Intranasal trans-sialidase-based vaccine against Trypanosoma cruzi triggers a mixed cytokine profile in the nasopharynx-associated lymphoid tissue and confers local and systemic immunogenicity

PACINI, MARÍA F.; BALBI, CAMILA BULFONI; DINATALE, BRENDA; GONZÁLEZ, FLORENCIA B.; PROCHETTO, ESTEFANIA; DE HERNÁNDEZ, MARÍA A.; CRIBB, PAMELA; FARRÉ, CECILIA; ESPARIZ, MARTÍN; BLANCATO, VÍCTOR S.; MAGNI, CHRISTIAN; MARCIPAR, IVÁN; PÉREZ, ANA R.; COLABORACIÓN TÉCNICA: MARISA E. DERIO

ACTA TROPICA

ELSEVIER SCIENCE BV

Año: 2023 vol. 241

0001-706X

Trypanosoma cruzi, the agent of Chagas disease, can infect through conjunctive or oral mucosas. Therefore, theinduction of mucosal immunity by vaccination is relevant not only to trigger local protection but also to stimulateboth humoral and cell-mediated responses in systemic sites to control parasite dissemination. In a previousstudy, we demonstrated that a nasal vaccine based on a Trans-sialidase (TS) fragment plus the mucosal STINGagonist c-di-AMP, was highly immunogenic and elicited prophylactic capacity. However, the immune profileinduced by TS-based nasal vaccines at the nasopharyngeal-associated lymphoid tissue (NALT), the target site ofnasal immunization, remains unknown. Hence, we analyzed the NALT cytokine expression generated by a TSbasedvaccine plus c-di-AMP (TSdA+c-di-AMP) and their association with mucosal and systemic immunogenicity.The vaccine was administered intranasally, in 3 doses separated by 15 days each other. Control groupsreceived TSdA, c-di-AMP, or the vehicle in a similar schedule. We demonstrated that female BALB/c miceimmunized intranasally with TSdA+c-di-AMP boosted NALT expression of IFN-γ and IL-6, as well as IFN-β andTGF-β. TSdA+c-di-AMP increased TSdA-specific IgA secretion in the nasal passages and also in the distal intestinalmucosa. Moreover, T and B-lymphocytes from NALT-draining cervical lymph nodes and spleen showedan intense proliferation after ex-vivo stimulation with TSdA. Intranasal administration of TSdA+c-di-AMP provokesan enhancement of TSdA-specific IgG2a and IgG1 plasma antibodies, accompanied by an increase IgG2a/IgG1 ratio, indicative of a Th1-biased profile. In addition, immune plasma derived from TSdA+c-di-AMPvaccinated mice exhibit in-vivo and ex-vivo protective capacity. Lastly, TSdA+c-di-AMP nasal vaccine also promotesintense footpad swelling after local TSdA challenge. Our data support that TSdA+c-di-AMP nasal vaccinetriggers a NALT mixed pattern of cytokines that were clearly associated with an evident mucosal and systemicimmunogenicity. These data are useful for further understanding the immune responses elicited by the NALTfollowing intranasal immunization and the rational design of TS-based vaccination strategies for prophylaxisagainst T. cruzi.