title: Differential recognition of P. falciparum VAR2CSA domains by naturally acquired antibodies in pregnant women from a malaria endemic area.
abstract: BACKGROUND
  Plasmodium falciparum infected red blood cells (iRBC) express variant surface antigens (VSA) of which VAR2CSA is involved in placental sequestration and causes pregnancy-associated malaria (PAM). Primigravidae are most susceptible to PAM whereas antibodies associated with protection are often present at higher levels in multigravid women. However, HIV co-infection with malaria has been shown to alter this parity-dependent acquisition of immunity, with more severe symptoms as well as more malaria episodes in HIV positive women versus HIV negative women of a similar parity.
  
  
  METHODS
  Using VAR2CSA DBL-domains expressed on the surface of CHO-745 cells we quantified levels of DBL-domain specific IgG in sera from pregnant Malawian women by flow cytometry. Dissociations constants of DBL5epsilon specific antibodies were determined using a surface plasmon resonance technique, as an indication of antibody affinities.
  
  
  RESULTS
  VAR2CSA DBL5epsilon was recognized in a gender and parity-dependent manner with anti-DBL5epsilon IgG correlating significantly with IgG levels to VSA-PAM on the iRBC surface. HIV positive women had lower levels of anti-DBL5epsilon IgG than HIV negative women of similar parity. In primigravidae, antibodies in HIV positive women also showed significantly lower affinity to VAR2CSA DBL5epsilon.
  
  
  CONCLUSIONS
  Pregnant women from a malaria-endemic area had increased levels of anti-DBL5epsilon IgG by parity, indicating this domain of VAR2CSA to be a promising vaccine candidate against PAM. However, it is important to consider co-infection with HIV, as this seems to change the properties of antibody response against malaria. Understanding the characteristics of antibody response against VAR2CSA is undoubtedly imperative in order to design a functional and efficient vaccine against PAM.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Kim J M
authors.initials: KJ
authors.lastname: Brolin
authors.forename: Kristina E M
authors.initials: KE
authors.lastname: Persson
authors.forename: Mats
authors.initials: M
authors.lastname: Wahlgren
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rogerson
authors.forename: Qijun
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000328:Adult; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000915:Antibody Affinity / Q000276:immunology; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D016466:CHO Cells; D015897:Comorbidity; D006224:Cricetinae; D003412:Cricetulus; D019353:Endemic Diseases; D000939:Epitopes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D020073:Gravidity; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology; D008295:Malawi / Q000453:epidemiology; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000453:epidemiology / Q000276:immunology*; D020349:Surface Plasmon Resonance
chemical_list: D000906:Antibodies; D000953:Antigens, Protozoan; D000939:Epitopes; D007074:Immunoglobulin G; C512601:VAR2CSA protein, Plasmodium falciparum