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

• Published in: Frontiers in immunology Vol. 12; p. 634738
• Main Authors: Arévalo-Herrera, Myriam, Miura, Kazutoyo, Cespedes, Nora, Echeverry, Carlos, Solano, Eduardo, Castellanos, Angélica, Ramirez, Juan Sebastián, Miranda, Adolfo, Kajava, Andrey V., Long, Carole, Corradin, Giampietro, Herrera, Sócrates
• Format: Journal Article
• Language: English
• Published: Frontiers 24.06.2021; Frontiers Media S.A
• Subjects: gametocytes; Human health and pathology; Immunology; Infectious diseases; Life Sciences; malaria; Microbiology and Parasitology; Parasitology; Plasmodium vivax; Pvs48/45; transmission blocking; vaccines; Vaccinology; Plasmodium vivax; transmission blocking; Malaria; gametocytes; vaccines; Pvs48/45
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.634738

P48/45 is a conserved gametocyte antigen involved in Plasmodium parasite fertilization. A recombinant Plasmodium vivax P48/45 ( Pvs 48/45) 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 Pvs 48/45 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- rPvs 48/45 protein was 46.3%, while for E. coli - rPvs 48/45 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 rPvs 48/45 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-r Pvs 48/45 protein was more immunoreactive in most of the malaria endemic places studied, and CHO-r Pvs 48/45 specific IgG showed functional activity, supporting further testing of the protein vaccine potential.