Antibodies elicited during natural infection in a predominantly Plasmodium falciparum transmission area cross-react with sexual stage-specific antigen in P. vivax

Abstract

Infections caused by Plasmodium falciparum and P. vivax account for more than 90% of global malaria burden. Exposure to malaria parasite elicits immune responses during natural infection and it is generally believed that the immunity is not only stage specific but also species specific. However, partial genomic similarity for various antigens in different Plasmodium spp. raises the possibility of immunological cross-reactivity at the level of specific antigens. Serum samples collected from children who were permanent residents of a P. falciparum transmission area in Zimbabwe were screened for antibody reactivity against Pfs48/45, a P. falciparum gametocyte antigen and Pvs48/45, a P. vivax homolog of Pfs48/45 using ELISA. Western blotting was used to further confirm identity of the specific antibody reactivity to the Pfs48/45 and Pvs48/45 proteins. Pan Plasmodium PCR and nested PCR were used to confirm infection with the Plasmodium species. Twenty-seven percent (49/181) of the participants were found to be sero-positive for Pfs48/45 and 73% (n=36) of these Pfs48/45 positive sera also showed reactivity with Pvs48/45. Immune cross-reactivity revealed by ELISA was also confirmed by Western blot analysis using a panel of randomly selected 23 Pfs48/45 and Pvs48/45 ELISA positive samples. Nested PCR analysis of 27 blood samples randomly selected from the 36 that showed positive ELISA reactivity to both Pfs48/45 and Pvs48/45 antigens confirmed infection with P. falciparum and generalized absence of P. vivax except for a single sample which revealed PCR positivity for both P. vivax and P. falciparum. Our studies with sera samples from a predominantly P. falciparum transmission area in Zimbabwe suggest immunological cross-reactivity with Pvs48/45, thus raising the possibility of partial species cross-reactive immunity and possible cross-boosting of immunity during co-infection with P. falciparum and P. vivax.

Mosquito Bite-Induced Controlled Human Malaria Infection with Plasmodium vivax or P. falciparum Generates Immune Responses to Homologous and Heterologous Preerythrocytic and Erythrocytic Antigens

“…However, the presence of submicroscopic infections or the presence of residual antibodies from a previous infection(s) could not be ruled out by those authors. Similarly, there is a strong indication of the presence of cross-reactive responses to other sexual (17) and asexual (3,16,18) blood-stage antigens from the field. However, the data cannot be exclusively attributed to cross-reaction, as the presence of heterologous species, while rare, has not been ruled out.…”

“…Despite the presence of orthologous antigens, few studies have evaluated the presence of cross-reactive antibodies. Sera from regions with a predominance of one species, but not a total absence of the other species, have been shown to have cross-reactivity to some antigens, such as merozoite surface protein 1 (MSP-1) (15), MSP-5 (16), P. falciparum s48/45 (Pfs48/45) or P. vivax s48/45 (Pvs48/45) (17), and PfCLAG9 (18). Using P. falciparum and P. vivax protein microarrays, King and colleagues (3) observed cross-reactivity using sera from "essentially monoexposed" regions of endemicity.…”

Association of TNF (rs1800629) promoter polymorphism and schistosomiasis with sub‐microscopic asymptomatic Plasmodium falciparum infections in a schistosomiasis‐endemic area in Zimbabwe

“…Genomic DNA for the molecular diagnosis of asymptomatic P. falciparum and genotyping was extracted from whole blood using the Qiagen FlexiGene DNA Kit following the manufacturer’s protocol. A nested PCR protocol was used for molecular diagnosis of sub‐microscopic asymptomatic P. falciparum infections [30, 31].…”

The Case for Exploiting Cross-Species Epitopes in Malaria Vaccine Design

“…To the best of our knowledge, only the gametocyte antigen P48/45 has emerged as a candidate for cross-species recognition. Sera from school-aged children living in a P. falciparum endemic area of Zimbabwe were highly cross-reactive to the P. vivax homolog Pvs48/45 (76). Thirtysix of 49 (73%) samples positive for Pfs48/45 by ELISA also recognized Pvs48/45.…”