Development of multi-antigenic vaccine candidates against Rhipicephalus microplus ticks, evaluation of their efficacy and the induced immune response in bovines

• Grant number: 22/07400-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2022
• End date: March 01, 2026
• Field of knowledge: Biological Sciences - Parasitology
• Principal Investigator: Beatriz Rossetti Ferreira
• Grantee: Alexsander de Moraes
• 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): 23/17939-0 - Generation of mono-allelic BoLA-DRB3 bovine cell lines, immunopeptidomic characterization, and development of NetBoLAIIpan to advance CD4+ T cell epitope mapping and vaccine development, BE.EP.DR 23/14049-3 - Generation of mono-allelic BoLA-DRB3 bovine cell lines, immunopeptidomic characterization, and development of NetBoLAIIpan to advance CD4+ T cell epitope mapping and vaccine development, BE.EP.DR

Abstract

The tick Rhipicephalus microplus (cattle tick) is an obligate hematophagous arthropod, known worldwide for infesting cattle and causing potentially lethal diseases such as cattle tick fever diseases. Such infestations and diseases affect bovine livestock activity, causing a worldwide economic impact estimated at about $18 billion/year, as they decrease meat and milk production and compromise the marketing of leather. Seeking to control these infestations, our group has developed effective vaccines against ticks based on ten salivary antigens, providing protection of up to 75% against R. microplus infestations in bovines. However, the large-scale commercial production of vaccines composed by several antigens is expensive, making them unfeasible. Therefore, in this project we propose the optimization of this vaccine through the development of new vaccine formulations composed by a) two chimeric immunizers obtained from the fusion between the ten protective antigens (five antigens per chimeric immunizer) and b) a single multi-epitope immunizer, composed by epitopes identified in the ten protective salivary antigens. Thus, we aim to obtain effective and commercially viable products that can be used as an anti-tick compound in bovine livestock production. We are currently conducting a clinical trial in dairy Holstein cattle to evaluate the protection against ticks provided by a vaccine formulation based on two recombinant chimeric antigens. Simultaneously, we have planned to construct multi-epitope antigens from previous data obtained by mapping B-cell epitopes in peptide microarray and phage display assays, and CD4 T-cell epitopes obtained by immunoinformatics. In addition, data on novel B-cell epitopes will be obtained in the current project via next-generation phage display. Such multi-epitope antigens will be tested in silico and in vivo for their immunogenic and protective potential, in order to identify the construct with the greatest vaccine potential. Finally, to gain a greater understanding of protection mechanisms induced by vaccine formulations, the humoral and cellular immune response induced by immunization of bovines will be evaluated.