Cross-reactivity of rPvs48/45, a recombinant Plasmodium vivax protein, with sera from Plasmodium falciparum endemic areas of Africa

Arevalo-Herrera, M.; Balam, S.; Miura, K.; Ayadi, I.; Konate, D.; Incandela, N. C.; Agnolon, V.; Guindo, M. A.; Diakite, S. A. S.; Olugbile, S.; Nebie, I.; Herrera, S. M.; Long, C.; Kajava, A. V.; Diakite, M.; Corradin, G.; Herrera, S.

doi:10.1101/2024.04.10.588966

bioRxiv · 10.1101/2024.04.10.588966

Cross-reactivity of rPvs48/45, a recombinant Plasmodium vivax protein, with sera from Plasmodium falciparum endemic areas of Africa

Arevalo-Herrera, M.·Balam, S.·Miura, K.·Ayadi, I.·Konate, D.·Incandela, N. C.·Agnolon, V.·Guindo, M. A.·Diakite, S. A. S.·Olugbile, S.·Nebie, I.·Herrera, S. M.·Long, C.·Kajava, A. V.·Diakite, M.·Corradin, G.·Herrera, S.

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Abstract

BackgroundPs48/45, 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 Ps48/45 protein (rPvs48/45) with sera from P. falciparum-exposed African donors. MethodsrPvs48/45 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 rPvs48/45 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 rPvs48/45 antibody titers. Specific anti-rPvs48/45 IgG purified from African sera was used to evaluate the ex vivo TB activity on P. falciparum, using standard mosquito membrane feeding assays (SMFA). ResultsrPvs48/45 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-Pvs48/45 antibody responses, recognizing P. falciparum gametocytes in indirect immunofluorescence antibody test. Notably, rPvs48/45 affinity-purified African IgG exhibited a TB activity of 61% against P. falciparum in SMFA. ConclusionAfrican sera (exposed only to P. falciparum) cross-recognized the rPvs48/45 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.

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Arevalo-Herrera, M., Balam, S., Miura, K., Ayadi, I., Konate, D., Incandela, N. C., Agnolon, V., Guindo, M. A., Diakite, S. A. S., Olugbile, S., Nebie, I., Herrera, S. M., Long, C., Kajava, A. V., Diakite, M., Corradin, G., Herrera, S.. 2024-04-15. Cross-reactivity of rPvs48/45, a recombinant Plasmodium vivax protein, with sera from Plasmodium falciparum endemic areas of Africa. https://doi.org/10.1101/2024.04.10.588966

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