Naturally occurring antibodies to an epitope on Plasmodium falciparum gametes detected by monoclonal antibody-based competitive enzyme-linked immunosorbent assay

Abstract

The antibody response to an epitope on gamete antigens of Plasmodium fakciparum in persons naturally exposed to malaria has been investigated by competitive enzyme-linked immunosorbent assay. The assay detects antibodies to an epitope on the 48/45-kilodalton (kDa) gamete surface antigen by competition with horseradish peroxidase-labeled monoclonal antibody 11C5-B10. Five sera previously shown to immunoprecipitate the 230and 48/45-kDa antigens significantly inhibited 1IC5-B10 binding to an average of 24.2% of control. The one serum which precipitated only the 48/45-kDa antigen did not inhibit IIC5-B10 binding. For 26 sera which were negative by immunoprecipitation, mean binding in the assay was 112.7% of control (pooled London nonimmune sera). Recognition of both 230-kDa and 48/45-kDa antigens was associated with a titer of 1:9 or greater (reciprocal geometric mean titer, 27.6) for inhibition to more than 2 standard deviations from the mean of the negative sera. The results show that the 1IC5-B10 binding site is a naturally immunogenic epitope recognized by the majority of persons who had antibodies to the 48/45-kDa protein. An additional finding was enhancement of binding of 1IC5-B10 to an average of 154.4% of control by five sera which recognized only the 230-kDa antigen, presumably due to conformational alteration of the gamete antigen complex.

Association between anti‐Pfs48/45 reactivity and P. falciparum transmission‐blocking activity in sera from Cameroon

“…No reaction was found in our two-site ELISAs with MoAb 3G12. Enhancement of binding of HRPO-labelled MoAbs in the presence of sera to the captured antigen was never seen in these competition ELISAs (data not shown) in contrast to findings by Targett et al (1990b) or Graves et al (1988bGraves et al ( , 1991Graves et al ( and 1992.…”

“…In another study, MoAb IIC5.B10 was used to compete with a panel of Papua New Guinea sera. The results of the competition ELISA did not correlate with transmission-blocking activity observed in these field sera (Graves et al 1988a and1988b). We have previously described a correlation between suppression of infectivity of in vitro cultured gametocytes to mosquitoes in a bioassay and reactivity in an anti-Pfs48/45 two-site competition ELISA by immune sera (Roeffen et al 1995a).…”

“…A similar competition ELISA was used by Graves et al (1988bGraves et al ( , 1990Graves et al ( and 1992 and Ong et al (1990) with MoAbs including 3G12 against three different epitopes and X10 or XP12 as source of Pfs48/45. Graves et al (1992) showed a significant association between lack of infectivity of P. falciparum gametocyte carriers and recognition of epitope IIa on Pfs-48/45 by antibodies in their sera.…”

HIV-1 Impact on Malaria Transmission: A Complex and Relevant Global Health Concern

“…Foundational and novel studies have identified various factors that correlate with an increase in gametocytogenesis. These include, but are not limited to, host immunity Graves et al, 1988;Motard et al, 1995;Buckling et al, 1999), regulation of the key parasite genes GDV1 and AP2-G (Day et al, 1993;Eksi et al, 2012;Brancucci et al, 2014;Coleman et al, 2014;Kafsack et al, 2014;Filarsky et al, 2018;Josling et al, 2020), host lipid and biomolecule biosynthesis and metabolism (Gulati et al, 2015;Brancucci et al, 2017;Tanaka et al, 2019;Tewari et al, 2020), fluctuations in host hormone production (Trager and Gill, 1992;Lingnau et al, 1993), and chemotherapy (Puta and Manyando, 1997;Robert et al, 2000;Tjitra et al, 2002;Hamel et al, 2005;Elbasit et al, 2006;Schneider et al, 2006). Each of these triggers may be altered in the context of a co-morbidity such as HIV-1.…”

“…In the middle is a representation of the life cycle of Plasmodium falciparum (adapted from NIAID/NIH, 2016, https://www.niaid.nih.gov/diseases-conditions/malaria-parasite) representing the exoerythrocytic (liver) cycle, erythrocytic cycle (bloodstream), and sexual stage (gametocyte) development in the host, and the sporogonic cycle in the mosquito. Patnaik et al, 2005;9 Abu-Raddad et al, 2006;10 Laufer et al, 2006;11 Onyenekwe et al, 2007;12 Van Geertruyden et al, 2008;13 Stiffler et al, 2020;14 Trott et al, 2011;15 Koehler et al, 2009;16 Okonkwo et al, 2016;17 Mbale et al, 2016;18 Graves et al, 1988;19 Nassir et al, 2005;20 Lingnau et al, 1993;21 Bousema et al, 2011;22 Belperio and Rhew, 2004;23 Eksi et al, 2012;24 Brancucci et al, 2014;25 Josling et al, 2020;26 Coleman et al, 2014;27 Kafsack et al, 2014;28 Filarsky et al, 2018;29 Hobbs et al, 2013;30 Azevedo et al, 2019;31 Buckling et al, 1999;32 Elbasit et al, 2006;33 Ittiravivongs et al, 1984;34 Josling et al, 2018;35 Sandison et al, 2011;36 Puta and Manyando, 1997;37 Schneider et al, 2006;38 Barnes et al, 2008;39 Bouyou Akotet et al, 2018;40 Sowunmi et al, 2008;41 Quintero et al, 2011;42 Nacher et al, 2002;43 Tay et al, 2015;44 Sanyaolu et al, 2013;45 Hogh et al, 1998;…”