Abstract
Control of human ascariasis, the most prevalent neglected tropical disease globally affecting 450 million people, mostly relies on mass drug administration of anthelmintics. However, chemotherapy alone is not efficient due to the high re-infection rate for people who live in the endemic area. The development of a vaccine that reduces the intensity of infection and maintains lower morbidity should be the primary target for infection control. Previously, our group demonstrated that immunization with crude Ascaris antigens in mice induced an IgG-mediated protective response with significant worm reduction. Here, we aimed to develop a multipeptide chimera vaccine based on conserved B-cell epitopes predicted from 17 common helminth proteomes using a bioinformatics algorithm. More than 480 B-cell epitopes were identified that are conserved in all 17 helminths. The Ascaris-specific epitopes were selected based on their reactivity to the pooled sera of mice immunized with Ascaris crude antigens or infected three times with A. suum infective eggs. The top 35 peptides with the strongest reactivity to Ascaris immune serum were selected to construct a chimeric antigen connected in sequence based on conformation. This chimera, called ASCVac-1, was produced as a soluble recombinant protein in an Escherichia coli expression system and, formulated with MPLA, was used to immunize mice. Mice immunized with ASCVac-1/MPLA showed around 50% reduced larvae production in the lungs after being challenged with A. suum infective eggs, along with significantly reduced inflammation and lung tissue/function damage. The reduced parasite count and pathology in infected lungs were associated with strong Th2 immune responses characterized by the high titers of antigen-specific IgG and its subclasses (IgG1, IgG2a, and IgG3) in the sera and significantly increased IL-4, IL-5, IL-13 levels in lung tissues. The reduced IL-33 titers and stimulated eosinophils were also observed in lung tissues and may also contribute to the ASCVac-1-induced protection. Taken together, the preclinical trial with ASCVac-1 chimera in a mouse model demonstrated its significant vaccine efficacy associated with strong IgG-based Th2 responses, without IgE induction, thus reducing the risk of an allergic response. All results suggest that the multiepitope-based ASCVac-1 chimera is a promising vaccine candidate against Ascaris sp. infections.
Highlights
Human ascariasis is one of the most common intestinal parasitic diseases in developing countries
The current strategy for human ascariasis control is predominantly based on mass drug administration (MDA) with a benzimidazole class of anthelmintics that are effective in removing active helminth infections
The development of a vaccine that provides long-term protection against Ascaris or at least reduces the parasite burden to lower morbidity in the population living in endemic areas should be considered as the main control strategy for Ascaris infection
Summary
Human ascariasis is one of the most common intestinal parasitic diseases in developing countries. Recent studies estimate that approximately 450 million people are infected worldwide [1], and this high prevalence is strongly associated with poverty and precarious health conditions, mainly in tropical and subtropical areas of sub‐Saharan Africa, Southeast Asia, and South America [2,3,4]. There is still no vaccine available for Ascaris, and mass drug administration is currently the main form of infection control in humans and pigs, one of the most important animal hosts. To improve the quality of life, reducing morbidity in endemic areas, the development of a vaccine that reduces the intensity of infection or provides long-term protection should be the primary goal of parasite control. The use of new technologies, such as the production of recombinant proteins, the construction of synthetic genes, and multivalent, chimeric vaccines consisting of several antigens, will facilitate the characterization of proteins and allow the production of large amounts and varieties of antigens in the laboratory and beyond
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