title: Discovery of Novel Plasmodium falciparum Pre-Erythrocytic Antigens for Vaccine Development.
abstract: BACKGROUND
  Nearly 100% protection against malaria infection can be achieved in humans by immunization with P. falciparum radiation-attenuated sporozoites (RAS). Although it is thought that protection is mediated by T cell and antibody responses, only a few of the many pre-erythrocytic (sporozoite and liver stage) antigens that are targeted by these responses have been identified.
  
  
  METHODS
  Twenty seven P. falciparum pre-erythrocytic antigens were selected using bioinformatics analysis and expression databases and were expressed in a wheat germ cell-free protein expression system. Recombinant proteins were recognized by plasma from RAS-immunized subjects, and 21 induced detectable antibody responses in mice and rabbit and sera from these immunized animals were used to characterize these antigens. All 21 proteins localized to the sporozoite: five localized to the surface, seven localized to the micronemes, cytoplasm, endoplasmic reticulum or nucleus, two localized to the surface and cytoplasm, and seven remain undetermined. PBMC from RAS-immunized volunteers elicited positive ex vivo or cultured ELISpot responses against peptides from 20 of the 21 antigens.
  
  
  CONCLUSIONS
  These T cell and antibody responses support our approach of using reagents from RAS-immunized subjects to screen potential vaccine antigens, and have led to the identification of a panel of novel P. falciparum antigens. These results provide evidence to further evaluate these antigens as vaccine candidates.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00870987 ClinicalTrials.gov NCT00392015.
authors: Malaria Department, Naval Medical Research Center, Silver Spring, MD 20910, United States of America; Camris International, Bethesda, MD 20814, United States of America.
authors: Joao C
authors: JC
authors: Aguiar
authors: Malaria Department, Naval Medical Research Center, Silver Spring, MD 20910, United States of America; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, United States of America.
authors: Jessica
authors: J
authors: Bolton
authors: Malaria Department, Naval Medical Research Center, Silver Spring, MD 20910, United States of America; Technical Resources International, Inc., Bethesda, MD 20817, United States of America.
authors: Joyce
authors: J
authors: Wanga
authors: Department of Microbiology and Immunology, The University of Maryland School of Medicine, Baltimore, MD 21201, United States of America.
authors: John B
authors: JB
authors: Sacci
authors: Department of International Health, Kobe University Graduate School of Health Science, Kobe 654-0142, Japan.
authors: Hideyuki
authors: H
authors: Iriko
authors: Malaria Department, Naval Medical Research Center, Silver Spring, MD 20910, United States of America; EMD Millipore Corporation, North Andover, MA 01845, United States of America.
authors: Julie K
authors: JK
authors: Mazeika
authors: Department of Medical Environmental Biology and Tropical Medicine, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do 200-701, Republic of Korea.
authors: Eun-Taek
authors: ET
authors: Han
authors: Malaria Department, Naval Medical Research Center, Silver Spring, MD 20910, United States of America; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, United States of America.
authors: Keith
authors: K
authors: Limbach
authors: Malaria Department, Naval Medical Research Center, Silver Spring, MD 20910, United States of America; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, United States of America.
authors: Noelle B
authors: NB
authors: Patterson
authors: Malaria Department, Naval Medical Research Center, Silver Spring, MD 20910, United States of America.
authors: Martha
authors: M
authors: Sedegah
authors: PATH Malaria Vaccine Initiative, Washington, DC 20001, United States of America.
authors: Ann-Marie
authors: AM
authors: Cruz
authors: Proteo-Science Center, Ehime University, Matsuyama, Ehime 790-8577, Japan.
authors: Takafumi
authors: T
authors: Tsuboi
authors: Malaria Department, Naval Medical Research Center, Silver Spring, MD 20910, United States of America.
authors: Stephen L
authors: SL
authors: Hoffman
authors: Malaria Department, Naval Medical Research Center, Silver Spring, MD 20910, United States of America.
authors: Daniel
authors: D
authors: Carucci
authors: Malaria Department, Naval Medical Research Center, Silver Spring, MD 20910, United States of America; The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, United States of America.
authors: Michael R
authors: MR
authors: Hollingdale
authors: Malaria Department, Naval Medical Research Center, Silver Spring, MD 20910, United States of America.
authors: Eileen D
authors: ED
authors: Villasante
authors: Malaria Department, Naval Medical Research Center, Silver Spring, MD 20910, United States of America.
authors: Thomas L
authors: TL
authors: Richie
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology* / Q000469:parasitology; D006801:Humans; D007114:Immunization; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000469:parasitology; D017780:Malaria Vaccines / Q000276:immunology* / Q000494:pharmacology; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology; D011817:Rabbits; D034101:Sporozoites / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000469:parasitology
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins