Safety and immunogenicity of rts,s+trap malaria vaccine, formulated in the as02a adjuvant system, in infant rhesus monkeys

Am J Trop Med Hyg. 2004 May;70(5):499-509.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Antibodies, Protozoan / blood
  • Female
  • Hepatitis B Surface Antigens / immunology*
  • Humans
  • Immunization
  • Interferon-gamma / biosynthesis
  • Interleukin-5 / biosynthesis
  • Lipid A / administration & dosage*
  • Lipid A / analogs & derivatives*
  • Lymphocyte Activation
  • Macaca mulatta
  • Malaria Vaccines / administration & dosage
  • Malaria Vaccines / immunology*
  • Malaria Vaccines / toxicity
  • Protozoan Proteins / immunology*
  • Saponins / administration & dosage*
  • Vaccines, Synthetic / immunology*
  • Vaccines, Synthetic / toxicity


  • Adjuvants, Immunologic
  • Antibodies, Protozoan
  • Hepatitis B Surface Antigens
  • Interleukin-5
  • Lipid A
  • Malaria Vaccines
  • Protozoan Proteins
  • Saponins
  • Vaccines, Synthetic
  • adjuvant SBAS-2
  • circumsporozoite protein, Protozoan
  • thrombospondin-related adhesive protein, protozoan
  • Interferon-gamma