Immunization of Goats with Recombinant Protein 14-3-3 Isoform 2(rHcftt-2) Induced Moderate Protection against Haemonchus contortus Challenge

Bu, Youngmin; Jia, Caiwen; Tian, Xiaowei; Aimulajiang, Kalibixiati; Memon, Muhammad Ali; Ren, Yan; Song, Xiaoling; Xu, Lixin; Li, Xiangrui

doi:10.3390/pathogens9010046

Cited by 12 publications

(11 citation statements)

References 42 publications

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“…The EPG reduction rate was calculated by: (average EPG in control -average EPG in treatment)/average EPG in control ϫ 100%. The numbers of H. contortus adult worms from the abomasum in sheep were counted as described previously (40,41) after euthanasia at week 11. The worm reduction rate was calculated as follows: (average worm count in control -average worm count in treatment)/average worm count in control ϫ 100%.…”

Section: Methodsmentioning

confidence: 99%

Recombinant HcGAPDH Protein Expressed on Probiotic Bacillus subtilis Spores Protects Sheep from Haemonchus contortus Infection by Inducing both Humoral and Cell-Mediated Responses

Yang

Zhang

et al. 2020

mSystems

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Probiotic Bacillales are effective in controlling pathogens. Live probiotic bacteria improve the composition of the gastrointestinal microbiota, leading to a reduction in pathogen colonization. However, it remains largely unknown how probiotics regulate the host’s immunologic responses and protect the host from parasitic infection. In this study, we addressed whether Bacillales were effective against Haemonchus contortus, a parasitic nematode that infects small ruminants worldwide. Using 16S rRNA sequencing, we found that Bacillales were largely depleted in the abomasal microbiota of sheep infected with H. contortus. We constructed a recombinant Bacillus subtilis named rBSCotB-HcG that express the glyceraldehyde-3-phosphate dehydrogenase of H. contortus (HcGAPDH) on its spore surface using the Bacillus subtilis spore coat protein B (CotB) as a carrier. Mice receiving rBSCotB-HcG orally showed strong Th1-dominated immune responses. More importantly, sheep administered BSCotB-HcG per os showed increasing proliferation of the peripheral blood mononucleates, elevated anti-HcGAPDH IgG in sera, and higher anti-HcGAPDH sIgA in the intestinal mucus than the control sheep. The average weight gain of H. contortus-infected sheep treated with rBSCotB-HcG (Hc+rBSCotB-HcG) was 48.73% greater than that of unvaccinated sheep. Furthermore, these Hc+rBSCotB-HcG sheep had fewer eggs per gram of feces by 84.1% and adult worms by 71.5%. They also demonstrated greatly lessened abomasal damage by H. contortus with an abundance of probiotic species in the abomasal microbiota. Collectively, our data unequivocally demonstrate the protective roles of CotB-HcGAPDH-expressing B. subtilis spores in against H. contortus infection and showed great potential of using probiotic-based strategy in controlling parasitic nematodes of socioeconomic importance in general. IMPORTANCE Initial analyses of the abomasal microbiota of sheep using 16S rRNA sequencing suggested that probiotic bacteria played a protective role in against H. contortus infection. A recombinant Bacillus subtilis expressing a fusion protein CotB-HcGAPDH on its spore’s surface induced strong Th1 immune response in a murine model. The same probiotic recombinant, upon only one oral application, protected sheep against H. contortus infection by reducing egg shedding and decreasing adult worm loads of the parasite and increasing body weight gain of infected sheep. Both Th1 and Th2 immune responses were evident in these immunized sheep.

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Section: Methodsmentioning

confidence: 99%

Recombinant HcGAPDH Protein Expressed on Probiotic Bacillus subtilis Spores Protects Sheep from Haemonchus contortus Infection by Inducing both Humoral and Cell-Mediated Responses

Yang

Zhang

et al. 2020

mSystems

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“…In addition, some studies based on H. contortus gut membrane antigen as a molecular vaccine showed a significant reduction in FECs by >90% and AWB by 72–80% in vivo [ 71 , 72 ]. Recently, Bu and colleagues have proven that another vaccine target antigen (rHcftt-2) identified previously as a vital-interacting protein to host peripheral blood mononuclear cells (PBMCs) reduced FECs and AWB by 26.46% and 32.33%, respectively [ 73 ]. Therefore, these studies have provided directions for the search of potential ES molecules with the best protective efficiency for the development of an effective vaccine in the near future.…”

Section: Historical Account Of H Contortus Vacmentioning

confidence: 99%

Advances in the Development of Anti-Haemonchus contortus Vaccines: Challenges, Opportunities, and Perspectives

Ehsan

Liang

et al. 2020

Vaccines

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The gastrointestinal nematode parasite Haemonchus contortus (H. contortus) is a resident of tropical and subtropical regions worldwide that imposes significant production losses, economic losses, and animal health issues in the small ruminant industry, particularly sheep and goats. Considerable efforts have been made to understand how immunity is elicited against H. contortus infection. Various potential vaccine antigens have been tested by different methods and strategies applied in animal models, and significant progress has been made in the development of vaccines against H. contortus. This review highlighted and shared the knowledge about the current understanding of host immune responses to H. contortus and ongoing challenges in the development of a protective, effective, and long-lasting vaccine against H. contortus infection. We have also pinpointed some achievements and failures in the development and testing of vaccines, which will establish a road map for future research directions to explore new effective vaccine candidates for controlling and preventing H. contortus infection.

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“…For H. contortus , a variety of native ES proteins including AC-5 [ 12 ], thiol-binding proteins [ 13 ], LDNF glycan antigen [ 14 ], and 15- and 24-kDa ES proteins [ 15 ] offered partial immune-protective effects to different sheep breeds at varying ages when co-administered with corresponding adjuvants. Simultaneously, a number of the recombinant versions of ES proteins also delivered notable levels of protection against H. contortus challenge, such as recombinant HcENO protein [ 16 ], recombinant Hcftt-2 protein [ 17 ], and recombinant 15- and 24-kDa ES proteins [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Protection studies of an excretory–secretory protein HcABHD against Haemonchus contortus infection

Tian

Zhang

et al. 2021

Vet Res

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Unlike the successful immunization of native H. contortus antigens that contributed to the realization of the first commercial vaccine Barbervax, not many studies revealed the encouraging protective efficacies of recombinant H. contortus antigens in laboratory trials or under field conditions. In our preliminary study, H. contortus α/β-hydrolase domain protein (HcABHD) was demonstrated to be an immunomodulatory excretory–secretory (ES) protein that interacts with goat T cells. We herein evaluated the protective capacities of two HcABHD preparations, recombinant HcABHD (rHcABHD) antigen and anti-rHcABHD IgG, against H. contortus challenge via active and passive immunization trials, respectively. Parasitological parameter, antibody responses, hematological pathology and cytokine profiling in unchallenged and challenged goats were monitored and determined throughout both trials. Subcutaneous administration of rHcABHD with Freund adjuvants elicited protective immune responses in challenged goats, diminishing cumulative fecal egg counts (FEC) and total worm burden by 54.0% and 74.2%, respectively, whereas passive immunization with anti-rHcABHD IgG conferred substantial protection to challenged goats by generating a 51.5% reduction of cumulative FEC and a 73.8% reduction of total worm burden. Additionally, comparable changes of mucosal IgA levels, circulating IgG levels, hemoglobin levels, and serum interleukin (IL)-4 and IL-17A levels were observed in rHcABHD protein/anti-rHcABHD IgG immunized goats in both trials. Taken together, the recombinant version of HcABHD might have further application under field conditions in protecting goats against H. contortus infection, and the integrated immunological pipeline of ES antigen identification, screening and characterization may provide new clues for further development of recombinant subunit vaccines to control H. contortus.

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Immunization of Goats with Recombinant Protein 14-3-3 Isoform 2(rHcftt-2) Induced Moderate Protection against Haemonchus contortus Challenge

Cited by 12 publications

References 42 publications

Recombinant HcGAPDH Protein Expressed on Probiotic Bacillus subtilis Spores Protects Sheep from Haemonchus contortus Infection by Inducing both Humoral and Cell-Mediated Responses

Recombinant HcGAPDH Protein Expressed on Probiotic Bacillus subtilis Spores Protects Sheep from Haemonchus contortus Infection by Inducing both Humoral and Cell-Mediated Responses

Advances in the Development of Anti-Haemonchus contortus Vaccines: Challenges, Opportunities, and Perspectives

Protection studies of an excretory–secretory protein HcABHD against Haemonchus contortus infection

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