author = {A. E. Barry, A. Trieu, F. J. I. Fowkes, J. Pablo, M. Kalantari-Dehaghi, A. Jasinskas, X. Tan, M.A. Kayala, L. Tavul, P.M. Siba, K. P. Day, P. Baldi, P. L. Felgner, D. L. Doolan},
   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.},
   journal = {Molecular and Cellular Proteomics},
   volume = {},
   number = {},
   pages = {},
   note = {},
   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 (PNG) to seroprofile 38 non-immune children (< 4 yrs) and 29 hyper-immune adults (≥15 yrs) from the same local area. The overall magnitude, prevalence and breadth of antibody response to VAR was limited at <2 yrs and 2-2.9 yrs, peaked at 3-4 yrs and decreased for adults compared to the oldest children. An increasing proportion of individuals recognised large numbers of VAR proteins (>20) with age, consistent with the breadth of response stabilising with age. In addition, the antibody response was limited in uninfected children compared to 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, (< 3yrs), from later in childhood (≥ 3yrs) or rarely recognised. Group 2 VAR proteins (Cys2/MFK-REY+) were serodominant in infants (<1 y.o.) 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.},
   keywords = {},
   year = {2011}