Equine Immunoglobulin and Equine Neutralizing F(ab′)2 Protect Mice from West Nile Virus Infection

Wang, Cuiling; Zhao, Yongkun; Wang, Hualei; Qiu, Boning; Cao, Zongjie; Li, Qian; Zhang, Yanbo; Yan, Feihu; Jin, Hongli; Wang, Tiecheng; Sun, Wenzhao; Feng, Na; Gao, Yuwei; Sun, Jing; Wang, Yanqun; Perlman, Stanley; Zhao, Jincun; Xia, Xianzhu

doi:10.3390/v8120332

Cited by 6 publications

(4 citation statements)

References 30 publications

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“…In addition, the expression of HSP70, one of the most important cellular defense mechanisms, is induced under stressful conditions such as infection 54 . Interestingly, HSP70, GSH-Px and total antioxidant capacity are significantly up-regulated in pigs and rats after PEDV infection 55 – 57 . A study found that Nrf2 may increase the expression of antioxidant related genes by acting on the antioxidant response element (ARE) in the gene promoter, therefore control abnormal oxidative stress 58 .…”

Section: Discussionmentioning

confidence: 98%

Puerarin enhances intestinal function in piglets infected with porcine epidemic diarrhea virus

Zhang

et al. 2021

Sci Rep

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Puerarin has been reported to be an excellent antioxidant, anti-inflammatory and antimicrobial agent, but the potential effect of puerarin on porcine epidemic diarrhea virus (PEDV) is unclear. This study aimed to determine whether puerarin could alleviate intestinal injury in piglets infected with PEDV. A PEDV (Yunnan province strain) infection model was applied to 7-day-old piglets at 104.5 TCID50 (50% tissue culture infectious dose). Piglets were orally administered with puerarin at the dosage of 0.5 mg/kg body weight from day 5 to day 9. On day 9 of the trial, piglets were inoculated orally with PEDV. Three days later, jugular vein blood and intestinal samples were collected. Results showed puerarin reduced morbidity of piglets infected with PEDV. In addition, puerarin reduced the activities of aspartate aminotransferase and alkaline phosphatase, the ratio of serum aspartate aminotransferase to serum alanine aminotransferase, the number of white blood cells and neutrophils, and the plasma concentrations of interleukin-6, interleukin-8 and tumor necrosis factor-α, as well as protein abundances of heat shock protein-70 in PEDV-infected piglets. Moreover, puerarin increased D-xylose concentration but decreased intestinal fatty acid-binding protein concentration and diamine oxidase activity in the plasma of piglets infected with PEDV. Puerarin increased the activities of total superoxide dismutase, glutathione peroxidase and catalase, while decreasing the activities of myeloperoxidase and concentration of hydrogen peroxide in both the intestine and plasma of PEDV-infected piglets. Puerarin decreased mRNA levels of glutathione S-transferase omega 2 but increased the levels of nuclear factor erythroid 2-related factor 2. Furthermore, puerarin increased the abundance of total eubacteria (16S rRNA), Enterococcus genus, Lactobacillus genus and Enterobacteriaceae family in the intestine, but reduced the abundance of Clostridium coccoides in the caecum. These data indicate puerarin improved intestinal function in piglets infected by PEDV and may be a promising supplement for the prevention of PEDV infection.

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Section: Discussionmentioning

confidence: 98%

Puerarin enhances intestinal function in piglets infected with porcine epidemic diarrhea virus

Zhang

et al. 2021

Sci Rep

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“…In support of such a mechanism of action, Ide‐cleaved specific anti‐streptococcal Abs were shown to maintain protective binding activity 23 and, albeit to a variable degree, also F(ab’) 2 fragments specific for other pathogens/toxins can retain their binding capacity. 24 , 25 , 26 , 27 However, for other serotypes like AAV8, only a mild and transient inhibition on liver transduction by IdeS‐cleavage products was observed at the NAb titre tested. Interestingly, in vitro data for the two serotypes revealed that the cleavage products have similar capacity to inhibit transduction.…”

Section: Discussionmentioning

confidence: 98%

Optimising the IgG‐degrading enzyme treatment regimen for enhanced adeno‐associated virus transduction in the presence of neutralising antibodies

Ros‐Gañán¹,

Hommel

Trigueros-Motos³

et al. 2022

Clin & Trans Imm

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Objective Pre‐existing neutralising antibodies (NAbs) to adeno‐associated viruses (AAVs) remain an impediment for systemically administered AAV‐mediated gene therapy treatment in many patients, and various strategies are under investigation to overcome this limitation. Here, IgG‐degrading enzymes (Ides) derived from bacteria of the genus Streptococcus were tested for their ability to cleave human IgG and allow AAV‐mediated transduction in individuals with pre‐existing NAbs. Methods Cleavage activity of three different Ides was evaluated in vitro in serum from different species. Passively immunised mice or non‐human primates (NHP) with naturally occurring anti‐AAV NAbs were used to define the optimal IdeS dose and administration window for AAVAnc80 and AAV8 vectors in mice and AAV3B in NHPs. Results The selected candidate, IdeS, was found to be highly efficient at cleaving human IgG, less efficient against NHP IgG and inefficient against mouse IgG. In vivo , we observed differences in how IdeS affected liver transduction in the presence of NAbs depending on the AAV serotype. For AAVAnc80 and AAV3B, the best transduction levels were achieved when the vector was administered after IgG digestion products were cleared from circulation. However, for AAV8 we only observed a modest and transient inhibition of transduction by IdeS cleavage products. Conclusion Preconditioning with IdeS represents a unique treatment opportunity for patients primarily excluded from participation in gene therapy clinical trials because of elevated circulating anti‐AAV NAb levels. However, careful determination of the optimal IdeS dose and timing for the administration of each AAV serotype is essential for optimal transduction.

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“…F(ab′) 2 fragments, being bivalent, are easier to purify in large quantities and more able to penetrate deeper into the tissue than the IgG antibody [6], thus increasing the time for excretion from the blood. There are reports on using F(ab′) 2 fragments to prevent West Nile virus (WNV) [7], feline calicivirus [8], Middle East respiratory syndrome coronavirus (MERS-CoV) [9] and Ebola virus (EBOV) [10,11].…”

Section: Introductionmentioning

confidence: 99%

Prophylactic Efficacy of Equine Immunoglobulin F(ab′)2 Fragments Against Feline Parvovirus

Liu

Zhang

Bai

et al. 2021

Appl Biochem Biotechnol

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Feline parvovirus (FPV), a type of parvovirus prevalent worldwide, can cause foetal death and acute enteritis in adult cats with severe leukopenia, and yet there are no effective drugs to prevent or treat FPV. Here, the immune effects of two FPV vaccines on horses were compared. IgG was extracted from FPV-immunized horse sera. Equine F(ab′) 2 fragments were obtained from pepsin-digested IgG and then purified by protein-G column chromatography. The results showed that the inactivated FPV oil vaccine was more effective than the inactivated FPV propolis vaccine in helping healthy horses to produce hyper-immune serum. Four methods were tested, among which the optimized octanoic acid-ammonium sulphate precipitation method was proved to be the best process for extracting IgG. The optimal condition for preparing F(ab′) 2 by pepsin digestion was 30°C for 3.5 h, and the content, purity and recovery of F(ab′) 2 were 8.64 mg/mL, 90.36% and 93.24%, respectively. Our equine immunoglobulin F(ab′) 2 fragments effectively neutralized activity in vitro against FPV, alleviated the clinical symptoms of FPVinfected cats, reduced the viral loads in the intestine and had prophylactic effects in FPV-infected cats. These results indicate that the F(ab′) 2 fragment prepared from inactivated FPV-immunized horses may be used as a prophylactic agent for diseases caused by FPV.

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Equine Immunoglobulin and Equine Neutralizing F(ab′)2 Protect Mice from West Nile Virus Infection

Cited by 6 publications

References 30 publications

Puerarin enhances intestinal function in piglets infected with porcine epidemic diarrhea virus

Puerarin enhances intestinal function in piglets infected with porcine epidemic diarrhea virus

Optimising the IgG‐degrading enzyme treatment regimen for enhanced adeno‐associated virus transduction in the presence of neutralising antibodies

Prophylactic Efficacy of Equine Immunoglobulin F(ab′)2 Fragments Against Feline Parvovirus

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