AUTHOR=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 

TITLE=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

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.634738

DOI=10.3389/fimmu.2021.634738

ISSN=1664-3224

ABSTRACT=<p>P48/45 is a conserved gametocyte antigen involved in <italic>Plasmodium</italic> parasite fertilization. A recombinant <italic>Plasmodium vivax</italic> P48/45 (<italic>Pvs</italic>48/45) protein expressed in <italic>Escherichia coli</italic> (<italic>E. coli</italic>) was highly antigenic and immunogenic in experimental animals and elicited specific transmission-blocking (TB) antibodies in a previous pilot study. Here, a similar <italic>Pvs</italic>48/45 gene was expressed in Chinese Hamster Ovary (CHO) cells and we compared its immunoreactivity with the <italic>E. coli</italic> product. Specific antibody titers were determined using plasma from Colombian individuals (n=227) living in endemic areas where both <italic>P. vivax</italic> and <italic>P. falciparum</italic> are prevalent and from Guatemala (n=54) where <italic>P. vivax</italic> is highly prevalent. In Colombia, plasma seroprevalence to CHO-<italic>rPvs</italic>48/45 protein was 46.3%, while for <italic>E. coli</italic>-<italic>rPvs</italic>48/45 protein was 36.1% (<italic>p&lt;</italic>0.001). In Guatemala, the sero prevalence was 24.1% and 14.8% (<italic>p&lt;</italic>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. <italic>Ex vivo P. vivax</italic> 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 <italic>rPvs</italic>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<italic>Pvs</italic>48/45 protein was more immunoreactive in most of the malaria endemic places studied, and CHO-r<italic>Pvs</italic>48/45 specific IgG showed functional activity, supporting further testing of the protein vaccine potential.</p>