Nasal immunization with a L. lactis-derived trans-sialidase antigen plus c-di-AMP protects against acute oral T. cruzi infection

PACINI, MARIA FLORENCIA; GONZÁLEZ, FLORENCIA BELÉN; DINATALE, BRENDA; BULFONI BALBI, CAMILA; VILLAR, SILVINA RAQUEL; FARRÉ, CECILIA; LUPI, GIULIANA; ESPARIZ, MARTÍN; BLANCATO, VÍCTOR SEBASTIÁN; MAGNI, CHRISTIAN; MARCIPAR, IVÁN; ANA ROSA PÉREZ A,B,⇑; COLABORACIÓN TÉCNICA: MARISA E. DERIO

VACCINE

ELSEVIER SCI LTD

Año: 2022 vol. 40 p. 2311 - 2323

0264-410X

The new generation of vaccines for Chagas disease, are focused to induce both humoral and cellularresponse to effectively control Trypanosoma cruzi parasites. The administration of vaccine formulationsintranasally has the advantage over parenteral routes that can induce a specific response at mucosaland systemic levels. This study aimed to evaluate and compare the immunogenicity and prophylacticeffectiveness of two Trans-sialidase (TS)-based mucosal vaccines against T. cruzi administered intranasally.Vaccines consisted of a recombinant fragment of TS expressed in Lactococcus lactis formulated intwo different adjuvants. The first, was an immunostimulant particle (ISPA, an ISCOMATRIX-like adjuvant),while the second was the dinucleotide c-di-AMP, which have shown immunostimulant propertiesat the mucosal level. BALB/c mice were immunized intranasally (3 doses, one every two weeks) with eachformulation (TS + ISPA or TS + c-di-AMP) and with TS alone or vehicle (saline solution) as controls. Fifteendays after the last immunization, both TS + ISPA or TS + c-di-AMP induced an evident systemic humoraland cellular response, as judged by the increased plasma anti-TS IgG2a titers and IgG2a/IgG1 ratio andenhanced cellular response against TS. Plasma derived antibodies from TS + c-di-AMP also inhibitin vitro the invasion capacity of T. cruzi. Furthermore, specific secretory IgA was more enhanced inTS + c-di-AMP group. Protective efficacy was proved in vaccinated animals by an oral T. cruzichallenge.Parasitemia control was only achieved by animals vaccinated with TS + c-di-AMP, despiteall vaccinates groups showed enhanced CD8+IFN-c+ T cell numbers. In addition, it was reflected duringthe acute phase in a significant reduction of tissue parasite load, clinical manifestations and diminishedtissue damage. The better prophylactic capacity elicited by TS + c-di-AMP was related to the induction ofneutralizing plasma antibodies and augmented levels of mucosal IgA since TS + ISPA and TS + c-di-AMPgroups displayed similar immunogenicity and CD8+IFN-c+ T-cell response. Therefore, TS + c-di-AMP formulationappears as a promising strategy for prophylaxis against T. cruzi.