Abstract
Heterologous prime-boost vaccination with chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) encoding multiple epitope string thrombospondin-related adhesion protein (ME-TRAP) has shown acceptable safety and promising immunogenicity in African adult and pediatric populations. If licensed, this vaccine could be given to infants receiving routine childhood immunizations. We therefore evaluated responses to ChAd63 MVA ME-TRAP when co-administered with routine Expanded Program on Immunization (EPI) vaccines. We enrolled 65 Gambian infants and neonates, aged 16, 8, or 1 week at first vaccination and randomized them to receive either ME-TRAP and EPI vaccines or EPI vaccines only. Safety was assessed by the description of vaccine-related adverse events (AEs). Immunogenicity was evaluated using IFNγ enzyme-linked immunospot, whole-blood flow cytometry, and anti-TRAP IgG ELISA. Serology was performed to confirm all infants achieved protective titers to EPI vaccines. The vaccines were well tolerated in all age groups with no vaccine-related serious AEs. High-level TRAP-specific IgG and T cell responses were generated after boosting with MVA. CD8+ T cell responses, previously found to correlate with protection, were induced in all groups. Antibody responses to EPI vaccines were not altered significantly. Malaria vectored prime-boost vaccines co-administered with routine childhood immunizations were well tolerated. Potent humoral and cellular immunity induced by ChAd63 MVA ME-TRAP did not reduce the immunogenicity of co-administered EPI vaccines, supporting further evaluation of this regimen in infant populations. The clinical trial was registered on http://Clinicaltrials.gov (NCT02083887) and the Pan-African Clinical Trials Registry (PACTR201402000749217).
Highlights
Recent estimates from the World Health Organization (WHO) show that many African countries are adopting preventive measures toward malaria elimination [1]
We investigated the safety and immunogenicity of chimpanzee adenovirus 63 (ChAd63) modified vaccinia virus Ankara (MVA) multiple epitope string thrombospondin-related adhesion protein (ME-TRAP) when co-administered with Expanded Program on Immunization (EPI) vaccines among Gambian infants aged 16, 8, and 1 week at first immunization
Following ChAd63 ME-TRAP coadministration with EPI vaccines in the 16-week-old cohort, fever was documented in similar numbers of infants (11/15, 73%) compared to the control (EPI vaccines only) group (80%, 4/5, p = 0.63 by Fisher’s exact test (FET)) (Table 2)
Summary
Recent estimates from the World Health Organization (WHO) show that many African countries are adopting preventive measures toward malaria elimination [1]. Novel approaches to generate immunity to malaria employing viral vector vaccines were initially limited due to the use of homologous prime-boost approaches that induced relatively poor T cell responses [5, 6] These have been improved by the development of a novel heterologous approach, which elicits potent and durable cell-mediated immunity [7]. Heterologous prime-boost vaccination with chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) encoding multiple epitope string thrombospondin-related adhesion protein (ME-TRAP) has shown acceptable safety and promising immunogenicity in African adult and pediatric populations. If licensed, this vaccine could be given to infants receiving routine childhood immunizations. We evaluated responses to ChAd63 MVA ME-TRAP when co-administered with routine Expanded Program on Immunization (EPI) vaccines
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