Plasmodium falciparum infections during pregnancy lead to sequestration of parasites in the placenta, increasing the risk of poor pregnancy outcomes. Sequestration can also result in the transfer of malaria antigens to the fetus that induces T cell priming, but little is known about the fetal B cell response to malaria.
To determine if antibodies were associated with low placental parasitemias and successful pregnancy outcomes, sera collected from 408 Cameroonian women at delivery, were screened for antibodies to nine vaccine-candidate antigens. Antibody responses to all but one antigen were higher in women who had placental malaria compared to uninfected women. These results suggest that antibodies had been produced in response to infection. However, antibodies to VAR2CSA were significantly higher in women with successful, normal pregnancies. Furthermore, antibodies to VAR2CSA were associated with inhibition of binding of parasitized erythrocytes to CSA and the reduction of placental parasitemias. Thus, antibodies to VAR2CSA reduce sequestration and provide some protective advantage to pregnant women and their newborns.
To assess in utero priming, cord blood mononuclear cells (CBMNC) were co-cultured with malaria antigens and mitogen for T cell proliferation, cytokine and antibody production. Results showed that CBMNC from 54% of newborns were able to proliferate in response to parasites extract stimulation, showing that antigen-specific memory T cells had been produced in utero. CBMNC from 92% and 53% of newborns secreted Th2- and Th1-type cytokines and 80% had cells secreting inflammatory cytokines. Thus, many newborns were exposed to malaria antigens in utero. Fetal B cells also responded to malaria antigens. CBMNC were cultured in vitro and supernatants were screened for antibodies to four vaccine-candidate antigens by ELISA and IFA. Results showed that 78% of newborns had B cells that secreted IgG antibodies to one or more antigens. The predominant isotypes were IgG1 and IgG3, the same isotype found in adults. This is the fits study to demonstrate that fetal B cells can isotype-switch in response to malaria. Since neonates in endemic areas are born with primed T and B cells, the effect of in utero priming on the acquisition of immunity in neonates merits further investigation.
|Advisor:||Taylor, Diane Wallace|
|School Location:||United States -- District of Columbia|
|Source:||DAI-B 69/12, Dissertation Abstracts International|
|Keywords:||Antibodies, Antigens, Cytokines, Immune response, Lymhocytes, Newborns, Plasmodium falciparum, Pregnant|
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