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Elucidating mechanisms of action of multicomponent anti-tick vaccines with different efficacies

Grant number: 22/13778-9
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): February 28, 2023
Effective date (End): January 27, 2024
Field of knowledge:Biological Sciences - Immunology - Applied Immunology
Principal Investigator:Isabel Kinney Ferreira de Miranda Santos
Grantee:Thales Eduardo Galdino Andrade
Supervisor: Andrew Barrett Ward
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Research place: Scripps Research Institute, San Diego, United States  
Associated to the scholarship:21/11245-0 - Evaluation of the vaccine-induced immunity of a formulation based on multiple epitopes of salivary gland proteins of ticks Rhipicephalus microplus, BP.DR

Abstract

Vaccines prime barriers of the immune system to hinder progress of infection to disease. However, traditional strategies have not been successful against certain pathogens. Regarding the control of the cattle tick Rhipicephalus microplus, an ectoparasite with multiple mechanisms of parasitism based on highly varied antigens that evade its hosts' defenses, so far, no vaccine has achieved an efficacy compatible with productivity and lasting immunological memory. Our group has identified and tested multiple proteins derived from this parasite's salivary glands, so-called exposed antigens, with the potential to induce antibodies that neutralize parasitism in all of its life stages. In our last trial, with two fermentation processes we obtained and tested six recombinant chimeras formed by 13 complete salivary antigens coupled with linkers and connected to a tag containing helper T cell epitopes. These chimeras provided an overall efficacy of more than 90% (i.e., reducing ticks loads, conversion of blood meals to egg masses and eclosion rates of eggs). In the same trial we tested six chimeras formed by the same 13 salivary antigens, but truncated with domain minimization, and two chimeras formed by all of the linear B cell epitopes (BCLs) predicted with BebiPred for 15 salivary proteins. The chimeras of truncated antigens provided only 20% efficacy and the chimeras of BCLs provided 70% efficacy. All chimeras were immunogenic, but induced lower antibody titers than those induced in animals receiving 15 individual recombinant antigens. The mechanisms involved in these effects of variable efficacy and immunogenicity need to be elucidated. Cryo-electron microscopy is the basis of structural vaccinology and has been recently improved to investigate the dynamics of polyclonal antibody responses after immunization (EMPEM, epitope mapping with polyclonal sera and electron microscopy). This technique evaluates surfaces of immunogens in order to determine the epitopes involved protective antibody responses. This project applies EMPEM to describe at a molecular level the immunogenic features of our antigens and chimeric vaccines against R. microplus, correlate them with efficacies and identify with greater precision the epitopes that are effectively involved in the impairment of tick parasitism. (AU)

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