Immunoreactivity of Sera From Low to Moderate Malaria-Endemic Areas Against Plasmodium vivax rPvs48/45 Proteins Produced in Escherichia coli and Chinese Hamster Ovary Systems

• DOI: 10.3389/fimmu.2021.634738
• Publication Date: 2021-06-24T05:24:07Z
• Authors: Myriam Arévalo-He...; Kazutoyo Miura; Nora Cespedes; Carlos Echeverry; Eduardo Solano; Angélica Castellanos; Juan Sebastián Ra...; Adolfo Miranda; Andrey V. Kajava; Carole Long; Giampietro Corradin; Sócrates Herrera
• Keywords: Adult; Male; Adolescent; Endemic Diseases; gametocytes; Immunology; malaria; Antibodies, Protozoan; Antigens, Protozoan; CHO Cells; Colombia; 03 medical and health sciences; [SDV.IMM.VAC] Life Sciences [q-bio]/Immunology/Vaccinology; Cricetulus; 0302 clinical medicine; [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases; Antibody Specificity; Escherichia coli; Malaria, Vivax; Animals; Humans; [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology; Child; Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antibodies, Protozoan/blood; Antibody Specificity; Antigens, Protozoan/genetics; Antigens, Protozoan/immunology; Antigens, Protozoan/metabolism; CHO Cells; Child; Colombia/epidemiology; Cricetulus; Endemic Diseases; Escherichia coli/genetics; Escherichia coli/metabolism; Female; Guatemala/epidemiology; Humans; Immunoglobulin G/blood; Malaria, Vivax/blood; Malaria, Vivax/diagnosis; Malaria, Vivax/epidemiology; Malaria, Vivax/immunology; Male; Middle Aged; Plasmodium vivax/immunology; Plasmodium vivax/pathogenicity; Predictive Value of Tests; Recombinant Proteins/immunology; Recombinant Proteins/metabolism; Seroepidemiologic Studies; Serologic Tests; Young Adult; Plasmodium vivax; Pvs48/45; gametocytes; malaria; transmission blocking; vaccines; Aged; Aged, 80 and over; Pvs48/45; RC581-607; vaccines; Guatemala; Malaria; 3. Good health; Immunoglobulin G; [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases; transmission blocking; Female; [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology; Immunologic diseases. Allergy; Plasmodium vivax; [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology

P48/45 is a conserved gametocyte antigen involved in Plasmodium parasite fertilization. A recombinant Plasmodium vivax P48/45 (Pvs48/45) protein expressed in Escherichia coli (E. coli) was highly antigenic and immunogenic in experimental animals and elicited specific transmission-blocking (TB) antibodies in a previous pilot study. Here, a similar Pvs48/45 gene was expressed in Chinese Hamster Ovary (CHO) cells and we compared its immunoreactivity with the E. coli product. Specific antibody titers were determined using plasma from Colombian individuals (n=227) living in endemic areas where both P. vivax and P. falciparum are prevalent and from Guatemala (n=54) where P. vivax is highly prevalent. In Colombia, plasma seroprevalence to CHO-rPvs48/45 protein was 46.3%, while for E. coli-rPvs48/45 protein was 36.1% (p<0.001). In Guatemala, the sero prevalence was 24.1% and 14.8% (p<0.001), respectively. Reactivity index (RI) against both proteins showed an age-dependent increase. IgG2 was the predominant subclass and the antibody avidity index evaluated by ELISA ranged between 4-6 mol/L. Ex vivo P. vivax mosquito direct membrane feeding assays (DMFA) performed in presence of study plasmas, displayed significant parasite transmission-blocking (TB), however, there was no direct correlation between antibody titers and oocysts transmission reduction activity (%TRA). Nevertheless, DMFA with CHO rPvs48/45 affinity purified IgG showed a dose response; 90.2% TRA at 100 μg/mL and 71.8% inhibition at 10 μg/mL. In conclusion, the CHO-rPvs48/45 protein was more immunoreactive in most of the malaria endemic places studied, and CHO-rPvs48/45 specific IgG showed functional activity, supporting further testing of the protein vaccine potential.