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The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria

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ABSTRACT

Understanding the targets and mechanisms of human immunity to malaria is important for advancing the development of highly efficacious vaccines and serological tools for malaria surveillance. The PfRH5 and PfRipr proteins form a complex on the surface of P. falciparum merozoites that is essential for invasion of erythrocytes and are vaccine candidates. We determined IgG subclass responses to these proteins among malaria-exposed individuals in Papua New Guinea and their association with protection from malaria in a longitudinal cohort of children. Cytophilic subclasses, IgG1 and IgG3, were predominant with limited IgG2 and IgG4, and IgG subclass-specific responses were higher in older children and those with active infection. High IgG3 to PfRH5 and PfRipr were significantly and strongly associated with reduced risk of malaria after adjusting for potential confounding factors, whereas associations for IgG1 responses were generally weaker and not statistically significant. Results further indicated that malaria exposure leads to the co-acquisition of IgG1 and IgG3 to PfRH5 and PfRipr, as well as to other PfRH invasion ligands, PfRH2 and PfRH4. These findings suggest that IgG3 responses to PfRH5 and PfRipr may play a significant role in mediating naturally-acquired immunity and support their potential as vaccine candidates and their use as antibody biomarkers of immunity.

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Seroprevalence of total IgG and subclass response to PfRH5 and PfRipr by concurrent parasitemia measured by PCR.Results are shown as percentage seropositive, as determined by ELISA. Error bars indicate standard error of proportion (SE). Results are shown by parasitemic status at enrolment (PCR(−) or PCR(+)). Top row: PfRH5 Bottom row: PfRipr. Results are shown for (A)/(D) Total IgG, (B)/(E) IgG1 and (C)/(F) IgG3 left to right. P values indicate chi square test.
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f3: Seroprevalence of total IgG and subclass response to PfRH5 and PfRipr by concurrent parasitemia measured by PCR.Results are shown as percentage seropositive, as determined by ELISA. Error bars indicate standard error of proportion (SE). Results are shown by parasitemic status at enrolment (PCR(−) or PCR(+)). Top row: PfRH5 Bottom row: PfRipr. Results are shown for (A)/(D) Total IgG, (B)/(E) IgG1 and (C)/(F) IgG3 left to right. P values indicate chi square test.

Mentions: Previous studies have shown individuals with active P. falciparum infection generally have higher levels of antibodies to merozoite antigens4632. In our cohort, IgG3 and IgG1 responses to PfRH5 were significantly higher in PCR positive compared to PCR negative individuals. The prevalences of IgG3 responses were 43.3 and 64% for PCR(−) and PCR(+), respectively, (p = <0.001); prevelances of IgG1 responses were 25.4% and 36.0% (p = 0.002). PfRipr-specific IgG3 seroprevalence was higher in PCR positive compared to PCR negative individuals (PCR(−): 53.7%, PCR(+): 66.2%, p = 0.01), but the difference was less marked for IgG1 responses (PCR(−): 53.7%, PCR(+): 66.2%, p = 0.07) (Fig. 3).


The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria
Seroprevalence of total IgG and subclass response to PfRH5 and PfRipr by concurrent parasitemia measured by PCR.Results are shown as percentage seropositive, as determined by ELISA. Error bars indicate standard error of proportion (SE). Results are shown by parasitemic status at enrolment (PCR(−) or PCR(+)). Top row: PfRH5 Bottom row: PfRipr. Results are shown for (A)/(D) Total IgG, (B)/(E) IgG1 and (C)/(F) IgG3 left to right. P values indicate chi square test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5015043&req=5

f3: Seroprevalence of total IgG and subclass response to PfRH5 and PfRipr by concurrent parasitemia measured by PCR.Results are shown as percentage seropositive, as determined by ELISA. Error bars indicate standard error of proportion (SE). Results are shown by parasitemic status at enrolment (PCR(−) or PCR(+)). Top row: PfRH5 Bottom row: PfRipr. Results are shown for (A)/(D) Total IgG, (B)/(E) IgG1 and (C)/(F) IgG3 left to right. P values indicate chi square test.
Mentions: Previous studies have shown individuals with active P. falciparum infection generally have higher levels of antibodies to merozoite antigens4632. In our cohort, IgG3 and IgG1 responses to PfRH5 were significantly higher in PCR positive compared to PCR negative individuals. The prevalences of IgG3 responses were 43.3 and 64% for PCR(−) and PCR(+), respectively, (p = <0.001); prevelances of IgG1 responses were 25.4% and 36.0% (p = 0.002). PfRipr-specific IgG3 seroprevalence was higher in PCR positive compared to PCR negative individuals (PCR(−): 53.7%, PCR(+): 66.2%, p = 0.01), but the difference was less marked for IgG1 responses (PCR(−): 53.7%, PCR(+): 66.2%, p = 0.07) (Fig. 3).

View Article: PubMed Central - PubMed

ABSTRACT

Understanding the targets and mechanisms of human immunity to malaria is important for advancing the development of highly efficacious vaccines and serological tools for malaria surveillance. The PfRH5 and PfRipr proteins form a complex on the surface of P. falciparum merozoites that is essential for invasion of erythrocytes and are vaccine candidates. We determined IgG subclass responses to these proteins among malaria-exposed individuals in Papua New Guinea and their association with protection from malaria in a longitudinal cohort of children. Cytophilic subclasses, IgG1 and IgG3, were predominant with limited IgG2 and IgG4, and IgG subclass-specific responses were higher in older children and those with active infection. High IgG3 to PfRH5 and PfRipr were significantly and strongly associated with reduced risk of malaria after adjusting for potential confounding factors, whereas associations for IgG1 responses were generally weaker and not statistically significant. Results further indicated that malaria exposure leads to the co-acquisition of IgG1 and IgG3 to PfRH5 and PfRipr, as well as to other PfRH invasion ligands, PfRH2 and PfRH4. These findings suggest that IgG3 responses to PfRH5 and PfRipr may play a significant role in mediating naturally-acquired immunity and support their potential as vaccine candidates and their use as antibody biomarkers of immunity.

No MeSH data available.


Related in: MedlinePlus