@article{10.1172/jci.insight.96381, author = {Ruth O. Payne AND Sarah E. Silk AND Sean C. Elias AND Kazutoyo Miura AND Ababacar Diouf AND Francis Galaway AND Hans de Graaf AND Nathan J. Brendish AND Ian D. Poulton AND Oliver J. Griffiths AND Nick J. Edwards AND Jing Jin AND Geneviève M. Labbé AND Daniel G.W. Alanine AND Loredana Siani AND Stefania Di Marco AND Rachel Roberts AND Nicky Green AND Eleanor Berrie AND Andrew S. Ishizuka AND Carolyn M. Nielsen AND Martino Bardelli AND Frederica D. Partey AND Michael F. Ofori AND Lea Barfod AND Juliana Wambua AND Linda M. Murungi AND Faith H. Osier AND Sumi Biswas AND James S. McCarthy AND Angela M. Minassian AND Rebecca Ashfield AND Nicola K. Viebig AND Fay L. Nugent AND Alexander D. Douglas AND Johan Vekemans AND Gavin J. Wright AND Saul N. Faust AND Adrian V.S. Hill AND Carole A. Long AND Alison M. Lawrie AND Simon J. Draper}, journal = {JCI Insight}, publisher = {The American Society for Clinical Investigation}, title = {Human vaccination against RH5 induces neutralizing antimalarial antibodies that inhibit RH5 invasion complex interactions}, year = {2017}, month = {11}, volume = {2}, url = {https://insight.jci.org/articles/view/96381}, abstract = {The development of a highly effective vaccine remains a key strategic goal to aid the control and eventual eradication of Plasmodium falciparum malaria. In recent years, the reticulocyte-binding protein homolog 5 (RH5) has emerged as the most promising blood-stage P. falciparum candidate antigen to date, capable of conferring protection against stringent challenge in Aotus monkeys. We report on the first clinical trial to our knowledge to assess the RH5 antigen — a dose-escalation phase Ia study in 24 healthy, malaria-naive adult volunteers. We utilized established viral vectors, the replication-deficient chimpanzee adenovirus serotype 63 (ChAd63), and the attenuated orthopoxvirus modified vaccinia virus Ankara (MVA), encoding RH5 from the 3D7 clone of P. falciparum. Vaccines were administered i.m. in a heterologous prime-boost regimen using an 8-week interval and were well tolerated. Vaccine-induced anti-RH5 serum antibodies exhibited cross-strain functional growth inhibition activity (GIA) in vitro, targeted linear and conformational epitopes within RH5, and inhibited key interactions within the RH5 invasion complex. This is the first time to our knowledge that substantial RH5-specific responses have been induced by immunization in humans, with levels greatly exceeding the serum antibody responses observed in African adults following years of natural malaria exposure. These data support the progression of RH5-based vaccines to human efficacy testing.}, number = {21}, doi = {10.1172/jci.insight.96381}, url = {https://doi.org/10.1172/jci.insight.96381}, }