GSK3390107 / GSK - LARVOL DELTA

Immunogenicity and safety of Ebola vaccines in children: a systematic review and meta-analysis. (PubMed, Int J Infect Dis) - "Ebola vaccines are safe and immunogenic in children. Findings support including children in vaccination campaigns, tailoring protocols to vaccine profiles and outbreak contexts."

Journal • Retrospective data • Ebola Virus Disease • Hematological Disorders • Infectious Disease • Pediatrics

Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials. (PubMed, NPJ Vaccines) - P1, P1b | "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)...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."

Journal • P1 data • Ebola Virus Disease • Infectious Disease

Partnership for Research on Ebola Vaccines in Liberia (PREVAIL) (clinicaltrials.gov) - P2; N=1500; Completed; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Active, not recruiting ➔ Completed

Trial completion • Infectious Disease

"ChAd3-EBO-Z ( Adenovirus vector. )" (@MarkPlackett1)

Designs and Characterization of Subunit Ebola GP Vaccine Candidates: Implications for Immunogenicity. (PubMed, Front Immunol) - "Interestingly, the trimeric GPs, a native-like GP complex, showed stronger affinity for antibodies raised by natural infection in EBOV disease survivors rather than for antibodies raised in volunteers that received the ChAd3-EBOZ vaccine. These results support our hypothesis that neutralizing antibodies are preferentially induced when using a native-like conformation of the GP antigen. The soluble trimeric recombinant GP proteins we developed represent a novel and promising strategy to develop prophylactic vaccines against EBOV and other filoviruses."

Journal • Infectious Disease

Safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in adults in Africa: a randomised, observer-blind, placebo-controlled, phase 2 trial. (PubMed, Lancet Infect Dis) - P2 | "ChAd3-EBO-Z was immunogenic and well tolerated in adults. Our findings provide a strong basis for future development steps, which should concentrate on multivalent approaches (including Sudan and Marburg strains). Additionally, prime-boost approaches should be a focus with a ChAd3-based vaccine for priming and boosted by a modified vaccinia Ankara-based vaccine."

Clinical • Journal • P2 data • Hematological Disorders • Infectious Disease • Pain • Thrombocytopenia

Safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in children in Africa: a randomised, observer-blind, placebo-controlled, phase 2 trial. (PubMed, Lancet Infect Dis) - P2 | "ChAd3-EBO-Z was immunogenic and well tolerated in children aged 1-17 years. This study provides the first ChAd3-EBO-Z data in a paediatric population. Further development should focus on multivalent approaches including Sudan and Marburg strains, and heterologous prime-boost strategies, for instance using modified vaccinia Ankara-based vaccine to boost the immune response."

Clinical • Journal • P2 data • Hematological Disorders • Infectious Disease • Pain • Pediatrics • Tetanus • Thrombocytopenia

Reduced Ebola vaccine responses in CMV+ young adults is associated with expansion of CD57+KLRG1+ T cells. (PubMed, J Exp Med) - "In this study, healthy UK and Senegalese adults aged 18-50 yr (average, 29 yr) were vaccinated with the Ebola vaccine candidate chimpanzee adenovirus type 3-vectored Ebola Zaire vaccine (ChAd3-EBO-Z) and boosted with modified vaccinia Ankara Ebola Zaire-vectored (MVA-EBO-Z) vaccine...Ebola-specific T cell responses induced by vaccination also contained significantly increased frequencies of terminally differentiated CD57+KLRG1+ cells in CMV seropositive (CMV+) individuals. This study suggests that CMV can also affect vaccine responses in younger adults and may have a particularly marked impact in many developing countries where CMV seroprevalence is almost universal."

Clinical • Journal • Cytomegalovirus Infection • CD57

A Trial to Evaluate the Safety and Systems Biology Response of Ebolavirus Zaire Vaccine (ChAd3-EBO-Z) (clinicaltrials.gov) - P1; N=60; Recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Not yet recruiting ➔ Recruiting

Enrollment open • Biosimilar

A Study to Evaluate the Safety and Immunogenicity of a Candidate Ebola Vaccine in Children (clinicaltrials.gov) - P2; N=600; Active, not recruiting; Sponsor: GlaxoSmithKline; Recruiting ➔ Active, not recruiting

Enrollment closed • Biosimilar • Immunology

Partnership for Research on Ebola Vaccines in Liberia (PREVAIL) (clinicaltrials.gov) - P2; N=1500; Active, not recruiting; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Trial primary completion date: Jun 2015 ➔ Jun 2016

Trial primary completion date • Biosimilar

A Phase I Study to Assess Ebola Vaccines cAd3-EBO Z and MVA-EBO Z (clinicaltrials.gov) - P1; N=38; Active, not recruiting; Sponsor: University of Oxford; Trial primary completion date: Dec 2015 ➔ Jun 2016

Trial primary completion date • Biosimilar • Immunology

A Trial to Evaluate the Safety and Systems Biology Response of Ebolavirus Zaire Vaccine (ChAd3-EBO-Z) (clinicaltrials.gov) - P1; N=61; Completed; Sponsor: National Institute of Allergy and Infectious Diseases (NIAID); Recruiting ➔ Completed; Trial completion date: Aug 2020 ➔ Jan 2020

Trial completion • Trial completion date

Nonclinical safety assessment of repeated administration and biodistribution of ChAd3-EBO-Z Ebola candidate vaccine. (PubMed, J Appl Toxicol) - "As expected, microscopic observations 3 days after the second injection were related to the elicited inflammatory reaction, and these inflammatory responses had almost completely disappeared 29 days after the second immunization. In conclusion, the vaccine was locally and systemically well-tolerated and the viral vector was partially or totally cleared from the organs where it disseminated, supporting the clinical development of the vaccine."

Clinical • Journal • CRP

Safety and immunogenicity of a heterologous prime-boost Ebola virus vaccine regimen - ChAd3-EBO-Z followed by MVA-EBO-Z in healthy adults in the UK and Senegal. (PubMed, J Infect Dis) - P1; "We undertook 2 phase 1 studies assessing safety and immunogenicity of the viral vector modified vaccinia Ankara virus vectored Ebola Zaire vaccine (MVA-EBO-Z), manufactured rapidly on a new duck cell line either alone or in a heterologous prime-boost regimen with recombinant chimpanzee adenovirus type 3 vectored Ebola Zaire vaccine (ChAd3-EBO-Z) followed by MVA-EBO-Z...MVA biomanufactured on an immortalised duck cell line shows potential for very large-scale manufacturing with lower cost of goods. This first trial of MVA-EBO-Z in humans encourages further testing in Phase II studies with the one week prime-boost interval regimen appearing particularly suitable for outbreak control."

Clinical • Journal