Naturally acquired antibody response to a Plasmodium falciparum chimeric vaccine candidate GMZ2.6c and its components (MSP-3, GLURP, and Pfs48/45) in individuals living in Brazilian malaria-endemic areas

Malaria Journal

Michael Theisen¹  Susheel Kumar Singh¹  João Hermínio Martins da Silva²  Linda Eva Amoah³  Rodrigo Medeiros Souza⁴  Josué Costa Lima-Junior⁵  Marcelo Ribeiro-Alves⁶  Barbara Oliveira Baptista⁷  Lilian Rose Pratt-Riccio⁷  Cesare Bianco-Junior⁷  Paulo Renato Rivas Totino⁷  Cláudio Tadeu Daniel-Ribeiro⁷  Ana Beatriz Lopes de Souza⁷  Evelyn Kety Pratt Riccio⁷ 

[1]Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

[2]Departamento de Bioinformática, Fiocruz, Ceará, Brazil

[3]Immunology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra, Ghana

[4]Laboratório de Doenças Infecciosas na Amazônia Ocidental, Universidade Federal do Acre, Acre, Brazil

[5]Laboratório de Imunoparasitologia, IOC, Rio de Janeiro, Fiocruz, Brazil

[6]Laboratório de Pesquisa Clínica em DST e AIDS, Instituto Nacional de Infectologia Evandro Chagas, Fiocruz, Rio de Janeiro, Brazil

[7]Laboratório de Pesquisa em Malária, Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, Brazil

[8]Centro de Pesquisa, Diagnóstico e Treinamento em Malária, Fiocruz, Secretaria de Vigilância em Saúde, Ministério da Saúde, Brazil

关键词: Malaria;    Plasmodium falciparum;    Immune response;    Antibodies;    GMZ2.6c;    Vaccine;   

DOI  :  10.1186/s12936-021-04020-6

来源: Springer

【 摘 要 】

BackgroundThe GMZ2.6c malaria vaccine candidate is a multi-stage Plasmodium falciparum chimeric protein which contains a fragment of the sexual-stage Pfs48/45-6C protein genetically fused to GMZ2, a fusion protein of GLURP and MSP-3, that has been shown to be well tolerated, safe and immunogenic in clinical trials performed in a malaria-endemic area of Africa. However, there is no data available on the antigenicity or immunogenicity of GMZ2.6c in humans. Considering that circulating parasites can be genetically distinct in different malaria-endemic areas and that host genetic factors can influence the immune response to vaccine antigens, it is important to verify the antigenicity, immunogenicity and the possibility of associated protection in individuals living in malaria-endemic areas with different epidemiological scenarios. Herein, the profile of antibody response against GMZ2.6c and its components (MSP-3, GLURP and Pfs48/45) in residents of the Brazilian Amazon naturally exposed to malaria, in areas with different levels of transmission, was evaluated.MethodsThis study was performed using serum samples from 352 individuals from Cruzeiro do Sul and Mâncio Lima, in the state of Acre, and Guajará, in the state of Amazonas. Specific IgG, IgM, IgA and IgE antibodies and IgG subclasses were detected by Enzyme-Linked Immunosorbent Assay.ResultsThe results showed that GMZ2.6c protein was widely recognized by naturally acquired antibodies from individuals of the Brazilian endemic areas with different levels of transmission. The higher prevalence of individuals with antibodies against GMZ2.6c when compared to its individual components may suggest an additive effect of GLURP, MSP-3, and Pfs48/45 when inserted in a same construct. Furthermore, naturally malaria-exposed individuals predominantly had IgG1 and IgG3 cytophilic anti-GMZ2.6c antibodies, an important fact considering that the acquisition of anti-malaria protective immunity results from a delicate balance between cytophilic/non-cytophilic antibodies. Interestingly, anti-GMZ2.6c antibodies seem to increase with exposure to malaria infection and may contribute to parasite immunity.ConclusionsThe data showed that GMZ2.6c protein is widely recognized by naturally acquired antibodies from individuals living in malaria-endemic areas in Brazil and that these may contribute to parasite immunity. These data highlight the importance of GMZ2.6c as a candidate for an anti-malarial vaccine.

【 授权许可】

CC BY