title: The stability and complexity of antibody responses to the major surface antigen of Plasmodium falciparum are associated with age in a malaria endemic area.
abstract: Individuals that are exposed to malaria eventually develop immunity to the disease with one possible mechanism being the gradual acquisition of antibodies to the range of parasite variant surface antigens in their local area. Major antibody targets include the large and highly polymorphic Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) family of proteins. Here, we use a protein microarray containing 123 recombinant PfEMP1-DBLα domains (VAR) from Papua New Guinea to seroprofile 38 nonimmune children (<4 years) and 29 hyperimmune adults (≥15 years) from the same local area. The overall magnitude, prevalence and breadth of antibody response to VAR was limited at <2 years and 2-2.9 years, peaked at 3-4 years and decreased for adults compared with the oldest children. An increasing proportion of individuals recognized large numbers of VAR proteins (>20) with age, consistent with the breadth of response stabilizing with age. In addition, the antibody response was limited in uninfected children compared with infected children but was similar in adults irrespective of infection status. Analysis of the variant-specific response confirmed that the antibody signature expands with age and infection. This also revealed that the antibody signatures of the youngest children overlapped substantially, suggesting that they are exposed to the same subset of PfEMP1 variants. VAR proteins were either seroprevalent from early in life, (<3 years), from later in childhood (≥3 years) or rarely recognized. Group 2 VAR proteins (Cys2/MFK-REY+) were serodominant in infants (<1-year-old) and all other sequence subgroups became more seroprevalent with age. The results confirm that the anti-PfEMP1-DBLα antibody responses increase in magnitude and prevalence with age and further demonstrate that they increase in stability and complexity. The protein microarray approach provides a unique platform to rapidly profile variant-specific antibodies to malaria and suggests novel insights into the acquisition of immunity to malaria.
authors.affiliation: Centre for Population Health, Burnet Institute, Melbourne, Victoria 3004, Australia. barry@wehi.edu.au
authors.forename: Alyssa E
authors.initials: AE
authors.lastname: Barry
authors.forename: Angela
authors.initials: A
authors.lastname: Trieu
authors.forename: Freya J I
authors.initials: FJ
authors.lastname: Fowkes
authors.forename: Jozelyn
authors.initials: J
authors.lastname: Pablo
authors.forename: Mina
authors.initials: M
authors.lastname: Kalantari-Dehaghi
authors.forename: Algis
authors.initials: A
authors.lastname: Jasinskas
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Tan
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Kayala
authors.forename: Livingstone
authors.initials: L
authors.lastname: Tavul
authors.forename: Peter M
authors.initials: PM
authors.lastname: Siba
authors.forename: Karen P
authors.initials: KP
authors.lastname: Day
authors.forename: Pierre
authors.initials: P
authors.lastname: Baldi
authors.forename: Philip L
authors.initials: PL
authors.lastname: Felgner
authors.forename: Denise L
authors.initials: DL
authors.lastname: Doolan
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000917:Antibody Formation; D000953:Antigens, Protozoan / Q000276:immunology* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D019353:Endemic Diseases; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000276:immunology* / Q000469:parasitology; D010219:Papua New Guinea / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000276:immunology* / Q000378:metabolism; D040081:Protein Array Analysis; D020033:Protein Isoforms; D015800:Protozoan Proteins / Q000276:immunology* / Q000378:metabolism; D016036:Seroepidemiologic Studies; D055815:Young Adult
chemical_list: D000953:Antigens, Protozoan; D020033:Protein Isoforms; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum