Cross-reactivity of r Pvs 48/45, a recombinant Plasmodium vivax protein, with sera from Plasmodium falciparum endemic areas of Africa
Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background
Ps 48/45, a Plasmodium gametocyte surface protein, is a promising candidate for malaria transmission-blocking (TB) vaccine. Due to its relevance for a multispecies vaccine, we explored the cross-reactivity and TB activity of a recombinant P. vivax Ps 48/45 protein (r Pvs 48/45) with sera from P. falciparum -exposed African donors.
Methods
r Pvs 48/45 was produced in Chinese hamster ovary cell lines and tested by ELISA for its cross-reactivity with sera from Burkina Faso, Tanzania, Mali, and Nigeria – In addition, BALB/c mice were immunized with the r Pvs 48/45 protein formulated in Montanide ISA-51 and inoculated with a crude extract of P. falciparum NF-54 gametocytes to evaluate the parasite-boosting effect on r Pvs 48/45 antibody titers. Specific anti- rPvs 48/45 IgG purified from African sera was used to evaluate the ex vivo TB activity on P. falciparum, using standard mosquito membrane feeding assays (SMFA).
Results
r Pvs 48/45 protein showed cross-reactivity with sera of individuals from all four African countries, in proportions ranging from 94% (Tanzania) to 40% (Nigeria). Also, the level of cross-reactive antibodies varied significantly between countries (p<0.0001), with a higher antibody level in Mali and the lowest in Nigeria. In addition, antibody levels were higher in adults (≥ 17 years) than young children (≤ 5 years) in both Mali and Tanzania, with a higher proportion of responders in adults (90%) than in children (61%) (p<0.0001) in Mali, where male (75%) and female (80%) displayed similar antibody responses. Furthermore, immunization of mice with P. falciparum gametocytes boosted anti- Pvs 48/45 antibody responses, recognizing P. falciparum gametocytes in indirect immunofluorescence antibody test. Notably, r Pvs 48/45 affinity-purified African IgG exhibited a TB activity of 61% against P. falciparum in SMFA.
Conclusion
African sera (exposed only to P. falciparum) cross-recognized the r Pvs 48/45 protein. This, together with the functional activity of IgG, warrants further studies for the potential development of a P. vivax and P. falciparum cross-protective TB vaccine.
