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Infection and Immunity, June 2002, p. 2820-2827, Vol. 70, No. 6
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.6.2820-2827.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Regulation of Antigen-Specific Immunoglobulin G Subclasses in Response to Conserved and Polymorphic Plasmodium falciparum Antigens in an In Vitro Model

Olivier Garraud,^1* Ronald Perraut,¹ Ababacar Diouf,¹ Wilfrid S. Nambei,¹ Adama Tall,² André Spiegel,^2, Shirley Longacre,³ David C. Kaslow,^4, Hélène Jouin,³ Denise Mattei,⁵ Gina M. Engler,¹ Thomas B. Nutman,⁶ Eleanor M. Riley,⁷ and Odile Mercereau-Puijalon³

Laboratoire d'Immunologie,¹ Laboratoire d'Epidémiologie du Paludisme, Institut Pasteur de Dakar, Dakar, Senegal,² Unité d'Immunologie Moléculaire des Parasites,³ Unité de Biologie des Interactions Hôte-Parasite, Institut Pasteur, Paris, France,⁵ Malaria Vaccine Section,⁴ Helminth Immunology Section, Laboratory of Parasitie Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland,⁶ Department of Infectious and Tropical Diseases, The London School of Hygiene and Tropical Medicine, London, United Kingdom⁷

Received 11 November 2001/ Returned for modification 15 December 2001/ Accepted 25 February 2002

Cytophilic antibodies (Abs) play a critical role in protection against Plasmodium falciparum blood stages, yet little is known about the parameters regulating production of these Abs. We used an in vitro culture system to study the subclass distribution of antigen (Ag)-specific immunoglobulin G (IgG) produced by peripheral blood mononuclear cells (PBMCs) from individuals exposed to P. falciparum or unexposed individuals. PBMCs, cultivated with or without cytokines and exogenous CD40/CD40L signals, were stimulated with a crude parasite extract, recombinant vaccine candidates derived from conserved Ags (19-kDa C terminus of merozoite surface protein 1 [MSP1₁₉], R23, and PfEB200), or recombinant Ags derived from the polymorphic Ags MSP1 block 2 and MSP2. No P. falciparum-specific Ab production was detected in PBMCs from unexposed individuals. PBMCs from donors exposed frequently to P. falciparum infections produced multiple IgG subclasses when they were stimulated with the parasite extract but usually only one IgG subclass when they were stimulated with a recombinant Ag. Optimal Ab production required addition of interleukin-2 (IL-2) and IL-10 for all antigenic preparations. The IgG subclass distribution was both donor and Ag dependent and was only minimally influenced by the exogenous cytokine environment. In vitro IgG production and subclass distribution correlated with plasma Abs to some Ags (MSP1₁₉, R23, and MSP2) but not others (PfEB200 and the three MSP1 block 2-derived Ags). Data presented here suggest that intrinsic properties of the protein Ag itself play a major role in determining the subclass of the Ab response, which has important implications for rational design of vaccine delivery.

Editor: W. A. Petri, Jr.

Present address: Institut de Médecine Tropicale du Service de Santé des Armées, le Pharo, Marseille, France.

Present address: Vical, Inc., San Diego, Calif.

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