Poster Presentation First Malaria World Congress 2018

Plasmodium vivax reticulocytes binding proteins (PvRBP) are immune targets in clinical isolates from Timika, Papua, Indonesia (#467)

Wen-Qiang He 1 2 , Indra Wibowo 3 , Sebastien Menant 1 2 , Leily Trianty 4 5 , Retno Utami 4 5 , Dwi Apriyanti 4 5 , Agatha Puspitasari 4 5 , Nadia Fadilah 4 5 , Benediktus Andries 6 , Enny Kenangalem 6 , Jeanne Rini Poespoprodjo 6 , Jutta Marfurt 7 , Ric Price 7 , Lisa Ioannidis 1 2 , Diana Hansen 1 2 , Alan Cowman 1 2 , Wai-Hong Tham 1 2 , Rintis Noviyanti 4 5
  1. Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
  2. Department of Medical Biology, University of Melbourne, Melbourne, Australia
  3. School of Life Sciences and Technology, Institut Teknologi Bandung, Bandung, Indonesia
  4. Eijkman Institute for Molecular Biology, Jakarta, Indonesia
  5. Ministry of Research, Technology, and Higher Education, Jakarta, Indonesia
  6. Papuan Health and Community Development Foundation, Timika, Papua, Indonesia
  7. Menzies School of Health Research, Darwin, Australia

Members of the Plasmodium vivax Reticulocyte Binding Protein (PvRBP) family are important parasite adhesins that function during parasite invasion. In a recent study, PvRBP2b was identified to bind Transferrin Receptor 1 to mediate a critical invasion pathway into reticulocytes. Using samples from Timika, Papua, we investigated the antibody responses to PvRBP2b and five other PvRBPs, and their relationship with age, concurrent infection and clinical malaria. In addition, we wanted to determine if the plasma contained antibodies with functional blocking activity against PvRBP2b. One hundred and nineteen samples were collected from two villages and hospital in Timika with a broad age range of 5 to 41 years old spanning a period between July-December 2014 and September-December 2017.  The total IgG levels against PvRBP2a and PvRBP2b from symptomatic individuals were significantly higher than those without any infection (P≤0.033), suggesting that these two antigens could be potential markers of current symptomatic infection. The level of PvRBP2a and PvRBP2b antibodies were positively correlated with parasitemia (Rho=0.190-0.242, P≤ 0.038), haemoglobin level (Rho=0.238-0.258, P≤0.01), and enlarged spleens (OR=2.43-3.29, P ≤ 0.006 for PvRBP2a and PvRBP2b, and OR=1.87, P=0.049 for PvRBP1a). Due to small numbers of reinfections, we were unable to determine whether higher antibody levels to PvRBP2a and PvRBP2b were correlated with reduced risk of reinfection. We performed reticulocyte binding assays with recombinant PvRBP2b and observed that 12 samples contained functional blocking antibodies. In addition, we observed that high responders to PvRBP2b from symptomatic individuals showed a higher level of binding inhibition compared to asymptomatic and healthy control individuals (P=0.017). This study demonstrates that PvRBP2a and PvRBP2b as targets of naturally acquired immunity to P. vivax and suggests that a deeper understanding on the mechanism of blocking antibodies will provide insights on strategies to prevent P. vivax invasion.