Background
Primigravid (PG) women are at risk for pregnancy-associated malaria (PAM). Multigravid (MG) women acquire
protection against PAM; however, HIV infection impairs this protective response. Protection against PAM is associated with the production of IgG
specific for variant surface antigens (VSA-PAM) expressed by chondroitin sulfate A (CSA)-adhering parasitized erythrocytes (PEs). We hypothesized that VSA-PAM-specific IgG confers protection by promoting opsonic
phagocytosis of PAM isolates and that HIV infection impairs this response.
Methods and Findings
We assessed the ability of VSA-PAM-specific IgG to promote opsonic phagocytosis of CSA-adhering PEs and the impact of HIV infection on this process. Opsonic phagocytosis assays were performed using the CSA-adherent parasite line CS2 and human and murine macrophages. CS2 PEs were opsonized with plasma or purified IgG subclasses from HIV-negative or HIV-infected PG and MG Kenyan women or sympatric men. Levels of IgG subclasses specific for VSA-PAM were compared in HIV-negative and HIV-infected women by flow cytometry. Plasma from HIV-negative MG women, but not PG women or men, promoted the opsonic phagocytosis of CSA-binding PEs (p < 0.001). This function depended on VSA-PAM-specific plasma IgG1 and IgG3. HIV-infected MG women had significantly lower plasma opsonizing activity (median phagocytic index 46 interquartile range (IQR) 18195 versus 251 IQR 93397, p 0.006) and levels of VSA-PAM-specific IgG1 (mean fluorescence intensity MFI 13 IQR 1120 versus 30 IQR 2341, p < 0.001) and IgG3 (MFI 17 IQR 1423 versus 28 IQR 2337, p < 0.001) than their HIV-negative MG counterparts.
Conclusions
Opsonic phagocytosis may represent a novel correlate of protection against PAM. HIV infection may increase the susceptibility of multigravid women to PAM by impairing this clearance mechanism.