First field efficacy trial of the ChAd63 MVA ME-TRAP vectored malaria vaccine candidate in 5-17 months old infants and children

Alfred B Tiono, Issa Nébié, Nicholas Anagnostou, Aboubacar S Coulibaly, Georgina Bowyer, Erika Lam, Edith C Bougouma, Alphonse Ouedraogo, Jean Baptist B Yaro, Aïssata Barry, Rachel Roberts, Tommy Rampling, Carly Bliss, Susanne Hodgson, Alison Lawrie, Amidou Ouedraogo, Egeruan Babatunde Imoukhuede, Katie J Ewer, Nicola K Viebig, Amidou Diarra, Odile Leroy, Philip Bejon, Adrian V S Hill, Sodiomon B Sirima, Alfred B Tiono, Issa Nébié, Nicholas Anagnostou, Aboubacar S Coulibaly, Georgina Bowyer, Erika Lam, Edith C Bougouma, Alphonse Ouedraogo, Jean Baptist B Yaro, Aïssata Barry, Rachel Roberts, Tommy Rampling, Carly Bliss, Susanne Hodgson, Alison Lawrie, Amidou Ouedraogo, Egeruan Babatunde Imoukhuede, Katie J Ewer, Nicola K Viebig, Amidou Diarra, Odile Leroy, Philip Bejon, Adrian V S Hill, Sodiomon B Sirima

Abstract

Background: Heterologous prime boost immunization with chimpanzee adenovirus 63 (ChAd63) and Modified Vaccinia Virus Ankara (MVA) vectored vaccines is a strategy previously shown to provide substantial protective efficacy against P. falciparum infection in United Kingdom adult Phase IIa sporozoite challenge studies (approximately 20-25% sterile protection with similar numbers showing clear delay in time to patency), and greater point efficacy in a trial in Kenyan adults.

Methodology: We conducted the first Phase IIb clinical trial assessing the safety, immunogenicity and efficacy of ChAd63 MVA ME-TRAP in 700 healthy malaria exposed children aged 5-17 months in a highly endemic malaria transmission area of Burkina Faso.

Results: ChAd63 MVA ME-TRAP was shown to be safe and immunogenic but induced only moderate T cell responses (median 326 SFU/106 PBMC (95% CI 290-387)) many fold lower than in previous trials. No significant efficacy was observed against clinical malaria during the follow up period, with efficacy against the primary endpoint estimate by proportional analysis being 13.8% (95%CI -42.4 to 47.9) at sixth month post MVA ME-TRAP and 3.1% (95%CI -15.0 to 18.3; p = 0.72) by Cox regression.

Conclusions: This study has confirmed ChAd63 MVA ME-TRAP is a safe and immunogenic vaccine regimen in children and infants with prior exposure to malaria. But no significant protective efficacy was observed in this very highly malaria-endemic setting.

Trial registration: ClinicalTrials.gov NCT01635647. Pactr.org PACTR201208000404131.

Conflict of interest statement

AVSH is a named inventor on patent applications and issued patents relating to malaria vectored vaccines and immunization regimes. This does not alter the author’s adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Trial profile.
Fig 1. Trial profile.
Fig 2. Incidence of local solicited adverse…
Fig 2. Incidence of local solicited adverse events in trial participants.
(A) Local AEs post ChAd63 ME-TRAP vs. Rabies. (B) Local AEs post MVA ME-TRAP vs. Rabies.
Fig 3. Incidence of solicited systemic adverse…
Fig 3. Incidence of solicited systemic adverse events in trial participants.
(A) Solicited systemic AEs post ChAd63 ME-TRAP vs. Rabies. (B) Solicited systemic AEs post MVA ME-TRAP vs. Rabies.
Fig 4. IFN-γ ELISPOT responses to ChAd63…
Fig 4. IFN-γ ELISPOT responses to ChAd63 MVA ME-TRAP.
A total of 169 children were part of a nested cohort randomly selected by the study statistician for the IFN-γ ELISPOT responses evaluation (A) represents the responses at baseline and 7 days post MVA ME-TRAP and (B) the responses at day 63 according to age categories.
Fig 5. Anti-TRAP IgG titers.
Fig 5. Anti-TRAP IgG titers.
(A). Antibody responses to TRAP at baseline, after priming with ChAd63 ME-TRAP (D28) and boosting with MVA ME-TRAP (D63), n = 169, ****p<0.0001, Kruskal-Wallis test. (B) Antibody responses at baseline and after second vaccination in the rabies and ME-TRAP vaccinees, (****p<0.0001, Mann-Whitney test). (C)Increased antibody titers in female participants after boosting with MVA ME-TRAP, **p<0.004, Mann-Whitney test. (D) Increased antibody titers after boosting in the 5–8 months old female children, p = 0.03, Mann-Whitney test.
Fig 6. Protective efficacy against clinical malaria…
Fig 6. Protective efficacy against clinical malaria of ME-TRAP by Kaplan Meier analysis.
Fig 7. Protective efficacy against severe malaria…
Fig 7. Protective efficacy against severe malaria of ME-TRAP by Kaplan Meier analysis.

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