Development of a recombinant multicomponent chimeric vaccine based in protein epitopes from Rhipicephalus microplus ticks

• Grant number: 18/23579-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2019
• End date: December 31, 2023
• Field of knowledge: Biological Sciences - Parasitology
• Principal Investigator: Beatriz Rossetti Ferreira
• Grantee: Andressa Fisch
• Host Institution: Escola de Enfermagem de Ribeirão Preto (EERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 15/09683-9 - Development of a recombinant multicomponent chimeric vaccine based in protein epitopes from Rhipicephalus microplus ticks, AP.TEM
• Associated scholarship(s): 22/02776-5 - Development and implementation of a BoLA-null cell system for immunopeptidomics characterisation of BoLA-DR ligands and production of a catalogue of predicted ligands from tick sialotranscriptomes for anti-tick vaccine development, BE.EP.PD

Abstract

Ticks are important vectors of diseases to humans and animals and promote significant losses in the cattle production sector, while also induce expressive inconvenience to dogs owners. The control of tick infestations has been done with acaricides, but the selection of resistant parasites and environmental contamination point towards the need for alternative methods of control. Currently available vaccines against ticks depict variable outcomes of protection against ticks within cattle herds and short lasting immunological memory, stimulating the research for more efficient vaccines. In this project we propose to carry out the construction of a recombinant protein consisting of epitopes derived from proteins of R. microplus selected by SPOT peptide synthesis technique. Initially, fifteen selected recombinant proteins will be produced and evaluated with regards to their potential to protect mice against challenge by R. sanguineus ticks. The proteins that impair biological and reproductive parameters of ticks will be used to inoculate dogs and bovines to produce immune sera that will be used for epitope mapping by SPOT technique. Thereby, specific regions of the proteins which induce immunity in both animal species will be identified and incorporated in the chimeric vaccine. Finally, the sequences of the reagent epitopes will be used for the synthesis of a recombinant chimeric protein, allowing expression of the fused epitopes in a single structure. The recombinant multicomponent chimeric protein will be used to immunize mice that subsequently will undergo a challenge infestation with R. sanguineus ticks, which will be evaluated in order to determine its efficiency as a vaccine and the humoral and cellular response. If the chimeric protein shows to be efficient in mice, an preliminary clinical trial will be performed on dogs and bovines.

Scientific publications

(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)

CONNELLEY, TIMOTHY; NICASTRI, ANNALISA; SHELDRAKE, TARA; VRETTOU, CHRISTINA; FISCH, ANDRESSA; REYNISSON, BIRKIR; BUUS, SOREN; HILL, ADRIAN; MORRISON, IVAN; NIELSEN, MORTEN; et al. Immunopeptidomic Analysis of BoLA-I and BoLA-DR Presented Peptides from Theileria parva Infected Cells. VACCINES, v. 10, n. 11, p. 35-pg., 2022-11-01. (17/21401-4, 18/23579-8)

FISCH, ANDRESSA; REYNISSON, BIRKIR; BENEDICTUS, LINDERT; NICASTRI, ANNALISA; VASOYA, DEEPALI; MORRISON, IVAN; BUUS, SOREN; FERREIRA, BEATRIZ ROSSETTI; SANTOS, ISABEL KINNEY FERREIRA DE MIRANDA; TERNETTE, NICOLA; et al. Integral Use of Immunopeptidomics and Immunoinformatics for the Characterization of Antigen Presentation and Rational Identification of BoLA-DR-Presented Peptides and Epitopes. JOURNAL OF IMMUNOLOGY, v. 206, n. 10, p. 2489-2497, MAY 15 2021. (18/23579-8, 15/09683-9, 17/21401-4)