SAFETY AND IMMUNOGENICITY OF RTS,S+TRAP MALARIA VACCINE, FORMULATED IN THE AS02A ADJUVANT SYSTEM, IN INFANT RHESUS MONKEYS

DOUGLAS S. WALSH Departments of Immunology and Medicine, and Veterinary Medicine, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Departments of Pathology and Pediatrics, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva Medical School, Geneva, Switzerland; Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland; GlaxoSmithKline Biologicals, Rixensart, Belgium

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SATHIT PICHYANGKUL Departments of Immunology and Medicine, and Veterinary Medicine, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Departments of Pathology and Pediatrics, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva Medical School, Geneva, Switzerland; Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland; GlaxoSmithKline Biologicals, Rixensart, Belgium

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MONTIP GETTAYACAMIN Departments of Immunology and Medicine, and Veterinary Medicine, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Departments of Pathology and Pediatrics, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva Medical School, Geneva, Switzerland; Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland; GlaxoSmithKline Biologicals, Rixensart, Belgium

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PONGSRI TONGTAWE Departments of Immunology and Medicine, and Veterinary Medicine, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Departments of Pathology and Pediatrics, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva Medical School, Geneva, Switzerland; Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland; GlaxoSmithKline Biologicals, Rixensart, Belgium

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CLAIRE-ANNE SIEGRIST Departments of Immunology and Medicine, and Veterinary Medicine, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Departments of Pathology and Pediatrics, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva Medical School, Geneva, Switzerland; Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland; GlaxoSmithKline Biologicals, Rixensart, Belgium

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PRANEE HANSUKJARIYA Departments of Immunology and Medicine, and Veterinary Medicine, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Departments of Pathology and Pediatrics, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva Medical School, Geneva, Switzerland; Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland; GlaxoSmithKline Biologicals, Rixensart, Belgium

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KENT E. KESTER Departments of Immunology and Medicine, and Veterinary Medicine, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Departments of Pathology and Pediatrics, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva Medical School, Geneva, Switzerland; Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland; GlaxoSmithKline Biologicals, Rixensart, Belgium

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CAROLYN A. HOLLAND Departments of Immunology and Medicine, and Veterinary Medicine, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Departments of Pathology and Pediatrics, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva Medical School, Geneva, Switzerland; Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland; GlaxoSmithKline Biologicals, Rixensart, Belgium

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GERALD VOSS Departments of Immunology and Medicine, and Veterinary Medicine, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Departments of Pathology and Pediatrics, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva Medical School, Geneva, Switzerland; Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland; GlaxoSmithKline Biologicals, Rixensart, Belgium

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JOE COHEN Departments of Immunology and Medicine, and Veterinary Medicine, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Departments of Pathology and Pediatrics, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva Medical School, Geneva, Switzerland; Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland; GlaxoSmithKline Biologicals, Rixensart, Belgium

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ANN V. STEWART Departments of Immunology and Medicine, and Veterinary Medicine, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Departments of Pathology and Pediatrics, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva Medical School, Geneva, Switzerland; Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland; GlaxoSmithKline Biologicals, Rixensart, Belgium

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R. SCOTT MILLER Departments of Immunology and Medicine, and Veterinary Medicine, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Departments of Pathology and Pediatrics, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva Medical School, Geneva, Switzerland; Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland; GlaxoSmithKline Biologicals, Rixensart, Belgium

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W. RIPLEY BALLOU Departments of Immunology and Medicine, and Veterinary Medicine, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Departments of Pathology and Pediatrics, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva Medical School, Geneva, Switzerland; Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland; GlaxoSmithKline Biologicals, Rixensart, Belgium

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D. GRAY HEPPNER JR. Departments of Immunology and Medicine, and Veterinary Medicine, U.S. Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand; Departments of Pathology and Pediatrics, World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, University of Geneva Medical School, Geneva, Switzerland; Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland; GlaxoSmithKline Biologicals, Rixensart, Belgium

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DOI:
https://doi.org/10.4269/ajtmh.2004.70.499
Volume/Issue:
Volume 70: Issue 5
Page(s):
499–509
Restricted access
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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-γ 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.

Copyright:
Copyright 2004 The American Society of Tropical Medicine 2004
Received:
17 Nov 2003
|
Accepted:
19 Jan 2004
|
Published Online:
May 2004
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
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