Safety and immunogenicity of rts,s+trap malaria vaccine, formulated in the as02a adjuvant system, in infant rhesus monkeys.
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.
Walsh
Douglas S
DS
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
Pichyangkul
Sathit
S
Gettayacamin
Montip
M
Tongtawe
Pongsri
P
Siegrist
Claire-Anne
CA
Hansukjariya
Pranee
P
Kester
Kent E
KE
Holland
Carolyn A
CA
Voss
Gerald
G
Cohen
Joe
J
Stewart
Ann V
AV
Miller
R Scott
RS
Ballou
W Ripley
WR
Heppner
D Gray
DG
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
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