Beta-propiolactone inactivated bivalent bluetongue virus vaccine containing Montanide ISA-71VG adjuvant induces long-term immune response in sheep against serotypes 4 and 16 even after 3 years of controlled vaccine storage

Zhugunissov, Kuandyk; Bulatov, Yerbol; Taranov, Dmitriy; Yershebulov, Zakir; Koshemetov, Zhumagali K.; Zhunushov, Asankadyr; Renukaradhya, Gourapura J.; Tabynov, Kaissar; Abduraimov, Yergali

doi:10.1016/j.vetmic.2018.10.003

Cited by 4 publications

(4 citation statements)

References 21 publications

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“…Recombinant rDn-ACP encoded by Allele 1 and rDn-MIP encoded by Allele 1 in serotype B strain VPI 2340 [11342] were used in mouse immunisation experiments, using a variety of adjuvant and delivery vehicles that have been shown to enhance the production of antibodies to recombinant proteins: (i) adsorption on Al(OH) 3 was used as standard, as it is a licensed adjuvant routinely used in veterinary vaccines; (ii) mixing with the saponin Quil A has been used successfully for veterinary applications, including in sheep 36 ; (iii) incorporation into liposomes, which provide an intrinsic adjuvant effect and can permit folding of membrane proteins, and are extensively used as a non-toxic delivery vehicle for veterinary vaccine antigens and therapeutic molecules 37–39 ; (iv) incorporation into liposomes with additional immunomodulator monophosphoryl lipid A (MPLA) 39 to increase antigenicity; (v) solubilisation with the zwitterionic detergent Zwittergent (Zw) 3-14, which provides a micellar structure 40 ; (vi) solubilisation with Zw 3–14 containing MPLA; (vii) emulsifying in Freund’s water-in oil emulsion and in the (viii) oil emulsion MONTANIDE ISA 71 VG, as used in cattle, poultry and sheep 41,42 , which enable slow antigen release, thus stimulating high and long-lasting antibody responses. Controls included immunisation with Footvax®, adjuvant mixtures without antigen and normal mouse serum (NMS).…”

Section: Resultsmentioning

confidence: 99%

Characterization of two putative Dichelobacter nodosus footrot vaccine antigens identifies the first lysozyme inhibitor in the genus

Humbert

Jackson

Orr

et al. 2019

Sci Rep

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The Gram-negative anaerobic bacterium Dichelobacter nodosus (Dn) causes footrot in ruminants, a debilitating and highly contagious disease that results in necrotic hooves and significant economic losses in agriculture. Vaccination with crude whole-cell vaccine mixed with multiple recombinant fimbrial proteins can provide protection during species-specific outbreaks, but subunit vaccines containing broadly cross-protective antigens are desirable. We have investigated two D. nodosus candidate vaccine antigens. Macrophage Infectivity Potentiator Dn-MIP (DNO_0012, DNO_RS00050) and Adhesin Complex Protein Dn-ACP (DNO_0725, DNO_RS06795) are highly conserved amongst ~170 D. nodosus isolates in the https://pubmlst.org/dnodosus/ database. We describe the presence of two homologous ACP domains in Dn-ACP with potent C-type lysozyme inhibitor function, and homology of Dn-MIP to other putative cell-surface and membrane-anchored MIP virulence factors. Immunization of mice with recombinant proteins with a variety of adjuvants induced antibodies that recognised both proteins in D. nodosus . Notably, immunization with fimbrial-whole-cell Footvax vaccine induced anti-Dn-ACP and anti-Dn-MIP antibodies. Although all adjuvants induced high titre antibody responses, only antisera to rDn-ACP-QuilA and rDn-ACP-Al(OH) 3 significantly prevented rDn-ACP protein from inhibiting lysozyme activity in vitro . Therefore, a vaccine incorporating rDn-ACP in particular could contribute to protection by enabling normal innate immune lysozyme function to aid bacterial clearance.

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Section: Resultsmentioning

confidence: 99%

Characterization of two putative Dichelobacter nodosus footrot vaccine antigens identifies the first lysozyme inhibitor in the genus

Humbert

Jackson

Orr

et al. 2019

Sci Rep

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“…The traditional adjuvant ISA206 is a water-oil-water emulsion, which may maintain the native structures of antigen better than water-oil adjuvants (Fuentealba et al 2019;G.F. El-Bagoury1 and Darwish2 2010;Zhugunissov et al 2018).…”

Section: Discussionmentioning

confidence: 99%

Polystyrene nanoparticles induce stronger cellular and more durable humoral immune responses against an inactivated bovine herpesvirus 1 isolate

Liu

Xin

Zhang

et al. 2020

Preprint

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The inactivated bovine herpesvirus type 1(BoHV-1) vaccines are generally safe and suitable for use in dairy and pregnant cattle, but induces weaker cellular immune responses and shorter antibody responses compared with the modified live virus vaccine. In this study, we used polystyrene (PS) nanoparticles (100 nm) as a carrier for purified inactivated broken BoHV-1 to improve cellular and humoral immune responses compared with the traditional inactivated vaccine. Mice were injected intramuscularly with the inactivated complex mixed with ISA206 adjuvant. Transmission electron microscopy showed that the PS nanoparticles displayed broken BoHV-1 on their surfaces. After validation of BoHV-1 and gB gC gD gE tegument proteins, it proved that the BoHV-conjugated PS nanoparticles induced higher-titer and more durable antibody responses. The inactivated BoHV-PS nanoparticle complex elicited neutralizing antibodies (titer ~2 6 ) in 5 weeks post-immunization in mice. The CD4/CD8 ratio was higher in mice immunized with PS nanoparticles compared with other groups. However, this ratio reached its maximum 1 week later than in mice immunized with ISA206+BoHV-1 or BoHV-1. Levels of interleukin (IL)-4, IL-6, and interferon-γ in followed similar patterns. In conclusion, this pilot study demonstrated that PS nanoparticles can adjuvant inactivated BoHV-1 vaccines, enhancing both cell-mediated immune responses and the duration of antibody responses. This study provides the foundation for a new development platform for inactivated vaccines, which can elicit potent cellular and humoral immune responses in animals and humans.The inactivated bovine herpesvirus type 1(BoHV-1) vaccines are generally safe and suitable for use in dairy and pregnant cattle, but induces weaker cellular immune responses and shorter antibody responses compared with the modified live virus vaccine. In this study, we used polystyrene (PS) nanoparticles (100 nm) as a carrier for purified inactivated broken BoHV-1 to improve cellular and humoral immune responses compared with the traditional inactivated vaccine. Mice were injected intramuscularly with the inactivated complex mixed with ISA206 adjuvant. Transmission electron microscopy showed that the PS nanoparticles displayed broken BoHV-1 on their surfaces. After validation of BoHV-1 and gB gC gD gE tegument proteins, it proved that the BoHV-conjugated PS nanoparticles induced higher-titer and more durable antibody responses. The inactivated BoHV-PS nanoparticle complex elicited neutralizing antibodies (titer ~2 6 ) in 5 weeks post-immunization in mice. The CD4/CD8 ratio was higher in mice immunized with PS nanoparticles compared with other groups. However, this ratio reached its maximum 1 week later than in mice immunized with ISA206+BoHV-1 or BoHV-1. Levels of interleukin (IL)-4, IL-6, and interferon-γ in followed similar patterns. In conclusion, this pilot study demonstrated that PS nanoparticles can adjuvant inactivated BoHV-1 vaccines, enhancing both cell-mediated immune responses and the duration of antibody responses. This study provides the foundation for a new development platform for inactivated vaccines, which can elicit potent cellular and humoral immune responses in animals and humans.

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“…After 14 days, a second subcutaneous immunization above the popliteal lymph nodes was carried out with 1mL solution containing a 3:7 ratio of 500μg of the antigen to Montanide adjuvant (ISA-71VG, Seppic, France). The addition of the adjuvant was carried out according to that previously described (Zhugunissov et al 2018). During the observation period (21 days) post-second immunization, serum samples from sheep and goats were taken to detect BTV antibody levels every second day.…”

Section: Methodsmentioning

confidence: 99%

Improved Efficiency of Bluetongue Viral Antigen Isolation for Successful Immunization

2022

Int J Vet Sci

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Bluetongue (BT) is a viral disease transmitted by Culicoides spp. The clinical presentation of BT varies widely among susceptible sheep, and in most cases results in severe illness and death in the infected animals. The mortality among susceptible sheep ranges from 2-30% but can occasionally be as high as 70%. Therefore, we investigated a new method to increase the purified BTV-antigen. BTV viral suspensions were purified using Freon-113 and ultracentrifugation through 40% sucrose. We obtained 94.5-95.8% purification of the BT-16 viral antigen. Sheep and cows were immunized with the isolated BTV antigen obtained from this method to confirm antibody specificity to BTV. The antibody activity measured by enzyme-linked immunosorbent assay (ELISA) from goat serum was 7.0log2 to 13.0log2 (on average 10.8±2.28log2) relative to that of sheep (P<0.05 to P<0.0001). We show here that this method can successfully purify BTV-16 antigen and could be used for large-scale production and other BTV serotypes.

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Beta-propiolactone inactivated bivalent bluetongue virus vaccine containing Montanide ISA-71VG adjuvant induces long-term immune response in sheep against serotypes 4 and 16 even after 3 years of controlled vaccine storage

Cited by 4 publications

References 21 publications

Characterization of two putative Dichelobacter nodosus footrot vaccine antigens identifies the first lysozyme inhibitor in the genus

Characterization of two putative Dichelobacter nodosus footrot vaccine antigens identifies the first lysozyme inhibitor in the genus

Polystyrene nanoparticles induce stronger cellular and more durable humoral immune responses against an inactivated bovine herpesvirus 1 isolate

Improved Efficiency of Bluetongue Viral Antigen Isolation for Successful Immunization

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