Generation and analysis of the immunogenicity of recombinant proteins based on the different allelic forms of the circumsporozoite antigen of Plasmodium vivax aiming at the development of a universal vaccine against malaria

• Grant number: 12/13032-5
• Support Opportunities: Research Projects - Thematic Grants
• Duration: February 01, 2014 - January 31, 2025
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Irene da Silva Soares
• Grantee: Irene da Silva Soares
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Pesquisadores principais: Irene da Silva Soares
• Associated researchers: Daniel Youssef Bargieri ; Eduardo Lani Volpe da Silveira ; Hildegund C.J. Ertl ; Karina Ramalho Bortoluci ; Luis Carlos de Souza Ferreira ; Ruth Nussenzweig ; Victor Nussenzweig
• Associated scholarship(s): 23/15071-2 - Evaluation of the IgG antibody response against different allelic forms of the Plasmodium vivax circumsporozoite protein in sera from individuals from malaria endemic areas, BP.IC; 22/04180-2 - Evaluation of the IgG isotype profile in mice induced by immunization with Plasmodium vivax multi-antigen based formulations, BP.IC; 22/03587-1 - Evaluation of the affinity antibodies induced by Plasmodium vivax multi-antigen based formulations in mice, BP.IC; + associated scholarships 19/25373-0 - Influence of the proteic-energetic malnutrution in the humoral e cellular immune responses elicited by a malaria vaccine in C57Bl/6 mice, BP.IC; 19/06494-1 - Comparative analysis between the humoral and cellular immune responses elicited by a malaria vaccine adjuvanted with poly I:C or alum in C57BL/6 mice, BP.IC; 18/17364-9 - Evaluation of the immunogenicity of novel multi-stage recombinant proteins candidates for the development of a vaccine to Plasmodium vivax, BP.PD; 17/04079-1 - Expression and purification of allelic variants of Plasmodium vivax Apical Membrane Antigen 1 (AMA-1) aiming to immunological studies, BP.IC; 14/18102-7 - Preclinical tests of recombinant adenovirus-based protein and vaccine formulations expressing the Plasmodium vivax circumsporozoite protein, BP.PD - associated scholarships

Abstract

Plasmodium vivax is the second most prevalent species causing malaria in the world. Recent data estimated 132-391 million cases annually. The relative inefficiency of the measures of control currently used demands the development of new strategies for prevention such as vaccines, new drugs and insecticides. In last the 15 years, studies aimed at the development of a recombinant vaccine against the human malaria caused by the deadly parasite Plasmodium falciparum were based on the circumsporozoite (CS) antigen. In a recent publication, phase III trials in African children reported 50% efficacy. Based on the studies with P. falciparum, our previous FAPESP thematic project aimed at the generation of recombinant proteins and adenoviruses based on the primary sequences representing the different allelic variants of P. vivax CS protein. These recombinant proteins and adenovirus were used successfully in protocols of heterologous prime-boost (adenovirus/recombinant protein) vaccination in experimental mouse model. These recombinants and the respective protocol of vaccination were object of a patent application recently submitted to the United States Patent and Trademark Office ("Plasmodium vivax vaccine compositions 27522-0201WO1"). In the present project, it will be our goal to continue our studies aimed at the development of a universal vaccine against the P. vivax. We will produce new recombinant proteins and use for production of the antigens in cGMP conditions. These recombinant antigens/adenoviruses will be analyzed in its toxicity and immunogenicity for its subsequent use in phase I clinical trials. (AU)

Scientific publications

(16)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ROCHA, MARIANA VILELA; FRANCOSO, KATIA SANCHES; LIMA, LUCIANA CHAGAS; CAMARGO, TARSILA MENDES; MACHADO, RICARDO L. D.; COSTA, FABIO T. M.; RENIA, LAURENT; NOSTEN, FRANCOIS; RUSSELL, BRUCE; RODRIGUES, MAURICIO M.; et al. Generation, characterization and immunogenicity of a novel chimeric recombinant protein based on Plasmodium vivax AMA-1 and MSP1(19). Vaccine, v. 35, n. 18, p. 2463-2472, APR 25 2017. (12/13032-5, 11/23278-9, 13/01487-0)

SILVEIRA, EDUARDO L. V.; DOMINGUEZ, MARIANA R.; SOARES, IRENE S.. To B or Not to B: Understanding B Cell Responses in the Development of Malaria Infection. FRONTIERS IN IMMUNOLOGY, v. 9, DEC 14 2018. (12/13032-5, 17/11931-6)

MORROT, ALEXANDRE; RODRIGUES, MAURICIO M.. Tissue signatures influence the activation of intrahepatic CD8(+) T cells against malaria sporozoites. FRONTIERS IN MICROBIOLOGY, v. 5, AUG 22 2014. (12/13032-5)

VICENTIN, ELAINE C.; FRANCOSO, KATIA S.; ROCHA, MARIANA V.; IOURTOV, DMITRI; DOS SANTOS, FERNANDA L.; KUBRUSLY, FLAVIA S.; SAKAUCHI, MARIA A.; RAW, ISAIAS; NOSTEN, FRANCOIS; RENIA, LAURENT; et al. Invasion-Inhibitory Antibodies Elicited by Immunization with Plasmodium vivax Apical Membrane Antigen-1 Expressed in Pichia pastoris Yeast. Infection and Immunity, v. 82, n. 3, p. 1296-1307, MAR 2014. (12/13032-5, 10/09893-0, 08/05613-2)

TEIXEIRA, LAIS H.; TARARAM, CIBELE A.; LASARO, MARCIO O.; CAMACHO, ARIANE G. A.; ERSCHING, JONATAN; LEAL, MONICA T.; HERRERA, SOCRATES; BRUNA-ROMERO, OSCAR; SOARES, IRENE S.; NUSSENZWEIG, RUTH S.; et al. Immunogenicity of a Prime-Boost Vaccine Containing the Circumsporozoite Proteins of Plasmodium vivax in Rodents. Infection and Immunity, v. 82, n. 2, p. 793-807, FEB 2014. (12/13032-5)

MARQUES, RODOLFO F.; GIMENEZ, ALBA MARINA; ALIPRANDINI, EDUARDO; NOVAIS, JANAINA T.; CURY, DIEGO P.; WATANABE, II-SEI; DOMINGUEZ, MARIANA R.; SILVEIRA, EDUARDO L. V.; AMINO, ROGERIO; SOARES, IRENE S.. Protective Malaria Vaccine in Mice Based on the Plasmodium vivax Circumsporozoite Protein Fused with the Mumps Nucleocapsid Protein. VACCINES, v. 8, n. 2, JUN 2020. (12/13032-5, 14/18102-7)

GIMENEZ, ALBA MARINA; SALMAN, AHMED M.; MARQUES, RODOLFO F.; LOPEZ-CAMACHO, CESAR; HARRISON, KATE; KIM, YOUNG CHAN; JANSE, CHRIS J.; SOARES, IRENE S.; REYES-SANDOVAL, ARTURO. A universal vaccine candidate against Plasmodium vivax malaria confers protective immunity against the three PvCSP alleles. SCIENTIFIC REPORTS, v. 11, n. 1, SEP 9 2021. (12/13032-5, 16/26123-0, 14/18102-7)

MARQUES, RODOLFO F.; DE MELO, FILIPE MENEGATTI; NOVAIS, JANAINA TENORIO; SOARES, IRENE S.; BARGIERI, DANIEL YOUSSEF; GIMENEZ, ALBA MARINA. Immune System Modulation by the Adjuvants Poly (I:C) and Montanide ISA 720. FRONTIERS IN IMMUNOLOGY, v. 13, p. 14-pg., 2022-06-29. (12/13032-5, 18/25993-6, 14/18102-7, 21/04455-9)

DOBRESCU, IRINA; DE CAMARGO, TARSILA MENDES; GIMENEZ, ALBA MARINA; MURILLO, OSCAR; AMORIM, KELLY NAZARE DA SILVA; MARINHO, CLAUDIO ROMERO FARIAS; SOARES, IRENE SILVA; BOSCARDIN, SILVIA BEATRIZ; BARGIERI, DANIEL YOUSSEF. Protective Immunity in Mice Immunized With P. vivax MSP1(19)-Based Formulations and Challenged With P. berghei Expressing PvMSP1(19). FRONTIERS IN IMMUNOLOGY, v. 11, FEB 19 2020. (13/13119-6, 14/50631-0, 12/13032-5, 14/23083-1, 18/17364-9, 18/20468-0)

GIMENEZ, ALBA MARINA; LIMA, LUCIANA CHAGAS; FRANCOSO, KATIA SANCHES; DENAPOLI, PRISCILA M. A.; PANATIERI, RAQUEL; BARGIERI, DANIEL Y.; THIBERGE, JEAN-MICHEL; ANDOLINA, CHIARA; NOSTEN, FRANCOIS; RENIA, LAURENT; et al. Vaccine Containing the Three Allelic Variants of the Plasmodium vivax Circumsporozoite Antigen Induces Protection in Mice after Challenge with a Transgenic Rodent Malaria Parasite. FRONTIERS IN IMMUNOLOGY, v. 8, OCT 11 2017. (12/13032-5)

SALGADO-MEJIAS, PERLA; ALVES, FLAVIO L.; FRANCOSO, KATIA S.; RISKE, KARIN A.; SILVA, EMERSON R.; MIRANDA, ANTONIO; SOARES, IRENE S.. Structure of Rhoptry Neck Protein 2 is essential for the interaction in vitro with Apical Membrane Antigen 1 in Plasmodium vivax. Malaria Journal, v. 18, JAN 25 2019. (12/17060-3, 12/13032-5)

ERSCHING, JONATAN; BASSO, ALEXANDRE SALGADO; GARCIA KALICH, VERA LUCIA; BORTOLUCI, KARINA RAMALHO; RODRIGUES, MAURICIO M.. A Human Trypanosome Suppresses CD8(+) T Cell Priming by Dendritic Cells through the Induction of Immune Regulatory CD4(+) Foxp3(+) T Cells. PLOS PATHOGENS, v. 12, n. 6, JUN 2016. (12/13032-5, 09/06820-4, 12/22514-3)

DE CAMARGO, TARSILA MENDES; DE FREITAS, ELISANGELA OLIVEIRA; GIMENEZ, ALBA MARINA; LIMA, LUCIANA CHAGAS; CARAMICO, KARINA DE ALMEIDA; FRANCOSO, KATIA SANCHES; BRUNA-ROMERO, OSCAR; ANDOLINA, CHIARA; NOSTEN, FRANCOIS; RENIA, LAURENT; et al. Prime-boost vaccination with recombinant protein and adenovirus-vector expressing Plasmodium vivax circumsporozoite protein (CSP) partially protects mice against Pb/Pv sporozoite challenge. SCIENTIFIC REPORTS, v. 8, JAN 18 2018. (12/13032-5, 09/15099-7, 14/18102-7)

STAN, RAZVAN C.; FRANCOSO, KATIA S.; ALVES, RUBENS P. S.; FERREIRA, LUIS CARLOS S.; SOARES, IRENE S.; DE CAMARGO, MARISTELA M.. Febrile temperatures increase in vitro antibody affinity for malarial and dengue antigens. PLoS Neglected Tropical Diseases, v. 13, n. 4, APR 2019. (11/51778-6, 12/13032-5, 14/17595-0, 16/20045-7)

LIMA, LUCIANA C.; MARQUES, RODOLFO F.; GIMENEZ, ALBA MARINA; FRANCOSO, KATIA S.; ALIPRANDINI, EDUARDO; CAMARGO, TARSILA M.; AGUIAR, ANNA CAROLINE C.; PEREIRA, DHELIO B.; RENIA, LAURENT; AMINO, ROGERIO; et al. A Multistage Formulation Based on Full-Length CSP and AMA-1 Ectodomain ofPlasmodium vivaxInduces High Antibody Titers and T-cells and Partially Protects Mice Challenged with a TransgenicPlasmodium bergheiParasite. MICROORGANISMS, v. 8, n. 6, JUN 2020. (12/13032-5, 14/18102-7, 18/17364-9)

FRANCA, ANA CAROLINE BARBOSA; FRANCOSO, KATIA SANCHES; MARQUES, RODOLFO FERREIRA; TROSSINI, GUSTAVO H. G.; GOMES, RENAN A.; POVOA, MARINETE M.; CUNHA, MARISTELA G.; SILVEIRA, EDUARDO L. V.; SOARES, IRENE S.. Antibodies Against the Plasmodium vivax Apical Membrane Antigen 1 From the Belem Strain Share Common Epitopes Among Other Worldwide Variants. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 11, MAR 16 2021. (12/13032-5, 16/50108-0)