Intranasal Vaccination With Recombinant Human Adenovirus Encoding trans-Sialidase Gene Protects Mice From Lethal Subcutaneous and Oral Trypanosoma cruzi Challenges.

BACKGROUND

The majority of new cases of Chagas disease, caused by Trypanosoma cruzi, have been associated with oral infection. Thus, it is reasonable that any vaccine formulation developed should elicit systemic and mucosal immunity.

METHODS

Antigen-specific T-cell, B-cell, antibody-secreting cell, IgG, IgA, cytokine, and parasite DNA were assessed in Balb/c mice immunized with a recombinant adenovirus replication-deficient vector encoding the parasitic trans-sialidase (rAdTS) and challenged with T. cruzi trypomastigotes.

RESULTS

A 2-dose intranasal (IN) rAdTS administration protected mice from lethal subcutaneous and oral parasitic challenges, displaying lower parasitemia and higher survival than control mice. Although intramuscular (IM) rAdTS immunization seemed more immunogenic for CD4+ and CD8+ T cells, IN vaccinees presented the highest responses after parasite exposure. Oral parasitic challenge triggered differential cytokine and cytotoxic transcriptome profiles in the hearts of IM and IN vaccinees. IM and IN rAdTS vaccinations induced high TS-specific IgG and subclass titers in the serum, with predominance of IgG-secreting cells in the spleen and draining lymph nodes. Only IN vaccinees produced TS-specific IgA in mucosal tissues and serum, which showed inverse correlation with parasitemia in vivo. Serum samples from the IN rAdTS vaccinees significantly inhibited parasite invasion in vitro relative to IM counterparts. In addition, IN vaccinees had very low levels of parasite DNA in parasite-reservoir tissues upon oral parasitic challenge relative to IM counterparts.

CONCLUSIONS

IN rAdTS vaccination can effectively protect mice against acute Chagas disease caused by lethal distinct T. cruzi challenges, providing an interesting alternative for future vaccine clinical trials.