Trends in Immunology
Malaria-specific antibody subclasses in immune individuals: a key source of information for vaccine design
Section snippets
Epidemiological support for antibody-mediated protection
Infection by P. falciparum is complex, as shown by the parasite life cycle (Fig. 1). Blood-stage infection, which accounts for the majority of morbidity and mortality, generates a protective response in most individuals exposed repeatedly to the parasite. The acquisition of this type of natural protection is labile and is dependent on the intensity, length and duration of an individual's exposure to the parasite [1]. In general, adults living in areas where transmission is at least mesoendemic
Relationship between IgG subclass properties and mechanisms of antibody-mediated protection
Not only are antibodies markers of infection but they are also effectors of protection in many infectious circumstances. There is good in vivo evidence that antibodies can mediate protection against the blood stage of P. falciparum [14]. Protective IgG antibodies belong to a restricted panel of subclasses, specifically IgG1 and IgG3, whereas IgG4 antibodies are considered nonprotective 15, 16, 17, 18. IgE antibodies have been associated with pathology [19] and no specific function has been
Balances in isotype production and use of antibodies in malaria
To develop better models to explain anti-malarial antibody responses, it is proposed that antibody levels detectable in the plasma or serum of P. falciparum-immune individuals result from a balance between production and use of parasite-specific antibodies. In naturally immune adults, anti-MSP119 IgG1 and IgG3 antibodies appeared to evolve with the seasons, in a manner strongly dependent on the parasite burden in the villages under study, and it was shown that specific IgG1 versus IgG3
In vitro selection of IgG subclasses against malaria antigens
In parallel, several groups 47, 48, 49 have carried out studies in B-cell culture systems using B cells obtained from the blood of individual immune donors. These B cells could differentiate in vitro to produce antibodies of diverse classes/subclasses on in vitro (re)-stimulation either with crude extracts (multiple antigens) of P. falciparum or defined, purified antigens. Sensitized B cells [47] from almost every P. falciparum-immune donor produced all four isotypes of antibodies in vitro when
From the field and towards a vaccine
Blood-stage P. falciparum malaria is a unique example of an infection in which individuals exposed repeatedly to the pathogen acquire immunity and demonstrate definite evidence of cellular and humoral effectors. It is tempting to speculate that, in this infection more than in most, a first ‘wave’ of antibody responses with multiple classes/subclasses is followed by the sustained boosting of the immune system with parasite antigens towards a second ‘wave’ of antibody responses with one or two
Acknowledgements
We are grateful to present and former colleagues and collaborators at the Institut Pasteur in Paris, Dakar (Senegal) and Cayenne (French Guiana) for their respective contribution to the malaria studies. We also acknowledge present and former colleagues at the IRD (ex-ORSTOM) in Dakar, at the departments of Immunology and Parasitology at the University Medical School, University Cheikh Anta Diop in Dakar, and to the villagers of Dielmo and Ndiop (Senegal). This work has received constant support
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