AUTHOR=Mensah Victorine A. , Roetynck Sophie , Kanteh Ebrima K. , Bowyer Georgina , Ndaw Amy , Oko Francis , Bliss Carly M. , Jagne Ya Jankey , Cortese Riccardo , Nicosia Alfredo , Roberts Rachel , D’Alessio Flavia , Leroy Odile , Faye Babacar , Kampmann Beate , Cisse Badara , Bojang Kalifa , Gerry Stephen , Viebig Nicola K. , Lawrie Alison M. , Clarke Ed , Imoukhuede Egeruan B. , Ewer Katie J. , Hill Adrian V. S. , Afolabi Muhammed O. 

TITLE=Safety and Immunogenicity of Malaria Vectored Vaccines Given with Routine Expanded Program on Immunization Vaccines in Gambian Infants and Neonates: A Randomized Controlled Trial

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01551

DOI=10.3389/fimmu.2017.01551

ISSN=1664-3224

ABSTRACT=<sec id="ST1"><title>Background</title><p>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.</p></sec><sec id="ST2"><title>Methods</title><p>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.</p></sec><sec id="ST3"><title>Results</title><p>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<sup>+</sup> T cell responses, previously found to correlate with protection, were induced in all groups. Antibody responses to EPI vaccines were not altered significantly.</p></sec><sec id="ST4"><title>Conclusion</title><p>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.</p></sec><sec id="ST5"><title>Clinical Trial Registration</title><p>The clinical trial was registered on <uri xlink:href="http://Clinicaltrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">http://Clinicaltrials.gov</uri> (NCT02083887) and the Pan-African Clinical Trials Registry (PACTR201402000749217).</p></sec>