title: Safety and immunogenicity of rts,s+trap malaria vaccine, formulated in the as02a adjuvant system, in infant rhesus monkeys.
abstract: Malaria vaccine RTS,S combined with thrombospondin-related anonymous protein (TRAP) and formulated with AS02A (RTS,S+TRAP/AS02A) is safe and immunogenic in adult humans and rhesus monkeys (Macaca mulatta). Here, RTS,S+TRAP/AS02A was administered on a 0-, 1-, and 3-month schedule to three cohorts of infant monkeys, along with adult comparators. Cohort 1 evaluated 1/5, 1/2, and full adult doses, with the first dose administration at one month of age; cohort 2 monkeys received full adult doses, with the first dose administration at one versus three months of age; and, cohort 3 compared infants gestated in mothers with or without previous RTS,S/AS02A immunization. Immunization site reactogenicity was mild. Some infants, including the phosphate-buffered saline only recipient, developed transient iron-deficiency anemia, which is considered a result of repeated phlebotomies. All RTS,S+TRAP/AS02A regimens induced vigorous antibody responses that persisted through 12 weeks after the last vaccine dose. Modest lymphoproliferative and ELISPOT (interferon-gamma and interleukin-5) responses, particularly to TRAP, approximated adult comparators. RTS,S+TRAP/AS02A was safe and well tolerated. Vigorous antibody production and modest, selective cell-mediated immune responses suggest that RTS,S+TRAP/AS02A may be immunogenic in human infants.
authors.affiliation: Department of Immunology and Medicine, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. douglas.walsh@se.amedd.army.mil
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Walsh
authors.forename: Sathit
authors.initials: S
authors.lastname: Pichyangkul
authors.forename: Montip
authors.initials: M
authors.lastname: Gettayacamin
authors.forename: Pongsri
authors.initials: P
authors.lastname: Tongtawe
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Siegrist
authors.forename: Pranee
authors.initials: P
authors.lastname: Hansukjariya
authors.forename: Kent E
authors.initials: KE
authors.lastname: Kester
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Holland
authors.forename: Gerald
authors.initials: G
authors.lastname: Voss
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Ann V
authors.initials: AV
authors.lastname: Stewart
authors.forename: R Scott
authors.initials: RS
authors.lastname: Miller
authors.forename: W Ripley
authors.initials: WR
authors.lastname: Ballou
authors.forename: D Gray
authors.initials: DG
authors.lastname: Heppner
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008050:Lipid A / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity; D015800:Protozoan Proteins / Q000276:immunology*; D012503:Saponins / Q000008:administration & dosage*; D014614:Vaccines, Synthetic / Q000276:immunology* / Q000633:toxicity
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D006514:Hepatitis B Surface Antigens; D015848:Interleukin-5; D008050:Lipid A; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D012503:Saponins; D014614:Vaccines, Synthetic; C472719:adjuvant SBAS-2; C041595:circumsporozoite protein, Protozoan; C069428:thrombospondin-related adhesive protein, protozoan; D007371:Interferon-gamma