Biophysical and formulation studies of the<i>Schistosoma mansoni</i>TSP-2 extracellular domain recombinant protein, a lead vaccine candidate antigen for intestinal schistosomiasis

Cheng, Weiqiang; Curti, Elena; Rezende, Wanderson; Kwityn, Clifford; Zhan, Bin; Gillespie, Portia M.; Plieskatt, Jordan; Joshi, Sangeeta B.; Volkin, David B.; Hotez, Peter J.; Middaugh, C. Russell; Bottazzi, María Elena

doi:10.4161/hv.25788

Cited by 19 publications

(7 citation statements)

References 39 publications

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“…However, compared to each adjuvant alone control, only As37 formulated with AddaVax induced significant protection (48.7%, P<0.01). Alhydrogel is an alum-based adjuvant mainly stimulating a Th2-type response [48,49], confirmed by the high ratio of IgG1/IgG2a (380:1) and high levels of IL-4, IL-5, and IL-10 in this study. MPLA (Monophosphoryl Lipid A) is a potent activator of TLR4 that stimulates a strong Th1 response or a combined Th1/Th2 response [50], confirmed by high levels of INF-γ and a low IgG1/IgG2a ratio (20:1).…”

Section: Discussionsupporting

confidence: 72%

Protective immunity elicited by the nematode-conserved As37 recombinant protein against Ascaris suum infection

et al. 2020

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Background Ascaris lumbricoides is one of the three major soil-transmitted gastrointestinal helminths (STHs) that infect more than 440 million people in the world, ranking this neglected tropical disease among the most common afflictions of people living in poverty. Children infected with this roundworm suffer from malnutrition, growth stunting as well as cognitive and intellectual deficits. An effective vaccine is urgently needed to complement anthelmintic deworming as a better approach to control helminth infections. As37 is an immunodominant antigen of Ascaris suum, a pig roundworm closely related to the human A. lumbricoides parasite, recognized by protective immune sera from A. suum infected mice. In this study, the immunogenicity and vaccine efficacy of recombinant As37 were evaluated in a mouse model.

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Section: Discussionsupporting

confidence: 72%

Protective immunity elicited by the nematode-conserved As37 recombinant protein against Ascaris suum infection

et al. 2020

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“…To further interpret the protective immunological mechanism underlying the protection induced by As16, three other adjuvants (Alhydrogel, MPLA and AddaVax) were formulated with rAs16. Alhydrogel, an alum-based adjuvant approved by the FDA for use in humans, is known to stimulate a Th2-type response [ 50 , 51 ]. MPLA (Monophosphoryl Lipid A) is a potent activator of TLR4 that boosts a combined Th1/Th2 response [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Yeast-expressed recombinant As16 protects mice against Ascaris suum infection through induction of a Th2-skewed immune response

et al. 2017

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BackgroundAscariasis remains the most common helminth infection in humans. As an alternative or complementary approach to global deworming, a pan-anthelminthic vaccine is under development targeting Ascaris, hookworm, and Trichuris infections. As16 and As14 have previously been described as two genetically related proteins from Ascaris suum that induced protective immunity in mice when formulated with cholera toxin B subunit (CTB) as an adjuvant, but the exact protective mechanism was not well understood.Methodology/Principal findingsAs16 and As14 were highly expressed as soluble recombinant proteins (rAs16 and rAs14) in Pichia pastoris. The yeast-expressed rAs16 was highly recognized by immune sera from mice infected with A. suum eggs and elicited 99.6% protection against A. suum re-infection. Mice immunized with rAs16 formulated with ISA720 displayed significant larva reduction (36.7%) and stunted larval development against A. suum eggs challenge. The protective immunity was associated with a predominant Th2-type response characterized by high titers of serological IgG1 (IgG1/IgG2a > 2000) and high levels of IL-4 and IL-5 produced by restimulated splenocytes. A similar level of protection was observed in mice immunized with rAs16 formulated with alum (Alhydrogel), known to induce mainly a Th2-type immune response, whereas mice immunized with rAs16 formulated with MPLA or AddaVax, both known to induce a Th1-type biased response, were not significantly protected against A. suum infection. The rAs14 protein was not recognized by A. suum infected mouse sera and mice immunized with rAs14 formulated with ISA720 did not show significant protection against challenge infection, possibly due to the protein’s inaccessibility to the host immune system or a Th1-type response was induced which would counter a protective Th2-type response.Conclusions/SignificanceYeast-expressed rAs16 formulated with ISA720 or alum induced significant protection in mice against A. suum egg challenge that associates with a Th2-skewed immune response, suggesting that rAS16 could be a feasible vaccine candidate against ascariasis.

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“…In both Bm- FAR-1 and Bm- FAR-2 immunization, Montanide-720 adjuvant induced better protection than did alum. Montanide-720 is a water-in-oil emulsion preparation that induces strong and broad Th1- and Th2-associated humoral and cellular immune responses [ 46 , 47 ], while alum is known to stimulate a Th2-type humoral and cellular response [ 48 ]. The adjuvants used here may therefore elicit different immunoglobulin isotype dominances (e.g.…”

Section: Discussionmentioning

confidence: 99%

Ligand binding properties of two Brugia malayi fatty acid and retinol (FAR) binding proteins and their vaccine efficacies against challenge infection in gerbils

et al. 2018

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Parasitic nematodes produce an unusual class of fatty acid and retinol (FAR)-binding proteins that may scavenge host fatty acids and retinoids. Two FARs from Brugia malayi (Bm-FAR-1 and Bm-FAR-2) were expressed as recombinant proteins, and their ligand binding, structural characteristics, and immunogenicities examined. Circular dichroism showed that rBm-FAR-1 and rBm-FAR-2 are similarly rich in α-helix structure. Unexpectedly, however, their lipid binding activities were found to be readily differentiated. Both FARs bound retinol and cis-parinaric acid similarly, but, while rBm-FAR-1 induced a dramatic increase in fluorescence emission and blue shift in peak emission by the fluorophore-tagged fatty acid (dansyl-undecanoic acid), rBm-FAR-2 did not. Recombinant forms of the related proteins from Onchocerca volvulus, rOv-FAR-1 and rOv-FAR-2, were found to be similarly distinguishable. This is the first FAR-2 protein from parasitic nematodes that is being characterized. The relative protein abundance of Bm-FAR-1 was higher than Bm-FAR-2 in the lysates of different developmental stages of B. malayi. Both FAR proteins were targets of strong IgG1, IgG3 and IgE antibody in infected individuals and individuals who were classified as endemic normal or putatively immune. In a B. malayi infection model in gerbils, immunization with rBm-FAR-1 and rBm-FAR-2 formulated in a water-in-oil-emulsion (®Montanide-720) or alum elicited high titers of antigen-specific IgG, but only gerbils immunized with rBm-FAR-1 formulated with the former produced a statistically significant reduction in adult worms (68%) following challenge with B. malayi infective larvae. These results suggest that FAR proteins may play important roles in the survival of filarial nematodes in the host, and represent potential candidates for vaccine development against lymphatic filariasis and related filarial infections.

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Biophysical and formulation studies of theSchistosoma mansoniTSP-2 extracellular domain recombinant protein, a lead vaccine candidate antigen for intestinal schistosomiasis

Cited by 19 publications

References 39 publications

Protective immunity elicited by the nematode-conserved As37 recombinant protein against Ascaris suum infection

Protective immunity elicited by the nematode-conserved As37 recombinant protein against Ascaris suum infection

Yeast-expressed recombinant As16 protects mice against Ascaris suum infection through induction of a Th2-skewed immune response

Ligand binding properties of two Brugia malayi fatty acid and retinol (FAR) binding proteins and their vaccine efficacies against challenge infection in gerbils

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