Safety and Immunogenicity of an Accelerated Ebola Vaccination Schedule in People with and without Human Immunodeficiency Virus: A Randomized Clinical Trial

Julie A Ake; Kristopher Paolino; Jack N Hutter; Susan Biggs Cicatelli; Leigh Anne Eller; Michael A Eller; Margaret C Costanzo; Dominic Paquin-Proulx; Merlin L Robb; Chi L Tran; Lalaine Anova; Linda L Jagodzinski; Lucy A Ward; Nicole Kilgore; Janice Rusnak; Callie Bounds; Christopher S Badorrek; Jay W Hooper; Steven A Kwilas; Ine Ilsbroux; Dickson Nkafu Anumendem; Auguste Gaddah; Georgi Shukarev; Viki Bockstal; Kerstin Luhn; Macaya Douoguih; Cynthia Robinson

doi:10.3390/vaccines12050497

Safety and Immunogenicity of an Accelerated Ebola Vaccination Schedule in People with and without Human Immunodeficiency Virus: A Randomized Clinical Trial

Vaccines (Basel). 2024 May 4;12(5):497. doi: 10.3390/vaccines12050497.

Authors

Julie A Ake¹, Kristopher Paolino², Jack N Hutter², Susan Biggs Cicatelli³, Leigh Anne Eller^{1

4}, Michael A Eller^{1

4}, Margaret C Costanzo^{1

4}, Dominic Paquin-Proulx^{1

4}, Merlin L Robb^{1

4}, Chi L Tran^{1

4}, Lalaine Anova^{1

4}, Linda L Jagodzinski⁵, Lucy A Ward⁶, Nicole Kilgore⁶, Janice Rusnak⁶, Callie Bounds⁶, Christopher S Badorrek⁶, Jay W Hooper⁷, Steven A Kwilas⁷, Ine Ilsbroux⁸, Dickson Nkafu Anumendem⁸, Auguste Gaddah⁸, Georgi Shukarev⁹, Viki Bockstal⁹, Kerstin Luhn⁹, Macaya Douoguih⁹, Cynthia Robinson⁹

Affiliations

¹ U.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
² Clinical Trials Center, Center for Enabling Capabilities, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
³ ICON Government and Public Health Solutions, Silver Spring, MD 20901, USA.
⁴ Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD 20817, USA.
⁵ Diagnostics and Countermeasures Branch, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
⁶ Joint Project Manager for Chemical, Biological, Radiological, and Nuclear Medical, U.S. Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense, Fort Detrick, MD 21702, USA.
⁷ Virology Division, U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, MD 21702, USA.
⁸ Janssen Research & Development, 2340 Beerse, Belgium.
⁹ Janssen Vaccines & Prevention B.V., 2333 Leiden, The Netherlands.

Abstract

The safety and immunogenicity of the two-dose Ebola vaccine regimen MVA-BN-Filo, Ad26.ZEBOV, 14 days apart, was evaluated in people without HIV (PWOH) and living with HIV (PLWH). In this observer-blind, placebo-controlled, phase 2 trial, healthy adults were randomized (4:1) to receive MVA-BN-Filo (dose 1) and Ad26.ZEBOV (dose 2), or two doses of saline/placebo, administered intramuscularly 14 days apart. The primary endpoints were safety (adverse events (AEs)) and immunogenicity (Ebola virus (EBOV) glycoprotein-specific binding antibody responses). Among 75 participants (n = 50 PWOH; n = 25 PLWH), 37% were female, the mean age was 44 years, and 56% were Black/African American. AEs were generally mild/moderate, with no vaccine-related serious AEs. At 21 days post-dose 2, EBOV glycoprotein-specific binding antibody responder rates were 100% among PWOH and 95% among PLWH; geometric mean antibody concentrations were 6286 EU/mL (n = 36) and 2005 EU/mL (n = 19), respectively. A total of 45 neutralizing and other functional antibody responses were frequently observed. Ebola-specific CD4+ and CD8+ T-cell responses were polyfunctional and durable to at least 12 months post-dose 2. The regimen was well tolerated and generated robust, durable immune responses in PWOH and PLWH. Findings support continued evaluation of accelerated vaccine schedules for rapid deployment in populations at immediate risk. Trial registration: NCT02598388 (submitted 14 November 2015).

Keywords: Ebola virus; immunogenicity; vaccine safety.

Associated data

ClinicalTrials.gov/NCT02598388

Grants and funding

This work was supported by Janssen Pharmaceuticals, who participated in the design and conduct of the study, safety monitoring, data analysis and interpretation, preparation, review, and approval of the manuscript, and the decision to submit the manuscript for publication. This study was also funded by JPM-CBRN Medical, who participated in the design of the study, safety monitoring, data analysis and interpretation, and review and approval of the manuscript. This work was supported by Janssen Vaccines & Prevention B.V.; the U.S. Department of Defense’s Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND); and the Joint Project Manager for Chemical, Biological, Radiological and Nuclear Medical (JPM-CBRN Medical), with support from a contract between Janssen Vaccines & Prevention B.V. and the Henry M. Jackson Foundation for the Advancement of Military Medicine (W81XWH-16-0086) and a cooperative agreement (W81XWH-11-2-0174) between the Henry M. Jackson Foundation for the Advancement of Military Medicine and the U.S. Department of Defense. The U.S. Army Medical Research Acquisition Activity is the awarding and administering acquisition office for the cooperative agreement. Funding for medical writing and editorial assistance was provided by Janssen Vaccines & Prevention B.V.