Nature. 2017 Feb 23;542(7642):445-449
Authors
Benjamin Mordmüller, Güzin Surat, Heimo Lagler, Sumana Chakravarty, Andrew S. Ishizuka, Albert Lalremruata, Markus Gmeiner, Joseph J. Campo, Meral Esen, Adam J. Ruben, Jana Held, Carlos Lamsfus Calle, Juliana B. Mengue, Tamirat Gebru, Javier Ibáñez, Mihály Sulyok, Eric R. James, Peter F. Billingsley, Natasha KC, Anita Manoj, Tooba Murshedkar, Anusha Gunasekera, Abraham G. Eappen, Tao Li, Richard E. Stafford, Minglin Li, Phil L. Felgner, Robert A. Seder, Thomas L. Richie, B. Kim Lee Sim, Stephen L. Hoffman and Peter G. Kremsner
Abstract
A highly protective malaria vaccine would greatly facilitate the prevention and elimination of malaria and containment of drugresistant parasites1. A high level (more than 90%) of protection against malaria in humans has previously been achieved only by immunization with radiation-attenuated Plasmodium falciparum (Pf ) sporozoites (PfSPZ) inoculated by mosquitoes2–4; by intravenous injection of aseptic, purified, radiation-attenuated, cryopreserved PfSPZ (‘PfSPZ Vaccine’)5,6; or by infectious PfSPZ inoculated by mosquitoes to volunteers taking chloroquine7–10 or mefloquine11 (chemoprophylaxis with sporozoites). We assessed immunization by direct venous inoculation of aseptic, purified, cryopreserved, non-irradiated PfSPZ (‘PfSPZ Challenge’12,13) to malaria-naive, healthy adult volunteers taking chloroquine for antimalarial chemoprophylaxis (vaccine approach denoted as PfSPZCVac) 14. Three doses of 5.12 × 104 PfSPZ of PfSPZ Challenge12,13 at 28-day intervals were well tolerated and safe, and prevented infection in 9 out of 9 (100%) volunteers who underwent controlled human malaria infection ten weeks after the last dose (group III). Protective efficacy was dependent on dose and regimen. Immunization with 3.2 × 103 (group I) or 1.28 × 104 (group II) PfSPZ protected 3 out of 9 (33%) or 6 out of 9 (67%) volunteers, respectively. Three doses of 5.12 × 104 PfSPZ at five-day intervals protected 5 out of 8 (63%) volunteers. The frequency of Pf-specific polyfunctional CD4 memory T cells was associated with protection. On a 7,455 peptide Pf proteome array, immune sera from at least 5 out of 9 group III vaccinees recognized each of 22 proteins. PfSPZ-CVac is a highly efficacious vaccine candidate; when we are able to optimize the immunization regimen (dose, interval between doses, and drug partner), this vaccine could be used for combination mass drug administration and a mass vaccination program approach to eliminate malaria from geographically defined areas.