Vacinologia reversa de candidatos contra vetores parasitiformes e agentes causadores de febre maculosa das Américas

Abstract

Spotted fever is a rapidly progressive infection caused by bacterias of the genus Rickettsia. In the Americas, up to 80% of symptomatic human cases progress to death. In animals, the disease can also evolve to severe forms, with special emphasis on dogs among domestic animals. The rickettsias that cause this disease are mostly transmitted by ticks, whose greatest diversity of transmission species belong to the genus Amblyomma. Recent trials have shown that there are already promising vaccine targets from these rickettsias. However, there are still no vaccines for people or vaccines that simultaneously protect humans and animals against all forms of the disease. Importantly, certain salivary antigens of hematophagous arthropods are capable of inducing host immune response, not only against the vector, but also against certain transmitted infectious agents. Thus, more effective vaccines against this disease are likely to be developed by combining antigens from both rickettsias and their transmitting arthropods. In an attempt to prospect vaccine antigens from both these pathogens and their parasitic vectors, this study proposed to survey the current diversity of antigenic proteins to be tested against Spotted Fever of the Americas (SFA) by Reverse Vaccinology. Primary protein sequences were selected and determined from transcriptomes and proteomes of clinically relevant agents and ticks for human disease in the American continent. With the help of innovative strategies for high-throughput arthropod transcript assembly and to refine screening target sequences, it was possible to show a high yield of vaccine candidates mainly for R. rickettsii (48) among the agents, and for A. americanum (17,641) among the SFA vectors. From 61 to 554 antigenic and shared salivary/intestinal targets were present among the vectors, while 21 bacterial antigens were found conserved among the analyzed rickettsias. Dozens of novel sequences similar to arthropod proteins and classified as antihemostatic, extracellular matrix, structural and developmental, microbial growth controllers and without defined function showed ≥ 90% antigenicity. More than 9 new antigens from rickettsias were identified, highlighting virulence factors, stabilizers of protein structures and sequences with domain of unknown function. Due to the limitations and disadvantages of existing diagnostic, treatment and preventive methods, combining the various candidates available and evaluating their efficacy in vitro and in vivo become necessary when developing more effective vaccines capable of preventing the evolution of SFA.