Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials
Abstract Ebola virus disease (EVD) is a filoviral infection caused by virus species of the Ebolavirus genus including Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV). We investigated the safety and immunogenicity of a heterologous prime-boost regimen involving a chimpanzee adenovirus 3 vectored...
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Nature Portfolio
2024-03-01
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| Online Access: | https://doi.org/10.1038/s41541-024-00833-z |
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| author | Myra Happe Amelia R. Hofstetter Jing Wang Galina V. Yamshchikov LaSonji A. Holman Laura Novik Larisa Strom Francis Kiweewa Salim Wakabi Monica Millard Colleen F. Kelley Sarah Kabbani Srilatha Edupuganti Allison Beck Florence Kaltovich Tamar Murray Susanna Tsukerman Derick Carr Carl Ashman Daphne A. Stanley Aurélie Ploquin Robert T. Bailer Richard Schwartz Fatim Cham Allan Tindikahwa Zonghui Hu Ingelise J. Gordon Nadine Rouphael Katherine V. Houser Emily E. Coates Barney S. Graham Richard A. Koup John R. Mascola Nancy J. Sullivan Merlin L. Robb Julie A. Ake Kirsten E. Lyke Mark J. Mulligan Julie E. Ledgerwood Hannah Kibuuka the VRC 208 and RV 422 study team |
| author_facet | Myra Happe Amelia R. Hofstetter Jing Wang Galina V. Yamshchikov LaSonji A. Holman Laura Novik Larisa Strom Francis Kiweewa Salim Wakabi Monica Millard Colleen F. Kelley Sarah Kabbani Srilatha Edupuganti Allison Beck Florence Kaltovich Tamar Murray Susanna Tsukerman Derick Carr Carl Ashman Daphne A. Stanley Aurélie Ploquin Robert T. Bailer Richard Schwartz Fatim Cham Allan Tindikahwa Zonghui Hu Ingelise J. Gordon Nadine Rouphael Katherine V. Houser Emily E. Coates Barney S. Graham Richard A. Koup John R. Mascola Nancy J. Sullivan Merlin L. Robb Julie A. Ake Kirsten E. Lyke Mark J. Mulligan Julie E. Ledgerwood Hannah Kibuuka the VRC 208 and RV 422 study team |
| author_sort | Myra Happe |
| collection | DOAJ |
| description | Abstract Ebola virus disease (EVD) is a filoviral infection caused by virus species of the Ebolavirus genus including Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV). We investigated the safety and immunogenicity of a heterologous prime-boost regimen involving a chimpanzee adenovirus 3 vectored Ebola vaccine [either monovalent (cAd3-EBOZ) or bivalent (cAd3-EBO)] prime followed by a recombinant modified vaccinia virus Ankara EBOV vaccine (MVA-EbolaZ) boost in two phase 1/1b randomized open-label clinical trials in healthy adults in the United States (US) and Uganda (UG). Trial US (NCT02408913) enrolled 140 participants, including 26 EVD vaccine-naïve and 114 cAd3-Ebola-experienced participants (April-November 2015). Trial UG (NCT02354404) enrolled 90 participants, including 60 EVD vaccine-naïve and 30 DNA Ebola vaccine-experienced participants (February-April 2015). All tested vaccines and regimens were safe and well tolerated with no serious adverse events reported related to study products. Solicited local and systemic reactogenicity was mostly mild to moderate in severity. The heterologous prime-boost regimen was immunogenic, including induction of durable antibody responses which peaked as early as two weeks and persisted up to one year after each vaccination. Different prime-boost intervals impacted the magnitude of humoral and cellular immune responses. The results from these studies demonstrate promising implications for use of these vaccines in both prophylactic and outbreak settings. |
| format | Article |
| id | doaj-art-a738fdd17f884be498b68c55cc2e29cd |
| institution | Kabale University |
| issn | 2059-0105 |
| language | English |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
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| series | npj Vaccines |
| spelling | doaj-art-a738fdd17f884be498b68c55cc2e29cd2025-02-02T12:07:32ZengNature Portfolionpj Vaccines2059-01052024-03-019111110.1038/s41541-024-00833-zHeterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trialsMyra Happe0Amelia R. Hofstetter1Jing Wang2Galina V. Yamshchikov3LaSonji A. Holman4Laura Novik5Larisa Strom6Francis Kiweewa7Salim Wakabi8Monica Millard9Colleen F. Kelley10Sarah Kabbani11Srilatha Edupuganti12Allison Beck13Florence Kaltovich14Tamar Murray15Susanna Tsukerman16Derick Carr17Carl Ashman18Daphne A. Stanley19Aurélie Ploquin20Robert T. Bailer21Richard Schwartz22Fatim Cham23Allan Tindikahwa24Zonghui Hu25Ingelise J. Gordon26Nadine Rouphael27Katherine V. Houser28Emily E. Coates29Barney S. Graham30Richard A. Koup31John R. Mascola32Nancy J. Sullivan33Merlin L. Robb34Julie A. Ake35Kirsten E. Lyke36Mark J. Mulligan37Julie E. Ledgerwood38Hannah Kibuuka39the VRC 208 and RV 422 study teamVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthClinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer ResearchVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthMakerere University-Walter Reed ProjectMakerere University-Walter Reed ProjectWalter Reed Army Institute of ResearchDepartment of Medicine, Division of Infectious Diseases, The Hope Clinic of the Emory Vaccine Center, Emory UniversityDepartment of Medicine, Division of Infectious Diseases, The Hope Clinic of the Emory Vaccine Center, Emory UniversityDepartment of Medicine, Division of Infectious Diseases, The Hope Clinic of the Emory Vaccine Center, Emory UniversityDepartment of Medicine, Division of Infectious Diseases, The Hope Clinic of the Emory Vaccine Center, Emory UniversityVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthMakerere University-Walter Reed ProjectMakerere University-Walter Reed ProjectBiostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthDepartment of Medicine, Division of Infectious Diseases, The Hope Clinic of the Emory Vaccine Center, Emory UniversityVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthWalter Reed Army Institute of ResearchWalter Reed Army Institute of ResearchUniversity of Maryland School of Medicine, Center for Vaccine Development and Global HealthDepartment of Medicine, Division of Infectious Diseases, The Hope Clinic of the Emory Vaccine Center, Emory UniversityVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthMakerere University-Walter Reed ProjectAbstract Ebola virus disease (EVD) is a filoviral infection caused by virus species of the Ebolavirus genus including Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV). We investigated the safety and immunogenicity of a heterologous prime-boost regimen involving a chimpanzee adenovirus 3 vectored Ebola vaccine [either monovalent (cAd3-EBOZ) or bivalent (cAd3-EBO)] prime followed by a recombinant modified vaccinia virus Ankara EBOV vaccine (MVA-EbolaZ) boost in two phase 1/1b randomized open-label clinical trials in healthy adults in the United States (US) and Uganda (UG). Trial US (NCT02408913) enrolled 140 participants, including 26 EVD vaccine-naïve and 114 cAd3-Ebola-experienced participants (April-November 2015). Trial UG (NCT02354404) enrolled 90 participants, including 60 EVD vaccine-naïve and 30 DNA Ebola vaccine-experienced participants (February-April 2015). All tested vaccines and regimens were safe and well tolerated with no serious adverse events reported related to study products. Solicited local and systemic reactogenicity was mostly mild to moderate in severity. The heterologous prime-boost regimen was immunogenic, including induction of durable antibody responses which peaked as early as two weeks and persisted up to one year after each vaccination. Different prime-boost intervals impacted the magnitude of humoral and cellular immune responses. The results from these studies demonstrate promising implications for use of these vaccines in both prophylactic and outbreak settings.https://doi.org/10.1038/s41541-024-00833-z |
| spellingShingle | Myra Happe Amelia R. Hofstetter Jing Wang Galina V. Yamshchikov LaSonji A. Holman Laura Novik Larisa Strom Francis Kiweewa Salim Wakabi Monica Millard Colleen F. Kelley Sarah Kabbani Srilatha Edupuganti Allison Beck Florence Kaltovich Tamar Murray Susanna Tsukerman Derick Carr Carl Ashman Daphne A. Stanley Aurélie Ploquin Robert T. Bailer Richard Schwartz Fatim Cham Allan Tindikahwa Zonghui Hu Ingelise J. Gordon Nadine Rouphael Katherine V. Houser Emily E. Coates Barney S. Graham Richard A. Koup John R. Mascola Nancy J. Sullivan Merlin L. Robb Julie A. Ake Kirsten E. Lyke Mark J. Mulligan Julie E. Ledgerwood Hannah Kibuuka the VRC 208 and RV 422 study team Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials npj Vaccines |
| title | Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials |
| title_full | Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials |
| title_fullStr | Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials |
| title_full_unstemmed | Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials |
| title_short | Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials |
| title_sort | heterologous cad3 ebola and mva ebolaz vaccines are safe and immunogenic in us and uganda phase 1 1b trials |
| url | https://doi.org/10.1038/s41541-024-00833-z |
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