Vaccination with chimeric protein induces protection in murine model against ascariasis

Castro, Joseane Camilla de; Almeida, Laila Viana de; Cardoso, Mariana Santos; Oliveira, Fabrício Marcus Silva; Nogueira, Denise Silva; Reis-Cunha, João Luís; Magalhães, Luísa Mourão Dias; Zhan, Bin; Bottazzi, María Elena; Hotez, Peter J.; Bueno, Lilian Lacerda; Bartholomeu, Daniella Castanheira; Fujiwara, Ricardo Toshio

doi:10.1016/j.vaccine.2020.11.046

Cited by 14 publications

(11 citation statements)

References 29 publications

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“…Modern vaccine technologies that lead to the discovery of novel immunogenic antigens may accelerate the development of a human Ascaris vaccine in the near future. Rapid advancement in the fields of transcriptomics and proteomics have provided an algorithmic pipeline to predict in silico the most immunogenic and antigenic B- and T-cell epitopes from Ascaris parasites based on their molecular and structural features (de Castro et al ., 2021). With this technology, it has become possible to screen the entire parasite without the need to maintain the parasite life cycle in vivo .…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

“…Finally, As14, As16 and As37 have recently been used together as a multivalent epitope-based vaccine in pre-clinical trials against Ascaris infection (de Castro et al ., 2021). The most immunogenic epitopes from the three selected proteins were predicted using bioinformatic tools.…”

Section: Promising Recombinant Protein Ascaris Vaccine Targets: As14 As16 and As37mentioning

confidence: 99%

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A historical and systematic overview of Ascaris vaccine development

Gazzinelli-Guimarães¹,

Gazzinelli-Guimarães²

2021

Parasitology

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Ascariasis is the most prevalent helminth infection in the world and leads to significant, life-long morbidity, particularly in young children. Current efforts to control and eradicate ascariasis in endemic regions have been met with significant challenges including high-rates of re-infection and potential development of anthelminthic drug resistance. Vaccines against ascariasis are a key tool that could break the transmission cycle and lead to disease eradication globally. Evolution of the Ascaris vaccine pipeline has progressed, however no vaccine product has been brought to human clinical trials to date. Advancement in recombinant protein technology may provide the first step in generating an Ascaris vaccine as well as a pan-helminthic vaccine ready for human trials. However, several roadblocks remain and investment in new technologies will be important to develop a successful human Ascaris vaccine that is critically needed to prevent significant morbidity in Ascaris-endemic regions around the world.

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Section: Discussion and Future Directionsmentioning

confidence: 99%

Section: Promising Recombinant Protein Ascaris Vaccine Targets: As14 As16 and As37mentioning

confidence: 99%

A historical and systematic overview of Ascaris vaccine development

Gazzinelli-Guimarães¹,

Gazzinelli-Guimarães²

2021

Parasitology

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“…The combination of these protective antigens as a multivalent vaccine could be a strategy to enhance protective immunity. Based on this approach, de Castro et al (15) recently constructed a chimeric antigen based on the B-cell epitopes from protective antigens As37, As16, and As14 (15). Notably, mice immunized with this new chimeric protein alone (without adjuvant) showed a 42.9% reduction in larval burden compared to the control group after challenge with Ascaris eggs (15).…”

Section: Discussionmentioning

confidence: 99%

“…Through a literature search, we identified several protective antigens from A. suum, a parasite that infects both humans and pigs and shows 99% genetic similarity with the human A. lumbricoides parasite (6). These antigens include As14 (7), As16 (8,9), As24 (10), As37 (11,12), enolase-1 (13), AsPPase (14), and BOT (15), which have been expressed as recombinant proteins in different expression systems and used in preclinical trials. As described in a recent study (16), immunization with crude extract of adult A. suum worms (ExAD), crude extract of adult worm cuticles (CUT), and crude extract of infective larvae (L3) (ExL3) provoked a B-cell specific response in BALB/c mice, leading to high levels of IgG and a 60% worm reduction (16).…”

Section: Introductionmentioning

confidence: 99%

ASCVac-1, a Multi-Peptide Chimeric Vaccine, Protects Mice Against Ascaris suum Infection

et al. 2021

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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.

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“…Promising recombinant Ascaris antigens such as As14, As16 and As37 (Tsuji et al ., 2001, 2002) have been identified and a recent study by de Castro et al . (2021) outlines the use of a more intricate vaccine target, an adjuvanted chimeric protein derived from the three recombinants with an efficacy of 73.54% in BALB/c mice. Our continued paucity of knowledge of the totality of the Ascaris immune responses and the possibility that other undiscovered proteins may exist and act as better vaccine targets remains an ongoing challenge.…”

Section: Vaccine Developmentmentioning

confidence: 99%

Lessons from studying roundworm and whipworm in the mouse: common themes and unique features

Holland

Else

2021

Parasitology

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Ascaris lumbricoides, the roundworm, and Trichuris trichiura, the whipworm, are human intestinal nematode parasites; both are soil-transmitted helminths, are often placed together in an epidemiological context and both remain neglected despite high prevalence. Our understanding of parasitic disease continues to be enhanced through animal models. Despite the similarities between whipworm and roundworm, there are key differences between the two species and these have influenced the application of their respective animal models. In the case of T. trichiura, the fact that a murine equivalent, T. muris completes its life cycle in a mouse model has greatly enhanced our knowledge of whipworm biology, pathogenicity and immunology. In contrast, A. lumbricoides and its porcine equivalent, Ascaris suum, lack a rodent model in which the life cycle is completed. However, evidence continues to accumulate demonstrating that mice represent useful models of early Ascaris infection, a key stage of the life cycle. The use of mouse models for both Ascaris and Trichuris has a long history with early pioneers discovering fundamental aspects of each parasite's biology. Novel technologies and perspectives, as outlined in this special issue, demonstrate how through the prism of mouse models, we can continue to explore the similarities and differences between roundworms and whipworms.

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Vaccination with chimeric protein induces protection in murine model against ascariasis

Cited by 14 publications

References 29 publications

A historical and systematic overview of Ascaris vaccine development

A historical and systematic overview of Ascaris vaccine development

ASCVac-1, a Multi-Peptide Chimeric Vaccine, Protects Mice Against Ascaris suum Infection

Lessons from studying roundworm and whipworm in the mouse: common themes and unique features

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