Differential Recognition of P. falciparum VAR2CSA Domains by Naturally Acquired Antibodies in Pregnant Women from a Malaria Endemic Area

Background

Plasmodium falciparum infected red blood cells (iRBC)express variant surface antigens (VSA) of which VAR2CSA is involved inplacental sequestration and causes pregnancy-associated malaria (PAM).Primigravidae are most susceptible to PAM whereas antibodies associated withprotection are often present at higher levels in multigravid women. However,HIV co-infection with malaria has been shown to alter this parity-dependentacquisition of immunity, with more severe symptoms as well as more malariaepisodes in HIV positive women versus HIV negative women of a similarparity.

Methods

Using VAR2CSA DBL-domains expressed on the surface of CHO-745 cells wequantified levels of DBL-domain specific IgG in sera from pregnant Malawianwomen by flow cytometry. Dissociations constants of DBL5ε specificantibodies were determined using a surface plasmon resonance technique, asan indication of antibody affinities.

Results

VAR2CSA DBL5ε was recognized in a gender and parity-dependent mannerwith anti-DBL5ε IgG correlating significantly with IgG levels toVSA-PAM on the iRBC surface. HIV positive women had lower levels ofanti-DBL5ε IgG than HIV negative women of similar parity. Inprimigravidae, antibodies in HIV positive women also showed significantlylower affinity to VAR2CSA DBL5ε.

Conclusions

Pregnant women from a malaria-endemic area had increased levels ofanti-DBL5ε IgG by parity, indicating this domain of VAR2CSA to be apromising vaccine candidate against PAM. However, it is important toconsider co-infection with HIV, as this seems to change the properties ofantibody response against malaria. Understanding the characteristics ofantibody response against VAR2CSA is undoubtedly imperative in order todesign a functional and efficient vaccine against PAM.