Live Attenuated Malaria Vaccine Designed to Protect Through Hepatic CD8 + T Cell Immunity
Top Cited Papers
Open Access
- 28 October 2011
- journal article
- clinical trial
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 334 (6055), 475-480
- https://doi.org/10.1126/science.1211548
Abstract
Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8+ T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8+, IFN-γ–producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.Keywords
This publication has 66 references indexed in Scilit:
- Sterile Protective Immunity to Malaria is Associated with a Panel of Novel P. falciparum AntigensMolecular & Cellular Proteomics, 2011
- SPICE: Exploration and analysis of post‐cytometric complex multivariate datasetsCytometry Part A, 2011
- Safety and Immunogenicity of a Recombinant Nonglycosylated Erythrocyte Binding Antigen 175 Region II Malaria Vaccine in Healthy Adults Living in an Area Where Malaria Is Not EndemicClinical and Vaccine Immunology, 2010
- Poly(I:C) is an effective adjuvant for antibody and multi-functional CD4+ T cell responses to Plasmodium falciparum circumsporozoite protein (CSP) and αDEC-CSP in non human primatesVaccine, 2010
- Preerythrocytic, live-attenuated Plasmodium falciparum vaccine candidates by designProceedings of the National Academy of Sciences of the United States of America, 2009
- Randomized, Double‐Blind, Phase 2a Trial of Falciparum Malaria Vaccines RTS,S/AS01B and RTS,S/AS02A in Malaria‐Naive Adults: Safety, Efficacy, and Immunologic Associates of ProtectionThe Journal of Infectious Diseases, 2009
- Laboratory-based versus non-laboratory-based method for assessment of cardiovascular disease risk: the NHANES I Follow-up Study cohortThe Lancet, 2008
- Direct Microscopic Quantification of Dynamics of Plasmodium berghei Sporozoite Transmission from Mosquitoes to MiceInfection and Immunity, 2007
- Murine Immune Responses to Liver-Stage Antigen 1 Protein FMP011, a Malaria Vaccine Candidate, Delivered with Adjuvant AS01B or AS02AInfection and Immunity, 2007
- A proteomic view of the Plasmodium falciparum life cycleNature, 2002