The Schistosoma mansoni cyclophilin A epitope 107-121 induces a protective immune response against schistosomiasis

Abstract

Great efforts have been made to identify promising antigens and vaccine formulations against schistosomiasis. Among the previously described Schistosoma vaccine candidates, cyclophilins comprise an interesting antigen that could be used for vaccine formulations. Cyclophilin A is the target for the cyclosporine A, a drug with schistosomicide activity, and its orthologue from Schistosoma japonicum induces a protective immune response in mice. Although Schistosoma mansoni cyclophilin A also represents a promising target for anti-schistosome vaccines, its potential to induce protection has not been evaluated. In this study, we characterized the cyclophilin A (SmCyp), initially described as Smp17.7, analyzed its allergenic potential using in vitro functional assays, and evaluated its ability to induce protection in mice when administered as an antigen using different vaccine formulations and strategies. Results indicated that SmCyp could be successfully expressed by mammalian cells and bacteria.The recombinant protein did not promote IgE-reporter system activation in vitro, demonstrating its probable safety for use in vaccine formulations. T and B-cell epitopes were predicted in the SmCyp sequence, with two of them located within the active isomerase site. The most immunogenic antigen, SmCyp (107-121), was then used for immunization protocols. Immunization with the SmCyp gene or protein failed to reduce parasite burden but induced an immune response that modulated the granuloma area. In contrast, immunization with the synthetic peptide SmCyp (107-121) significantly reduced worm burden (48-50%) in comparison to control group, but did not regulate liver pathology. Moreover, the protection observed in mice immunized with the synthetic peptide was associated with the significant production of antibodies against the SmCyp (107-121) epitope. Therefore, in this study, we identified an epitope within the SmCyp sequence that induces a protective immune response against the parasite, thus representing a promising antigen that could be used for vaccine formulation against schistosomiasis.

Doenças infecciosas e parasitárias no contexto brasileiro

“…A produção de vacinas é um grande desafio, além do cuidado com os antígenos alergênicos que poderiam causar uma reação autoimune, deve-se encontrar a composição primordial capaz de induzir uma resposta imune suficiente para ocasionar a proteção (MELO et al, 2019;RANASINGHE et al, 2018). Ao longo dos anos, diversos antígenos candidatos foram estudados para a produção de uma vacina eficaz.…”

“…Nas formulações estudadas por Assis et al (2015), as vacinas não obtiveram porcentagens de redução muito elevadas, porém conseguiram reduzir a área de granuloma, provavelmente devido a produção de TNF-α e IFN-γ (ASSIS et al, 2015). Já na SmCyp de DNA não houve nenhuma redução considerável em relação a SmCyp [107][108][109][110][111][112][113][114][115][116][117][118][119][120][121], que apresentou alta redução na carga de vermes e ovos, provavelmente devido a parte do peptídeo selecionada (MELO et al, 2019). A vacina SmKI-1, produziu IL-6 que reduz a patologia da doença protegendo contra a hipertensão pulmonar, além de ocasionar a diferenciação de Th2, compensando o equilíbrio entre Th1/Th2, entretanto manteve a redução na carga de vermes e ovos abaixo dos 40% preconizados pela OMS (RANASINGHE et al, 2018).…”

“…Outrossim, Melo et al (2019) MELO et al, 2019). Por outro lado, Ranasinghe et al (2018) realizaram um estudo com uma vacina SmKI-1 onde obteve redução na carga de vermes (23-33%), na carga de ovos no fígado (20-43%), no intestino (28-31%) e nos ovos fecais (33-39%).…”

Are humanized IgE reporter systems potential game changers in serological diagnosis of human parasitic infection?

“…RS-ATL8 cells are extremely sensitive, allowing detection of as little as 15 pg/ mL of IgE, 0.04 to 0.4 ng/mL allergen-specific IgE, or as little as 1 fg/mL of egg allergen using sera from egg-allergic patients. We later were able to demonstrate the suitability of RS-ATL8 cells in the context of Schistosoma mansoni infection (Wan et al 2014a) and vaccine candidate screening (de Melo et al 2019). Due to their unrivaled sensitivity, using IgE reporter systems for detection of specific IgE has many advantages but also some drawbacks, both summarized in Table 1.…”

The Humanised NPY-mRFP RBL Reporter Cell Line Is a Fast and Inexpensive Tool for Detection of Allergen-Specific IgE in Human Sera

“…The advantages and disadvantages of RBL-based, humanised IgE reporters have been discussed in detail before [ 3 , 11 ]. Humanised IgE reporter systems have been used to elucidate an intriguing ‘outbreak’ of allergy to wheat hydrolysate containing cosmetic products in Japan [ 12 , 13 ], for the assessment of potential allergenicity of anti-helminthic vaccine candidates [ 14 ], to identify exposure to Ascaris lumbricoides as a potential cause underlying red meat allergy (Alpha-Gal sensitisation) [ 15 ] or to identify potential new allergens in black tiger shrimps [ 16 ], with another group suggesting that they may be superior to conventional diagnostic allergy tests in the case of shrimp allergy [ 17 ]. Here, we describe the generation and use of a faster, convenient new humanised fluorescent IgE reporter system, which does not require addition of any substrate and is, therefore, suitable for use in, e.g., high-throughput screening assays.…”