Cross-reactivity of r48/45, a recombinant protein, with sera from endemic areas of Africa.

Background: 48/45, a 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 48/45 protein (r48/45) with sera from -exposed African donors.

Methods: r48/45 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 r48/45 protein formulated in Montanide ISA-51 and inoculated with a crude extract of NF-54 gametocytes to evaluate the parasite-boosting effect on r48/45 antibody titers. Specific anti-48/45 IgG purified from African sera was used to evaluate the TB activity on using standard mosquito membrane feeding assays (SMFA).

Results: r48/45 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 gametocytes boosted anti-48/45 antibody responses, recognizing gametocytes in indirect immunofluorescence antibody test. Notably, r48/45 affinity-purified African IgG exhibited a TB activity of 61% against in SMFA.

Conclusion: African sera (exposed only to cross-recognized the r48/45 protein. This, together with the functional activity of IgG, warrants further studies for the potential development of a and cross-protective TB vaccine.