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.

Keywords: Antibody responses; Cross reactivity; Plasmodium falciparum; Plasmodium vivax.

Figure 1. ELISA results for Pfs48/45 and Pvs48/45

Absorbance (405 nm) with Bemberi 2013 (A) and Bemberi 2015 (B) plasma samples reacting with recombinant Pfs48/45 and Pvs48/45 antigens.

Figure 1. ELISA results for Pfs48/45 and Pvs48/45

Absorbance (405 nm) with Bemberi 2013 (A) and Bemberi 2015 (B) plasma samples reacting with recombinant Pfs48/45 and Pvs48/45 antigens.

Figure 2. Western blot Analysis

Images of representative plasma samples (1:200 dilutions) reacting with Pfs48/45 (A) and Pvs48/45 (B).

Figure 3. Results of nested PCR for P. falciparum (A) and P. vivax (B)

Lane marked L shows a 50 base pair molecular mass marker ladder and the number on top show the samples IDs of Bemberi 2013 participants. Lane marked Pf contained P. falciparum (NF54) genomic DNA and lane marked Pv contained P. vivax (Sal1 strain) genomic DNA.