Evaluation of the acquired immune responses to Plasmodium vivax VIR variant antigens in individuals living in malaria-endemic areas of Brazil

Abstract Background The naturally-acquired immune response to Plasmodium vivax variant antigens (VIR) was evaluated in individuals exposed to malaria and living in different endemic areas for malaria in the north of Brazil. Methods Seven recombinant proteins representing four vir subfamilies (A, B, C, and E) obtained from a single patient from the Amazon Region were expressed in Escherichia coli as soluble glutathione S-transferase fusion proteins. The different recombinant proteins were compared by ELISA with regard to the recognition by IgM, IgG, and IgG subclass of antibodies from 200 individuals with patent infection. Results The frequency of individuals that presented antibodies anti-VIR (IgM plus IgG) during the infection was 49%. The frequencies of individuals that presented IgM or IgG antibodies anti-VIR were 29.6% or 26.0%, respectively. The prevalence of IgG antibodies against recombinant VIR proteins was significantly lower than the prevalence of antibodies against the recombinant proteins representing two surface antigens of merozoites of P. vivax: AMA-1 and MSP119 (57.0% and 90.5%, respectively). The cellular immune response to VIR antigens was evaluated by in vitro proliferative assays in mononuclear cells of the individuals recently exposed to P. vivax. No significant proliferative response to these antigens was observed when comparing malaria-exposed to non-exposed individuals. Conclusion This study provides evidence that there is a low frequency of individuals responding to each VIR antigens in endemic areas of Brazil. This fact may explain the host susceptibility to new episodes of the disease.

This work was supported by a grant from the Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP). CFB, HADP, and ISS are supported by fellowships from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). TRO and MCSJ are supported by fellowships from FAPESP. The authors would like to thank Dr. Maristela Gomes da Cunha from Universidade Federal do Pará for support in the endemic area during the collect of samples for proliferation assays.

This work was supported by a grant from the Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP). CFB, HADP, and ISS are supported by fellowships from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). TRO and MCSJ are supported by fellowships from FAPESP. The authors would like to thank Dr. Maristela Gomes da Cunha from Universidade Federal do Pará for support in the endemic area during the collect of samples for proliferation assays.