Acquisition of antibody isotypes against Plasmodium falciparum blood stage antigens in a birth cohort

Abstract

Information on the period during which infants lose their maternally derived antibodies to malaria and begin to acquire naturally their own immune responses against parasite antigens is crucial for understanding when malaria vaccines may be best administered. This study investigated the rates of decline and acquisition of serum antibody isotypes IgG1, IgG2, IgG3, IgG4, IgM and IgA to Plasmodium falciparum antigens apical membrane antigen (AMA1), merozoite surface proteins (MSP1-19, MSP2 and MSP3) in a birth cohort of 53 children living in an urban area in the Gambia, followed over the first 3 years of life (sampled at birth, 4, 9, 18 and 36 months). Antigen-specific maternally transferred antibody isotypes of all IgG subclasses were detected at birth and were almost totally depleted by 4 months of age. Acquisition of specific antibody isotypes to the antigens began with IgM, followed by IgG1 and IgA. Against the MSP2 antigen, IgG1 but not IgG3 responses were observed in the children, in contrast with the maternally derived antibodies to this antigen that were mostly IgG3. This confirms that IgG subclass responses to MSP2 are strongly dependent on age or previous malaria experience, polarized towards IgG1 early in life and to IgG3 in older exposed individuals.

Figure 1

The mean OD and SE of cord blood plasma antibody isotype reactivities to antigens for children in each birth month (July, n = 5; August, n = 15; September, n = 17; January, n = 7; February, n = 9). Serum dilutions used for the detection of IgG subclasses are indicated in brackets in the graph (1/500 for IgG1 and IgG3, 1/50 for IgG2 and IgG4).

Figure 2

Proportion of children with positive reactivities of antibody isotypes IgG1, IgG2, IgG3, IgG4, IgM and IgA to antigens at ages 0, 4, 9, 18 and 36 months. Each line represents the change in proportions of children with positive reactivities (ELISA OD >mean + 3 SD of negative control sera panel) against specific antigens at different ages.

Figure 3

The decline and acquisition of the antibody isotypes, IgG1, IgG2, IgG3, IgG4, IgM and IgA, to AMA1 over the five time points 0, 4, 9, 18 and 36 months. Each line represents the measurement of antibody levels in an individual at different ages.

Figure 4

The decline and acquisition of the antibody isotypes, IgG1, IgG2, IgG3, IgG4, IgM and IgA, to MSP1-19 over the five time points 0, 4, 9, 18 and 36 months. Each line represents the measurement of antibody levels in an individual at different ages.

Figure 5

(a) The decline and acquisition of the antibody isotypes, IgG1, IgG2, IgG3, IgG4, IgM and IgA, to MSP3-3D7 over the five time points 0, 4, 9, 18 and 36 months. Each line represents the measurement of antibody levels in an individual at different ages. (b) The decline and acquisition of the antibody isotypes, IgG1, IgG2, IgG3, IgG4, IgM and IgA, to MSP3-K1 over the five time points 0, 4, 9, 18 and 36 months. Each line represents the measurement of antibody levels in an individual at different ages.

Figure 6

(a) The decline and acquisition of antibody isotypes IgG1, IgG2, IgG3, IgG4, IgM and IgA to MSP2-ch150/9 at the ages 0, 4, 9, 18 and 36 months. Each line represents the measurement of antibody levels for an individual at different ages. (b) The decline and acquisition of the antibody isotypes, IgG1, IgG2, IgG3, IgG4, IgM and IgA, to MSP2-Dd2 over the five time points 0, 4, 9, 18 and 36 months. Each line represents the measurement of antibody levels in an individual at different ages.