Safety and immunogenicity of 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola vaccination in children and adolescents in Africa: A randomised, placebo-controlled, multicentre Phase II clinical trial

Abstract

Background Reoccurring Ebola outbreaks in West and Central Africa have led to serious illness and death in thousands of adults and children. The objective of this study was to assess safety, tolerability, and immunogenicity of the heterologous 2-dose Ad26.ZEBOV, MVA-BN-Filo vaccination regimen in adolescents and children in Africa. Methods and findings In this multicentre, randomised, observer-blind, placebo-controlled Phase II study, 131 adolescents (12 to 17 years old) and 132 children (4 to 11 years old) were enrolled from Eastern and Western Africa and randomised 5:1 to receive study vaccines or placebo. Vaccine groups received intramuscular injections of Ad26.ZEBOV (5 × 1010 viral particles) and MVA-BN-Filo (1 × 108 infectious units) 28 or 56 days apart; placebo recipients received saline. Primary outcomes were safety and tolerability. Solicited adverse events (AEs) were recorded until 7 days after each vaccination and serious AEs (SAEs) throughout the study. Secondary and exploratory outcomes were humoral immune responses (binding and neutralising Ebola virus [EBOV] glycoprotein [GP]-specific antibodies), up to 1 year after the first dose. Enrolment began on February 26, 2016, and the date of last participant last visit was November 28, 2018. Of the 263 participants enrolled, 217 (109 adolescents, 108 children) received the 2-dose regimen, and 43 (20 adolescents, 23 children) received 2 placebo doses. Median age was 14.0 (range 11 to 17) and 7.0 (range 4 to 11) years for adolescents and children, respectively. Fifty-four percent of the adolescents and 51% of the children were male. All participants were Africans, and, although there was a slight male preponderance overall, the groups were well balanced. No vaccine-related SAEs were reported; solicited AEs were mostly mild/moderate. Twenty-one days post-MVA-BN-Filo vaccination, binding antibody responses against EBOV GP were observed in 100% of vaccinees (106 adolescents, 104 children). Geometric mean concentrations tended to be higher after the 56-day interval (adolescents 13,532 ELISA units [EU]/mL, children 17,388 EU/mL) than the 28-day interval (adolescents 6,993 EU/mL, children 8,007 EU/mL). Humoral responses persisted at least up to Day 365. A limitation of the study is that the follow-up period was limited to 365 days for the majority of the participants, and so it was not possible to determine whether immune responses persisted beyond this time period. Additionally, formal statistical comparisons were not preplanned but were only performed post hoc. Conclusions The heterologous 2-dose vaccination was well tolerated in African adolescents and children with no vaccine-related SAEs. All vaccinees displayed anti-EBOV GP antibodies after the 2-dose regimen, with higher responses in the 56-day interval groups. The frequency of pyrexia after vaccine or placebo was higher in children than in adolescents. These data supported the prophylactic indication against EBOV disease in a paediatric population, as licenced in the EU. Trial registration ClinicalTrials.gov NCT02564523.

Non-human primate to human immunobridging demonstrates a protective effect of Ad26.ZEBOV, MVA-BN-Filo vaccine against Ebola

“…The primary immunobridging analysis was based on the pooled per-protocol immunogenicity (PPI) dataset of 764 healthy adults from five studies (EBL2001 [France, UK] 27 , 28 , EBL2002 [Burkina Faso, Côte d’Ivoire, Kenya, Uganda] 29 – 31 , EBL3001 [Sierra Leone] 32 – 34 , EBL3002 [USA] 35 , 36 , and EBL3003 [USA] 36 , 37 ). The baseline and demographic characteristics are summarized in Supplementary Table 1 in the Supplementary Appendix .…”

Developing capacity for implementation and evaluation of vaccine trials in Uganda: Perspective of the Makerere University Walter Reed Project

“…Staff actively contributed to the development of the National Guidelines for Research involving Humans as Research Participants, the Uganda National Health Laboratory Services policy and the national bio-safety and biosecurity guidelines and regulations. MUWRP has contributed to the body of scientific knowledge through presentations at national and international scientific meetings, with a total of six publications 26 , 28 , 30 , 31 , 34 , 35 with two as first author publications 26 , 28 generated from vaccine clinical trials. In addition, staff are members of key Ministry of Health technical working groups that develop guidelines for improved health care.…”

Marburg Virus Disease – A Mini-Review

“…For instance, testing in animal models has revealed the protective effect of a Vesicular stomatitis virus (VSV) (recombinant) based vaccine that expresses the glycoprotein (GP) of MARV (rVSVΔG-MARV-GP) (Marzi et al 2021). MVA-BN-Filo is another vaccine candidate that contains the antigens of both Ebola and Marburg virus, found to have a potential protective effect against both viruses (Anywaine et al 2022). Progress has been made in the development of vaccines based on recombinant glycoproteins of filoviruses viz., Ebola virus (EBOV) and Sudan virus (SUDV) along with MARV, for designing monovalent MARV vaccine, monovalent SUDV vaccine, and bivalent formulations.…”