Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials
Authors: Happe Myra , Hofstetter Amelia R. , Wang Jing , Yamshchikov Galina V. , Holman LaSonji A. , Novik Laura , Strom Larisa , Kiweewa Francis , Wakabi Salim , Millard Monica , Kelley Colleen F. , Kabbani Sarah , Edupuganti Srilatha , Beck Allison , Kaltovich Florence , Murray Tamar , Tsukerman Susanna , Carr Derick , Ashman Carl , Stanley Daphne A. , Ploquin Aurélie , Bailer Robert T. , Schwartz Richard , Cham Fatim , Tindikahwa Allan , Hu Zonghui , Gordon Ingelise J. , Rouphael Nadine , Houser Katherine V. , Coates Emily E. , Graham Barney S. , Koup Richard A. , Mascola John R. , Sullivan Nancy J. , Robb Merlin L. , Ake Julie A. , Lyke Kirsten E. , Mulligan Mark J. , Ledgerwood Julie E. , Kibuuka Hannah ,   the VRC 208 and RV 422 study team, Casazza Joseph P. , Chen Grace L. , Enama Mary E. , Gaudinski Martin R. , Hendel Cynthia Starr , Costner Pamela J. M. , Larkin Brenda , Mendoza Floreliz , Sanders Jamie , Whalen William R. , Zephir Kathryn L. , Straling Judith , DeCederfelt Hope , Conan-Cibotti Michelle , Stein Judy , Pittman Iris R. , Vasilenko Olga , DeZure Adam , Sitar Sandra , Dropulic Lesia K. , Plummer Sarah H. , Nguyen Thuy A. , Berkowitz Nina M. , Greenberg Nancy , Chrisley Lisa , Billington Melissa , Wang Xiaolin , Becker JoAnna , Campbell James D. , Chen Wilbur H. , Kwon Alyson , Dorsey Brenda , Courneya Jennifer , Komninou Panagiota , Lee Myounghee , Bower Mary , Bailey Charles A. , Nesheim Wendy , Girmay Tigisty , Xu Jianguo , Ogilvie Melinda , Sadowski Joann , Osinski Eileen , Lai Lilin , Grimes Vicki , Kamya Moses R. , Michael Nelson L. , Kajumba Francis , Ananworanich Jinantat , Mwesigwa Betty , Kimbugne Geofrey , Luzinda Kenneth , Nakabuye Immaculate , Mukyala Maureen G. , Kabahubya Mable , Nakibuuka Lydia , Matovu Robinah 
Published: March 2024

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.