Efficacy of mucosal vaccination using a protozoan parasite as a vehicle for antigen delivery: IgG and neutralizing response after rectal administration of LeCoVax-2, a candidate vaccine against COVID-19

Epis, Sara; Varotto-Boccazzi, Ilaria; Manenti, Alessandro; Rubolini, Diego; Gabrieli, Paolo; Cattaneo, Giulia Maria; Gourlay, L.J.; Dapporto, Francesca; Monti, Martina; Razzano, Ilaria; Leonardi, Margherita; Iannacone, Matteo; Recordati, Camilla; Bertola, Luca; Fiorina, Paolo; Marvasi, Luigi; Montomoli, Emanuele; Zuccotti, Gianvincenzo; Bandi, Claudio

doi:10.1016/j.phrs.2022.106546

Cited by 4 publications

(8 citation statements)

References 38 publications

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“…In addition, mice immunized through the rectal route with LeCoVax-2 + R84825 also showed statistically significant differences compared to the controls ( p < 0.05) ( Figure 1 A). Interestingly, mice that showed antibodies against Leishmania were the same that produced antibodies against SARS-CoV-2 in the previous study ( Table 1 ) [ 13 ], except for two animals (from the subcutaneous group) that developed only antibodies against Leishmania . Overall, a positive correlation between the two responses (i.e., against SARS-CoV-2 and Leishmania spp.)…”

Section: Resultsmentioning

confidence: 72%

“…The purpose of the current study was to explore whether rectal administration of whole, inactivated cells from L. tarentolae is suitable to induce a specific antibody response against L. tarentolae itself. To perform this study, we took advantage from a previous study, in which whole cells of L. tarentolae (from the clone Lt-spike) had been administered to BALB/c mice through the rectal route, with the purpose of assaying a candidate vaccine against COVID-19 (see [ 13 ] and Material and Methods section). The aim of this previous study was to determine the response against SARS-CoV-2; determination of anti- Leishmania antibody production was thus not performed.…”

Section: Resultsmentioning

confidence: 99%

“…This positive correlation suggests that variability of the response of mice in the groups intrarectally immunized may be due to the characteristics of the route of administration. As discussed in [ 13 ], rectal vaccination implies that the retention of the antigen in the intestine is variable, in some way unpredictable, and this can explain the variability of the results obtained after vaccination through this route.…”

Section: Resultsmentioning

confidence: 99%

“…In a previous study, L. tarentolae was engineered to express the spike protein antigen from SARS-CoV-2 [ 13 ]. The engineered clone of L. tarentolae (Lt-spike) was then used to prepare a candidate anti-COVID-19 vaccine that was tested in immunization assays in mice.…”

Section: Methodsmentioning

confidence: 99%

“…To perform this study, we used sera samples derived from a previous experiment ([ 13 ]; authorizations: D4A18.B.1YW; D4A18.B.FX6), in which female BALB/c mice were immunized with LeCoVax-2. The animals were used according to Directive 2010/63/UE regarding the protection of animals used for experimental or other scientific purposes, enforced by the Italian Legislative Decree n° 26 of 2014 and Ministerial.…”

Section: Methodsmentioning

confidence: 99%

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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

Varotto-Boccazzi,

Epis,

Cattaneo

et al. 2023

TropicalMed

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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.

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Section: Resultsmentioning

confidence: 72%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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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

Varotto-Boccazzi,

Epis,

Cattaneo

et al. 2023

TropicalMed

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Intracellular persistence of Leishmania tarentolae in primary canine macrophage cells

et al. 2023

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Leishmania tarentolae: a vaccine platform to target dendritic cells and a surrogate pathogen for next generation vaccine research in leishmaniases and viral infections

et al. 2023

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Parasites of the genus Leishmania are unusual unicellular microorganisms in that they are characterized by the capability to subvert in their favor the immune response of mammalian phagocytes, including dendritic cells. Thus, in overt leishmaniasis, dendritic cells and macrophages are converted into a niche for Leishmania spp. in which the parasite, rather than being inactivated and disassembled, survives and replicates. In addition, Leishmania parasites hitchhike onto phagocytic cells, exploiting them as a mode of transport to lymphoid tissues where other phagocytic cells are potentially amenable to parasite colonization. This propensity of Leishmania spp. to target dendritic cells has led some researchers to consider the possibility that the non-pathogenic, reptile-associated Leishmania tarentolae could be exploited as a vaccine platform and vehicle for the production of antigens from different viruses and for the delivery of the antigens to dendritic cells and lymph nodes. In addition, as L. tarentolae can also be regarded as a surrogate of pathogenic Leishmania parasites, this parasite of reptiles could possibly be developed into a vaccine against human and canine leishmaniases, exploiting its immunological cross-reactivity with other Leishmania species, or, after its engineering, for the expression of antigens from pathogenic species. In this article we review published studies on the use of L. tarentolae as a vaccine platform and vehicle, mainly in the areas of leishmaniases and viral infections. In addition, a short summary of available knowledge on the biology of L. tarentolae is presented, together with information on the use of this microorganism as a micro-factory to produce antigens suitable for the serodiagnosis of viral and parasitic infections. Graphical Abstract

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Efficacy of mucosal vaccination using a protozoan parasite as a vehicle for antigen delivery: IgG and neutralizing response after rectal administration of LeCoVax-2, a candidate vaccine against COVID-19

Cited by 4 publications

References 38 publications

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

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

Intracellular persistence of Leishmania tarentolae in primary canine macrophage cells

Leishmania tarentolae: a vaccine platform to target dendritic cells and a surrogate pathogen for next generation vaccine research in leishmaniases and viral infections

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