Seasonal fluctuation of antibody levels to Plasmodium falciparum parasitized red blood cell-associated antigens in two Senegalese villages with different transmission conditions.

Background Plasmodium falciparum merozoite surface protein 5 (PfMSP5) is an attractive blood stage vaccine candidate because it is both exposed to the immune system and well conserved. To evaluate its interest, we investigated the association of anti-PfMSP5 IgG levels, in the context of responses to two other conserved Ags PfMSP1p19 and R23, with protection from clinical episodes of malaria in cross-sectional prospective studies in two different transmission settings.MethodsNdiop (mesoendemic) and Dielmo (holoendemic) are two Senegalese villages participating in an on-going long-term observational study of natural immunity to malaria. Blood samples were taken before the transmission season (Ndiop) or before peak transmission (Dielmo) and active clinical surveillance was carried out during the ensuing 5.5-month follow-up. IgG responses to recombinant PfMSP5, PfMSP1p19 and R23 were quantified by ELISA in samples from surveys carried out in Dielmo (186 subjects) and Ndiop (221 subjects) in 2002, and Ndiop in 2000 (204 subjects). In addition, 236 sera from the Dielmo and Ndiop-2002 surveys were analyzed for relationships between the magnitude of anti-PfMSP5 response and neutrophil antibody dependent respiratory burst (ADRB) activity.ResultsAnti-PfMSP5 antibodies predominantly IgG1 were detected in 60–74% of villagers, with generally higher levels in older age groups. PfMSP5 IgG responses were relatively stable for Ndiop subjects sampled both in 2000 and 2002. ADRB activity correlated with age and anti-PfMSP5 IgG levels. Importantly, PfMSP5 antibody levels were significantly associated with reduced incidence of clinical malaria in all three cohorts. Inclusion of IgG to PfMSP1p19 in the poisson regression model did not substantially modify results.ConclusionThese results indicate that MSP5 is recognized by naturally acquired Ab. The large seroprevalence and association with protection against clinical malaria in two settings with differing transmission conditions and stability over time demonstrated in Ndiop argue for further evaluation of baculovirus PfMSP5 as a vaccine candidate.

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“…The Ags and ELISA test for IgG responses to PfMSP1p19 and to R23 was carried out as already described [13], [14], [22], [36], [37].…”

Section: Methodsmentioning

confidence: 99%

Association of Antibody Responses to the Conserved Plasmodium falciparum Merozoite Surface Protein 5 with Protection against Clinical Malaria

et al. 2014

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“…It is likely that there is a sustained and rapid renewal of specific IgG1 and IgG3, even in Ndiop, where transmission is seasonal, but probably not absent during the so-called dry season, because many adults have specific IgM. 7,11,12 These data, along with results obtained for this and other protective P. falciparum Ags, 12 argue that the production of specific IgG1 and IgG3 is adaptive. It would be of interest to investigate further the respective roles of long-lived IgG1 versus short-lived IgG3, not only in the acquisition but also in the maintenance of immunity to P. falciparum blood stage in populations exposed to this parasite.…”

Section: Igg3mentioning

confidence: 97%

Short report: differential evolution of immunoglobulin G1/G3 antibody responses to Plasmodium falciparum MSP1(19) over time in malaria-immune adult Senegalese patients.

Diallo

Spiegel²,

Diouf³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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Abstract. This study examined the evolution of immunoglobulin (Ig) G1 and IgG3 antibodies against the asexual stage Plasmodium falciparum protein, MSP1 19 , before and after a heavy malaria transmission period in clinically immune Senegalese subjects living under different epidemiological conditions. Plasma was tested for antibodies to a yeast-produced, recombinant PfMSP1 19 antigen (the Q-KNG allelic variant) that has previously been demonstrated to react with IgG1, IgG3, or both in the majority of these people. Anti-P. falciparum antibodies of the IgG1 and IgG3 subclasses, previously reported to be associated with protection, were shown to evolve independently one from another after the transmission period in both settings. These results suggest differential regulation of MSP1 19 -specific IgG1 and IgG3. The precise role of these antibody isotypes in maintaining malaria immunity remains to be determined.

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“…These Ags include polymorphic Ags located on the merozoite surface, such as MSP1 block 2 and MSP2, as well as conserved Ags associated with the red blood cell membrane, namely, Ag 332 (PfEB200) and Ag R45 (R23). The plasma Ab responses to these Ags in human populations exposed to P. falciparum infection have been documented in several seroepidemiological studies (10,11,(32)(33)(34)(35)41). Some Ags have conferred substantial protection in vaccination trials of nonhuman primates (36).…”

mentioning

confidence: 99%

Regulation of Antigen-Specific Immunoglobulin G Subclasses in Response to Conserved and PolymorphicPlasmodium falciparumAntigens in an In Vitro Model

Garraud¹,

Perraut²,

Diouf³

et al. 2002

Infect Immun

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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 [MSP1 19 ], 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 (MSP1 19 , 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.1 Passive transfer of hyperimmune immunoglobulin G (IgG) to malaria patients has shown that antibodies (Abs) play a key role in protection against Plasmodium falciparum blood stages (12,25,30). In vitro studies have indicated that efficient parasite destruction is achieved through interaction of Abs with monocytes. Binding of Abs to an infected red blood cell results in opsonization of the infected cell (24), and Ab-dependent cellular inhibition of parasite growth is triggered by the binding of an IgG-merozoite complex to monocytes (5, 6, 40). Both mechanisms have been reported to involve IgG1 and IgG3 but not IgG2, which is normally noncytophilic (4, 8, 23). The efficiency of Ab-dependent cellular inhibition of parasite growth depends on the relative proportion of parasite-specific IgG1 and IgG3 compared to IgG2 (4). The data indicate that the subclass distribution of IgG Abs reacting with merozoite surface antigens (Ags) is an important parameter for protection against P. falciparum blood stages. In order to develop efficient blood stage vaccines, we need to better understand anti-P. falciparum IgG subclass production and/or switching.Identification of the parasite and host factors affecting Ab production by B cells might indicate ways in which vaccineinduced immune responses can be directed to ensure terminal differe...

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Seasonal fluctuation of antibody levels to Plasmodium falciparum parasitized red blood cell-associated antigens in two Senegalese villages with different transmission conditions.

Cited by 18 publications

References 29 publications

Association of Antibody Responses to the Conserved Plasmodium falciparum Merozoite Surface Protein 5 with Protection against Clinical Malaria

Association of Antibody Responses to the Conserved Plasmodium falciparum Merozoite Surface Protein 5 with Protection against Clinical Malaria

Short report: differential evolution of immunoglobulin G1/G3 antibody responses to Plasmodium falciparum MSP1(19) over time in malaria-immune adult Senegalese patients.

Regulation of Antigen-Specific Immunoglobulin G Subclasses in Response to Conserved and PolymorphicPlasmodium falciparumAntigens in an In Vitro Model

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