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

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.

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Risk of symptomatic P. falciparum episode during follow-up relative to IgG1 and IgG3 to PfRH5.Kaplan-Meier curves show the proportion of children that remained free of malaria episodes over time for IgG subclass responses against PfRH5 and PfRipr (A) IgG1 to PfRH5; (B) IgG3 to PfRH5; (C) IgG1 to PfRipr; (D) IgG3 to PfRH5. Antibody responses were divided into 3 equal response groups: high (green line), medium (red line), and low (blue line) antibody reactivity. Unadjusted data are shown. Wilcoxon log rank tests were carried out: (A) p = 0.004; (B) p < 0.001; (C) p < 0.001; (D) p < 0.001 Symptomatic P. falciparum infection was defined as fever (>37 °C) plus a parasite load of 5000 parasites/μl.
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f4: Risk of symptomatic P. falciparum episode during follow-up relative to IgG1 and IgG3 to PfRH5.Kaplan-Meier curves show the proportion of children that remained free of malaria episodes over time for IgG subclass responses against PfRH5 and PfRipr (A) IgG1 to PfRH5; (B) IgG3 to PfRH5; (C) IgG1 to PfRipr; (D) IgG3 to PfRH5. Antibody responses were divided into 3 equal response groups: high (green line), medium (red line), and low (blue line) antibody reactivity. Unadjusted data are shown. Wilcoxon log rank tests were carried out: (A) p = 0.004; (B) p < 0.001; (C) p < 0.001; (D) p < 0.001 Symptomatic P. falciparum infection was defined as fever (>37 °C) plus a parasite load of 5000 parasites/μl.

Mentions: To investigate the association between antibody responses and protection from symptomatic P. falciparum malaria, the children were divided into three equal tertiles representing high, medium and low antibody levels for each subclass response and survival analyses were performed. In Kaplan-Meier survival analyses (unadjusted), there were significant differences between the three IgG subclass groups, with high responders having a longer time to first symptomatic P. falciparum episode than medium and low responders for both PfRH5 and PfRipr (PfRH5 IgG1: p = 0.004, IgG3: p < 0.001; PfRipr IgG1, IgG3 both p < 0.001) (Fig. 4).


The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria
Risk of symptomatic P. falciparum episode during follow-up relative to IgG1 and IgG3 to PfRH5.Kaplan-Meier curves show the proportion of children that remained free of malaria episodes over time for IgG subclass responses against PfRH5 and PfRipr (A) IgG1 to PfRH5; (B) IgG3 to PfRH5; (C) IgG1 to PfRipr; (D) IgG3 to PfRH5. Antibody responses were divided into 3 equal response groups: high (green line), medium (red line), and low (blue line) antibody reactivity. Unadjusted data are shown. Wilcoxon log rank tests were carried out: (A) p = 0.004; (B) p < 0.001; (C) p < 0.001; (D) p < 0.001 Symptomatic P. falciparum infection was defined as fever (>37 °C) plus a parasite load of 5000 parasites/μl.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC5015043&req=5

f4: Risk of symptomatic P. falciparum episode during follow-up relative to IgG1 and IgG3 to PfRH5.Kaplan-Meier curves show the proportion of children that remained free of malaria episodes over time for IgG subclass responses against PfRH5 and PfRipr (A) IgG1 to PfRH5; (B) IgG3 to PfRH5; (C) IgG1 to PfRipr; (D) IgG3 to PfRH5. Antibody responses were divided into 3 equal response groups: high (green line), medium (red line), and low (blue line) antibody reactivity. Unadjusted data are shown. Wilcoxon log rank tests were carried out: (A) p = 0.004; (B) p < 0.001; (C) p < 0.001; (D) p < 0.001 Symptomatic P. falciparum infection was defined as fever (>37 °C) plus a parasite load of 5000 parasites/μl.
Mentions: To investigate the association between antibody responses and protection from symptomatic P. falciparum malaria, the children were divided into three equal tertiles representing high, medium and low antibody levels for each subclass response and survival analyses were performed. In Kaplan-Meier survival analyses (unadjusted), there were significant differences between the three IgG subclass groups, with high responders having a longer time to first symptomatic P. falciparum episode than medium and low responders for both PfRH5 and PfRipr (PfRH5 IgG1: p = 0.004, IgG3: p < 0.001; PfRipr IgG1, IgG3 both p < 0.001) (Fig. 4).

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