Rectal Administration of Leishmania Cells Elicits a Specific, Th1-Associated IgG2a Response in Mice: New Perspectives for Mucosal Vaccination against Leishmaniasis, after the Repurposing of a Study on an Anti-Viral Vaccine Candidate

Abstract

The mucosal immune system plays a pivotal role in the control of infections, as it represents the first line of defense against most pathogens, from respiratory viruses to intestinal parasites. Mucosal vaccination is thus regarded as a promising strategy to protect animals, including humans, from infections that are acquired by ingestion, inhalation or through the urogenital system. In addition, antigens delivered at the mucosal level can also elicit systemic immune responses. Therefore, mucosal vaccination is potentially effective also against systemic infections acquired through non-mucosal routes, for example, through the bite of hematophagous insects, as in the case of leishmaniasis, a widespread disease that affects humans and dogs. Here, we explored the potential of antigen rectal administration for the generation of anti-Leishmania immunity. Mice were immunized through rectal administration of whole cells of the model parasite Leishmania tarentolae (using a clone engineered to express the spike protein of the SARS-CoV-2 virus generated in a previous study). A specific anti-Leishmania IgG antibody response was detected. In addition, the recorded IgG2a/IgG1 ratio was higher than that of animals injected subcutaneously; therefore, suggesting a shift to a Th1-biased immune response. Considering the importance of a Th1 polarization as a protective response against Leishmania infections, we suggest that further investigation should be focused on the development of novel types of vaccines against these parasites based on rectal immunization.

Subcutaneous, Oral, and Intranasal Immunization of BALB/c Mice with Leishmania infantum K39 Antigen Induces Non-Protective Humoral Immune Response

“…Helou et al [30] report that the intranasal administration of L. donovani antigens was more effective than the intradermal route in inducing protection against visceral leishmaniasis in female BALB/c mice. Furthermore, the use of L. tarentolae antigens administered as a mucosal vaccine via the rectal route was able to activate a Th1 immune response profile, while the same antigen administered subcutaneously induced a Th2 response [29]. This brief report represents the first report of the humoral immune response induced by the K39 antigen of L. infantum, demonstrating its high immunogenicity via the subcutaneous, oral, and intranasal routes.…”

“…A promising strategy for protection against visceral leishmaniasis is the induction of systemic immune responses by antigens delivered to mucosal surfaces [ 29 , 30 ]. The major drawbacks of these immunization routes are the harsh gastrointestinal environment, which could lead to antigen degradation, and the possibility of inducing immunological tolerance [ 31 , 32 ].…”

“…Helou et al [ 30 ] report that the intranasal administration of L. donovani antigens was more effective than the intradermal route in inducing protection against visceral leishmaniasis in female BALB/c mice. Furthermore, the use of L. tarentolae antigens administered as a mucosal vaccine via the rectal route was able to activate a Th1 immune response profile, while the same antigen administered subcutaneously induced a Th2 response [ 29 ].…”