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Safety and Immunogenicity of ChAd63 and MVA ME-TRAP in West African Children and Infants.

ABSTRACT: Malaria remains a significant global health burden and a vaccine would make a substantial contribution to malaria control. Chimpanzee Adenovirus 63 Modified Vaccinia Ankara Multiple epitope thrombospondin adhesion protein (ME-TRAP) and vaccination has shown significant efficacy against malaria sporozoite challenge in malaria-naive European volunteers and against malaria infection in Kenyan adults. Infants are the target age group for malaria vaccination; however, no studies have yet assessed T-cell responses in children and infants. We enrolled 138 Gambian and Burkinabe children in four different age-groups: 2-6 years old in The Gambia; 5-17 months old in Burkina Faso; 5-12 months old, and also 10 weeks old, in The Gambia; and evaluated the safety and immunogenicity of Chimpanzee Adenovirus 63 Modified Vaccinia Ankara ME-TRAP heterologous prime-boost immunization. The vaccines were well tolerated in all age groups with no vaccine-related serious adverse events. T-cell responses to vaccination peaked 7 days after boosting with Modified Vaccinia Ankara, with T-cell responses highest in 10 week-old infants. Heterologous prime-boost immunization with Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara ME-TRAP was well tolerated in infants and children, inducing strong T-cell responses. We identify an approach that induces potent T-cell responses in infants, which may be useful for preventing other infectious diseases requiring cellular immunity.

SUBMITTER: Afolabi MO

PROVIDER: S-EPMC5010143 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Safety and Immunogenicity of ChAd63 and MVA ME-TRAP in West African Children and Infants.

Afolabi Muhammed O MO Tiono Alfred B AB Adetifa Uche J UJ Yaro Jean Baptiste JB Drammeh Abdoulie A Nébié Issa I Bliss Carly C Hodgson Susanne H SH Anagnostou Nicholas A NA Sanou Guillaume S GS Jagne Ya Jankey YJ Ouedraogo Oumarou O Tamara Casimir C Ouedraogo Nicolas N Ouedraogo Mirielle M Njie-Jobe Jainaba J Diarra Amidou A Duncan Christopher Ja CJ Cortese Riccardo R Nicosia Alfredo A Roberts Rachel R Viebig Nicola K NK Leroy Odile O Lawrie Alison M AM Flanagan Katie L KL Kampman Beate B Bejon Philip P Imoukhuede Egeruan B EB Ewer Katie J KJ Hill Adrian Vs AV Bojang Kalifa K Sirima Sodiomon B SB

Molecular therapy : the journal of the American Society of Gene Therapy 20160425 8

Malaria remains a significant global health burden and a vaccine would make a substantial contribution to malaria control. Chimpanzee Adenovirus 63 Modified Vaccinia Ankara Multiple epitope thrombospondin adhesion protein (ME-TRAP) and vaccination has shown significant efficacy against malaria sporozoite challenge in malaria-naive European volunteers and against malaria infection in Kenyan adults. Infants are the target age group for malaria vaccination; however, no studies have yet assessed T-c ...[more]

PMID: 27109630

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Project description:Malaria transmission is in decline in some parts of Africa, partly due to the scaling up of control measures. If the goal of elimination is to be achieved, additional control measures including an effective and durable vaccine will be required. Studies utilising the prime-boost approach to deliver viral vectors encoding the pre-erythrocytic antigen ME-TRAP (multiple epitope thrombospondin-related adhesion protein) have shown promising safety, immunogenicity and efficacy in sporozoite challenge studies. More recently, a study in Kenyan adults, similar to that reported here, showed substantial efficacy against P. falciparum infection. One hundred and twenty healthy male volunteers, living in a malaria endemic area of Senegal were randomised to receive either the Chimpanzee adenovirus (ChAd63) ME-TRAP as prime vaccination, followed eight weeks later by modified vaccinia Ankara (MVA) also encoding ME-TRAP as booster, or two doses of anti-rabies vaccine as a comparator. Prior to follow-up, antimalarials were administered to clear parasitaemia and then participants were monitored by PCR for malaria infection for eight weeks. The primary endpoint was time-to-infection with P. falciparum malaria, determined by two consecutive positive PCR results. Secondary endpoints included adverse event reporting, measures of cellular and humoral immunogenicity and a meta-analysis of combined vaccine efficacy with the parallel study in Kenyan adults.We show that this pre-erythrocytic malaria vaccine is safe and induces significant immunogenicity, with a peak T-cell response at seven days after boosting of 932 Spot Forming Cells (SFC)/106 Peripheral Blood Mononuclear Cells(PBMC) compared to 57 SFC/ 106 PBMCs in the control group. However, a vaccine efficacy was not observed: 12 of 57 ME-TRAP vaccinees became PCR positive during the intensive monitoring period as compared to 13 of the 58 controls (P = 0.80). This trial confirms that vaccine efficacy against malaria infection in adults may be rapidly assessed using this efficient and cost-effective clinical trial design. Further efficacy evaluation of this vectored candidate vaccine approach in other malaria transmission settings and age-de-escalation into the main target age groups for a malaria vaccine is in progress.

Dataset Information

Safety and Immunogenicity of ChAd63 and MVA ME-TRAP in West African Children and Infants.

Publications

Safety and Immunogenicity of ChAd63 and MVA ME-TRAP in West African Children and Infants.

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