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Infection and Immunity, October 2009, p. 4502-4509, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00442-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Plasmodium falciparum-Specific Cellular Immune Responses after Immunization with the RTS,S/AS02D Candidate Malaria Vaccine in Infants Living in an Area of High Endemicity in Mozambique {triangledown}

Arnoldo Barbosa,1,2 Denise Naniche,2 John J. Aponte,1,2 M. Nelia Manaca,1 Inacio Mandomando,1,4 Pedro Aide,1,4 Jahit Sacarlal,3 Montse Renom,1,2 Sarah Lafuente,1,2 W. Ripley Ballou,5 and Pedro L. Alonso1,2*

Centro de Investigação en Saúde de Manhiça, Manhiça, Mozambique,1 Barcelona Centre for International Health Research, Hospital Clinic/Institut d'Investigacions Biomediques August Pi i Sunyer, Universitat de Barcelona, Barcelona, Spain,2 Facultade de Medicina, Universidade Eduardo Mondlane, Maputo, Mozambique,3 National Institute of Health, Ministry of Health, Maputo, Mozambique,4 GlaxoSmithKline Biologicals, Rixensart, Belgium5

Received 20 April 2009/ Returned for modification 6 June 2009/ Accepted 23 July 2009

Results from clinical trials in areas where malaria is endemic have shown that immunization with RTS,S/AS02A malaria vaccine candidate induces partial protection in adults and children and cellular effector and memory responses in adults. For the first time in a malaria vaccine trial, we sought to assess the cell-mediated immune responses to RTS,S antigen components in infants under 1 year of age participating in a clinical phase I/IIb trial of RTS,S/AS02D in Mozambique. Circumsporozoite protein (CSP)-specific responses were detected in approximately half of RTS,S-immunized infants and included gamma interferon (IFN-{gamma}), interleukin-2 (IL-2), and combined IL-2/IL-4 responses. The median stimulation indices of cytokine-producing CD4+ and CD8+ cells were very low but significantly higher in RTS,S-immunized infants than in infants that received the comparator vaccine. Protection against subsequent malarial infection tended to be associated with a higher percentage of individuals with CSP-specific IL-2 in the supernatant (P = 0.053) and with higher CSP-specific IFN-{gamma}-producing CD8+ T-cell responses (P = 0.07). These results report for the first time the detection of malaria-specific cellular immune responses after vaccination of infants less than 1 year of age and pave the way for future field studies of cellular immunity to malaria vaccine candidates.

* Corresponding author. Mailing address: Barcelona Centre for International Health Research (CRESIB), Hospital Clinic/IDIBAPS, C. Rossello 132, 4°, 2>>, Barcelona 08036, Spain. Phone: (34) 93 227 5706. Fax: (34) 93 227 9853. E-mail: palonso{at}clinic.ub.es

{triangledown} Published ahead of print on 3 August 2009.

Editor: W. A. Petri, Jr.

Infection and Immunity, October 2009, p. 4502-4509, Vol. 77, No. 10
0019-9567/09/$08.00+0     doi:10.1128/IAI.00442-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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