollmann Saphire John D. Aitchison Thomas W. Geisbert Swati B. Gupta Mark B. Feinberg Christopher L. Parks |
| author_sort | Christopher L. Cooper |
| collection | DOAJ |
| description | Summary: Background: Lassa fever (LF) is a zoonotic haemorrhagic disease caused by Lassa virus (LASV), which is endemic in West African countries. The multimammate rat is the main animal reservoir and its geographic range is expected to expand due to influences like climate change and land usage, and this will place larger parts of Africa at risk. We conducted preclinical development on a promising experimental vaccine that allowed its advancement into human trials. Methods: The LF vaccine is based on a vesicular stomatitis virus (VSV) vector in which the VSV glycoprotein (G) was replaced with the LASV glycoprotein complex (GPC). Earlier studies showed that this vaccine (VSVΔG-LASV-GPC) was efficacious in macaques, thus we regenerated VSVΔG-LASV-GPC using laboratory and documentation practices required to support vaccine manufacturing and human trials. The efficacy of the clinical vaccine candidate was assessed in cynomolgus macaques and more extensive immunologic analysis was performed than previously to investigate immune responses associated with protection. Findings: A single VSVΔG-LASV-GPC vaccination elicited innate, humoural and cellular immune responses, prevented development of substantial LASV viraemia, and protected animals from disease. Vaccinated macaques developed polyfunctional antibodies and serum was shown to neutralize virus expressing GPCs representative of geographically diverse LASV lineages. Interpretation: The VSVΔG-LASV-GPC clinical candidate elicited immunity that protected 10 of 10 vaccinated macaques from disease supporting its use in a clinical development program, which recently progressed to phase 2 clinical trials. Moreover, immunologic analysis showed that virus-neutralizing serum antibodies likely played a role in preventing LASV disease in vaccinated macaques. Funding: This work was supported by the Coalition for Epidemic Preparedness Innovations (CEPI), The National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH), The Bill and Melinda Gates Global Vaccine Accelerator Program, the Burroughs Wellcome Fund, and financial gifts and support by Nancy Zimmerman, Mark and Lisa Schwartz, and Terry and Susan Ragon. |
| format | Article |
| id | doaj-art-7972db8f70844e2eabc1d7446247d4f4 |
| institution | OA Journals |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj-art-7972db8f70844e2eabc1d7446247d4f42025-08-20T02:10:20ZengElsevierEBioMedicine2352-39642025-04-0111410564710.1016/j.ebiom.2025.105647Preclinical development of a replication-competent vesicular stomatitis virus-based Lassa virus vaccine candidate advanced into human clinical trialsResearch in contextChristopher L. Cooper0Gavin Morrow1Maoli Yuan2Thomas S. Postler3Maxwell L. Neal4Robert W. Cross5Courtney Woolsey6Krystle N. Agans7Viktoriya Borisevich8Ryan P. McNamara9Caroline Atyeo10Vicky Roy11Daritza Germosen12Fuxiang Hou13Shui L. Li14Lucia Reiserova15Yesle Choi16Aaron Wilson17Denise Wagner18Olivia Wallace-Selman19Alexei Carpov20Fuqiang Geng21Deborah J. Frederick22Joanne DeStefano23Anne M. Ercolini24Adrian S. Enriquez25Kathryn M. Hastie26Suzane Ramos da Silva27Eddy Sayeed28John W. Coleman29Andrew Kilianski30Galit Alter31Erica Ollmann Saphire32John D. Aitchison33Thomas W. Geisbert34Swati B. Gupta35Mark B. Feinberg36Christopher L. Parks37IAVI, Vaccine Design and Development Laboratory, Jersey City, NJ 07302, USAIAVI, Vaccine Design and Development Laboratory, Jersey City, NJ 07302, USAIAVI, Vaccine Design and Development Laboratory, Jersey City, NJ 07302, USAIAVI, Vaccine Design and Development Laboratory, Jersey City, NJ 07302, USACenter for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USAGalveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USAGalveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USAGalveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USAGalveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USARagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Cambridge, MA 02139, USARagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Cambridge, MA 02139, USARagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Cambridge, MA 02139, USARagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Cambridge, MA 02139, USAIAVI, Vaccine Design and Development Laboratory, Jersey City, NJ 07302, USAIAVI, Vaccine Design and Development Laboratory, Jersey City, NJ 07302, USAIAVI, Vaccine Design and Development Laboratory, Jersey City, NJ 07302, USAIAVI, Vaccine Design and Development Laboratory, Jersey City, NJ 07302, USAIAVI, Vaccine Design and Development Laboratory, Jersey City, NJ 07302, USAIAVI, Vaccine Design and Development Laboratory, Jersey City, NJ 07302, USAIAVI, Vaccine Design and Development Laboratory, Jersey City, NJ 07302, USAIAVI, Vaccine Design and Development Laboratory, Jersey City, NJ 07302, USAIAVI, Vaccine Design and Development Laboratory, Jersey City, NJ 07302, USAIAVI, Vaccine Design and Development Laboratory, Jersey City, NJ 07302, USAIAVI, Vaccine Design and Development Laboratory, Jersey City, NJ 07302, USAIAVI, Vaccine Design and Development Laboratory, Jersey City, NJ 07302, USACenter for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA 92037, USAIAVI, Vaccine Design and Development Laboratory, Jersey City, NJ 07302, USAIAVI, New York, NY 10004, USAIAVI, Vaccine Design and Development Laboratory, Jersey City, NJ 07302, USAIAVI, New York, NY 10004, USARagon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard, Cambridge, MA 02139, USACenter for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA 92037, USACenter for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA; Departments of Pediatrics and Biochemistry, University of Washington, Seattle, WA 98109, USAGalveston National Laboratory, University of Texas Medical Branch, Galveston, TX 77555, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USAIAVI, New York, NY 10004, USAIAVI, New York, NY 10004, USAIAVI, Vaccine Design and Development Laboratory, Jersey City, NJ 07302, USA; Corresponding author.Summary: Background: Lassa fever (LF) is a zoonotic haemorrhagic disease caused by Lassa virus (LASV), which is endemic in West African countries. The multimammate rat is the main animal reservoir and its geographic range is expected to expand due to influences like climate change and land usage, and this will place larger parts of Africa at risk. We conducted preclinical development on a promising experimental vaccine that allowed its advancement into human trials. Methods: The LF vaccine is based on a vesicular stomatitis virus (VSV) vector in which the VSV glycoprotein (G) was replaced with the LASV glycoprotein complex (GPC). Earlier studies showed that this vaccine (VSVΔG-LASV-GPC) was efficacious in macaques, thus we regenerated VSVΔG-LASV-GPC using laboratory and documentation practices required to support vaccine manufacturing and human trials. The efficacy of the clinical vaccine candidate was assessed in cynomolgus macaques and more extensive immunologic analysis was performed than previously to investigate immune responses associated with protection. Findings: A single VSVΔG-LASV-GPC vaccination elicited innate, humoural and cellular immune responses, prevented development of substantial LASV viraemia, and protected animals from disease. Vaccinated macaques developed polyfunctional antibodies and serum was shown to neutralize virus expressing GPCs representative of geographically diverse LASV lineages. Interpretation: The VSVΔG-LASV-GPC clinical candidate elicited immunity that protected 10 of 10 vaccinated macaques from disease supporting its use in a clinical development program, which recently progressed to phase 2 clinical trials. Moreover, immunologic analysis showed that virus-neutralizing serum antibodies likely played a role in preventing LASV disease in vaccinated macaques. Funding: This work was supported by the Coalition for Epidemic Preparedness Innovations (CEPI), The National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH), The Bill and Melinda Gates Global Vaccine Accelerator Program, the Burroughs Wellcome Fund, and financial gifts and support by Nancy Zimmerman, Mark and Lisa Schwartz, and Terry and Susan Ragon.http://www.sciencedirect.com/science/article/pii/S235239642500091XLassa virusVesicular stomatitis virus vectorClinical vaccine candidateNeutralizing antibodies |
| spellingShingle | Christopher L. Cooper Gavin Morrow Maoli Yuan Thomas S. Postler Maxwell L. Neal Robert W. Cross Courtney Woolsey Krystle N. Agans Viktoriya Borisevich Ryan P. McNamara Caroline Atyeo Vicky Roy Daritza Germosen Fuxiang Hou Shui L. Li Lucia Reiserova Yesle Choi Aaron Wilson Denise Wagner Olivia Wallace-Selman Alexei Carpov Fuqiang Geng Deborah J. Frederick Joanne DeStefano Anne M. Ercolini Adrian S. Enriquez Kathryn M. Hastie Suzane Ramos da Silva Eddy Sayeed John W. Coleman Andrew Kilianski Galit Alter Erica Ollmann Saphire John D. Aitchison Thomas W. Geisbert Swati B. Gupta Mark B. Feinberg Christopher L. Parks Preclinical development of a replication-competent vesicular stomatitis virus-based Lassa virus vaccine candidate advanced into human clinical trialsResearch in context EBioMedicine Lassa virus Vesicular stomatitis virus vector Clinical vaccine candidate Neutralizing antibodies |
| title | Preclinical development of a replication-competent vesicular stomatitis virus-based Lassa virus vaccine candidate advanced into human clinical trialsResearch in context |
| title_full | Preclinical development of a replication-competent vesicular stomatitis virus-based Lassa virus vaccine candidate advanced into human clinical trialsResearch in context |
| title_fullStr | Preclinical development of a replication-competent vesicular stomatitis virus-based Lassa virus vaccine candidate advanced into human clinical trialsResearch in context |
| title_full_unstemmed | Preclinical development of a replication-competent vesicular stomatitis virus-based Lassa virus vaccine candidate advanced into human clinical trialsResearch in context |
| title_short | Preclinical development of a replication-competent vesicular stomatitis virus-based Lassa virus vaccine candidate advanced into human clinical trialsResearch in context |
| title_sort | preclinical development of a replication competent vesicular stomatitis virus based lassa virus vaccine candidate advanced into human clinical trialsresearch in context |
| topic | Lassa virus Vesicular stomatitis virus vector Clinical vaccine candidate Neutralizing antibodies |
| url | http://www.sciencedirect.com/science/article/pii/S235239642500091X |
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