IgG3 antibodies to Plasmodium falciparum merozoite surface protein 2 (MSP2): increasing prevalence with age and association with clinical immunity to malaria.

Abstract

In a cross-sectional survey carried out in west Africa (The Gambia), where Plasmodium falciparum malaria is endemic with seasonal transmission, 178 individuals 1-75 years of age were assessed for their antibody response to the malaria vaccine candidate, merozoite surface protein 2 (MSP2). Total IgG to recombinant antigens representing full-length, repetitive, and group-specific domains of both allelic families of MSP2 was determined by ELISA. The IgG-subclass profile of IgG-positive sera was assessed. Antibody prevalence was age-dependent, reaching a peak during adolescence. In MSP2-seropositive individuals, there was a predominance of cytophilic antibodies (IgG1 and IgG3); IgG1 antibodies were prevalent in children less than 10 years of age, whereas in adolescents and adults MSP2-specific antibodies were predominantly IgG3. In parallel, we conducted a longitudinal study of children (3-8 years of age) from the same community; sera collected before the malaria transmission season were tested for the presence of anti-MSP2 antibodies. The subsequent susceptibility of these children to clinical malaria was monitored and the association between anti-MSP2 antibodies of different IgG subclasses and resistance to clinical malaria was tested. The presence of IgG3 antibodies to MSP2 serogroup A was negatively associated with the risk of clinical malaria whereas IgG1 antibodies to MSP2 serogroup B were associated with an increased risk of clinical infection. Our data suggest that age/exposure-related acquisition of IgG3 antibodies to MSP2 may contribute to the development of clinically protective immunity to malaria.

The London School of Hygiene and Tropical Medicine: a new century of malaria research

“…Population genetic approaches can help to identify potential protective antigens (see above) but more direct approaches, such as immunoepidemiological studies of the association between a specific immune response to a particular antigen and susceptibility or resistance to clinical malaria, can also be used (Riley et al 1991, Al-Yaman et al 1994, Taylor et al 1998). We have recently completed an immunoepidemiological study designed to test whether anti-malarial antibodies transferred from mother to child across the placenta, can in fact protect neonates and infants from malaria infection or malaria disease.…”

Polymorphism at the merozoite surface protein-3alpha locus of Plasmodium vivax: global and local diversity.

“…The analysis is based on the evaluation of the presence and number of P. vivax merozoite surface protein-3␣ (PvMsp-3␣) alleles. 7 Proteins on the surface of Plasmodium merozoites are targets of naturally acquired [8][9][10] and vaccine-induced immunity against malaria. 11,12 The PvMsp-3␣ 7 is a member of an Msp3 gene family that is genetically related to P. falciparum merozoite surface protein-3 (PfMsp-3).…”

Igg Subclasses Targeting the Flagella of Salmonella Enterica Serovar Typhimurium Can Mediate Phagocytosis and Bacterial Killing

“…The greater flexibility of the hinge region of IgG3 probably allows IgG3 to associate better with activating Fcγ receptors such as FcγRI and FcγRIIA [46,48,49] to mediate efficient bacterial uptake and the subsequent intracellular bacterial killing, possibly hence resulting in lower host cell death at 8 h p.i.. In fact, Th1-associated IgG3 has been shown to be more advantageous than the other subclasses in other infection systems, where IgG3 is negatively associated with progression of clinical diseases [50]. We have recently demonstrated that Th1-associated murine IgG2a and IgG2b were the most efficient isotypes at lowering Salmonella bacterial load in the blood, liver and spleen in vivo following infection in mouse [51].…”