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English

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

Contributors

Walsh, Douglas S; Pichyangkul, Sathit; Gettayacamin, Montip; Tongtawe, Pongsri; Siegrist, Claire-Anne; Hansukjariya, Pranee; Kester, Kent E; Holland, Carolyn A; Voss, Gerald; Cohen, Joe; Stewart, Ann V; Miller, R Scott; Ballou, W Ripley; Heppner, D Gray (Jr)

Published in

The American journal of tropical medicine and hygiene, vol. 70, no. 5, p. 499-509

Publication date

2004

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.

Keywords

  • 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/analogs & derivatives
  • Lymphocyte Activation
  • Macaca mulatta
  • Malaria Vaccines/administration & dosage/immunology/toxicity
  • Protozoan Proteins/immunology
  • Saponins/administration & dosage
  • Vaccines, Synthetic/immunology/toxicity

UNIGE affiliation entities

UNIGE research groups

Citation (ISO format)

WALSH, Douglas S et al. Safety and immunogenicity of rts,s+trap malaria vaccine, formulated in the as02a adjuvant system, in infant rhesus monkeys. In: The American journal of tropical medicine and hygiene, 2004, vol. 70, n° 5, p. 499–509.

Main files (1)

Article (Published version)

Identifiers

Additional URL for this publication

http://www.ajtmh.org/content/70/5/499.long

Journal ISSN

0002-9637
995views
1303downloads

Technical informations

Creation

26/02/2015 13:33:00

First validation

26/02/2015 13:33:00

Update

14/03/2023 23:09:29

Status update

14/03/2023 23:09:28

Last indexation

30/10/2024 23:51:32
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