Dados do Trabalho

Título

Protein epitope mapping for the rational design of a Schistosoma Vaccine: Insights from Human and Animal Studies

Introdução

A schistosomiasis vaccine would greatly aid in controlling and eliminating the disease. We advocate for the use of multiple immunogenic epitopes located at the host-parasite interface, which are associated with protective immune responses against schistosomes. In endemic areas, some individuals develop resistance to reinfection (RR), while others remain susceptible to reinfection (SR) after Praziquantel (PZQ) treatment.

Objetivo (s)

Study the immune responses from RR and SR individuals to identify epitopes associated with resistance for the rational design of a schistosome vaccine.

Material e Métodos

Sera collected from endemic areas individuals, 18 months after PZQ treatment (RR=9 / SR=8), were used to screen peptide microarrays containing 55 secreted or exposed proteins from the alimentary tract or tegument. Epitopes were considered when detected in a minimum of 3 individuals and comprised of at least 2 consecutive peptides. Additionally, we compared the identified epitopes with those previously mapped in protected animal models, including mice exposed to the attenuated cercarial vaccine and rhesus macaques exhibiting self-cure.

Resultados e Conclusão

A total of 100 epitopes were mapped regardless of the analyzed serum. The most reactive epitopes were identified within the proteins Sm25 and ADP-ribosyl cyclase (tegument), MEG-12, MEG-4.1 (esophageal gland), and LAMP (gastrodermis). The overall profile revealed that SR sera had higher reactivity towards proteins from the alimentary tract, whereas the RR group displayed higher reactivity against tegument targets. Notably, two tegument targets (Sm25 and ADP-ribosyl cyclase) displayed 3 distinct epitopes that were differentially recognized by the serum of RR individuals. In comparing epitopes mapped in humans with those identified in protected animal models, 71% were shared with mice and 20% with rhesus macaques. In conclusion, 3 epitopes from tegument proteins were preferentially recognized by RR after PZQ therapy. These epitopes were the most reactive epitopes among the tegument targets previously identified by the attenuated cercariae vaccine in the mouse model. Rhesus macaques exhibited fewer recognized and shared epitopes due to their lower exposure to the worm compared to the others, which had multiple exposures. These findings provide a list of peptides that are currently being investigated in the development of multiepitope vaccine constructs.

Palavras-chave

Schistosoma, epitopes, vaccine

Agradecimentos

Fiocruz VPPCB-007-FIO-18-2-45; PROEP/IGM/2020; CNPq 431155/2018-6; FAPESP 2017/24832-6