Self-adjuvanting C18 lipid vinil sulfone-PP2A vaccine: study of the induced immunomodulation against Trichuris muris infection.

M Gomez-Samblas,A M Espino,S Vilchez,F J Lopez-Jaramillo,D Bernal,F Santoyo-Gonzalez,F Bolás-Fernández,M Trelis,A Osuna,J J García-Rodríguez

doi:10.1098/rsob.170031

Abstract

Despite the importance of the adjuvant in the immunization process, very few adjuvants merge with the antigens in vaccines. A synthetic self-adjuvant oleic-vinyl sulfone (OVS) linked to the catalytic region of recombinant serine/threonine phosphatase 2A from the nematode Angiostrongylus costaricensis (rPP2A) was used for intranasal immunization in mice previously infected with Trichuris muris. The animal intranasal immunization with rPP2A-OVS showed a reduction of 99.01% in the number of the nematode eggs and 97.90% in adult. The immunohistochemical analysis of the intestinal sections showed that in immunized animals with lipopeptide the mucus was significantly higher than in the other experimental groups. Also, these animals presented significantly different chemokine, CCL20 and CCL11, levels. However, although the number and size of Tuft cells did not vary between groups, the intensity of fluorescence per cell was significant in the group immunized with the rPP2A-OVS. The results of the present study suggest that mice immunized with the lipopeptide are capable of activating a combined Th17/Th9 response. This strategy of immunization may be of great applicability not only in immunotherapy and immunoprophylaxis to control diseases caused by nematodes but also in pathologies necessitating action at the level of the Th9 response in the intestinal mucosa.

Highlights

Helminths have plagued human beings even before recorded history
A synthetic self-adjuvant oleic-vinyl sulfone (OVS) linked to the catalytic region of recombinant serine/threonine phosphatase 2A from the nematode Angiostrongylus costaricensis was used for intranasal immunization in mice previously infected with Trichuris muris
We have previously demonstrated that the catalytic region of the enzyme serine/threonine phosphatase 2A (PP2A), which is highly conserved among a large number of nematode species [9], is capable of inducing partial levels of protection against infections by diverse parasitic nematodes when administered by the mucosal route, intranasally, in mice and lambs

Summary

Introduction

It is estimated that roughly one-third of the almost 3 billion people who live on less than 2 USD per day in developing regions of sub-Saharan Africa, Asia and the Americas are infected with one or more species of helminths [1],. License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. Exacerbating poverty, malnutrition and anaemia as well as causing delays in the physical and intellectual development of infants [2], the most susceptible population. The most common human helminthiases involve infection with intestinal helminths, such as ascariasis, trichuriasis and hookworms, followed by schistosomiasis. There is an urgent need to develop new measures to control helminth infections, such as vaccinations [6,7,8]. We have previously demonstrated that the catalytic region of the enzyme serine/threonine phosphatase 2A (PP2A), which is highly conserved among a large number of nematode species [9], is capable of inducing partial levels of protection against infections by diverse parasitic nematodes when administered by the mucosal route, intranasally, in mice and lambs

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Results

Conclusion