Viral Dose and Immunosuppression Modulate the Progression of Acute BVDV-1 Infection in Calves: Evidence of Long Term Persistence after Intra-Nasal Infection
Abstract:Bovine viral diarrhoea virus (BVDV) infection of cattle causes a diverse range of clinical outcomes from being asymptomatic, or a transient mild disease, to producing severe cases of acute disease leading to death. Four groups of calves were challenged with a type 1 BVDV strain, originating from a severe outbreak of BVDV in England, to study the effect of viral dose and immunosuppression on the viral replication and transmission of BVDV. Three groups received increasing amounts of virus: Group A received 102.5… Show more
“…Interestingly, all groups showed a second peak in viral RNA, which was particularly apparent in the Vaccine-NP and IAV group, where the two groups show the same trend albeit offset. Viral RNA was cleared from the blood of the Vaccine-NP and IAV groups on day 21 and 18, respectively, whereas, viral RNA was still detectable in the blood of Control-NP animals at the termination of the experiment (day 24 post-challenge), which is in line with another observation the more pathogenic strains such as Ho916 induce a persistent infection in post-natal infection 32 . Figure 5 Detection of BVDV in the blood of vaccinated animals following challenge infection.…”
Section: Resultssupporting
confidence: 85%
“…On 41 dpv, all cattle received an intranasal inoculation with 5 × 10 6 TCID 50 BVDV-1a Ho916 in 2 ml BT medium, which was confirmed by back titration. Clinical scores and rectal temperatures were monitored prior to viral challenge and on a daily basis subsequently 32 . Blood samples were collected longitudinally over the course of vaccination and challenge to assess serum antibody and peripheral blood T cell IFN-γ responses, and to monitor for viral loads.…”
Subunit viral vaccines are typically not as efficient as live attenuated or inactivated vaccines at inducing protective immune responses. This paper describes an alternative ‘biomimetic’ technology; whereby viral antigens were formulated around a polymeric shell in a rationally arranged fashion with a surface glycoprotein coated on to the surface and non-structural antigen and adjuvant encapsulated. We evaluated this model using BVDV E2 and NS3 proteins formulated in poly-(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles adjuvanted with polyinosinic:polycytidylic acid (poly(I:C) as an adjuvant (Vaccine-NP). This Vaccine-NP was compared to ovalbumin and poly(I:C) formulated in a similar manner (Control-NP) and a commercial adjuvanted inactivated BVDV vaccine (IAV), all inoculated subcutaneously and boosted prior to BVDV-1 challenge. Significant virus-neutralizing activity, and E2 and NS3 specific antibodies were observed in both Vaccine-NP and IAV groups following the booster immunisation. IFN-γ responses were observed in ex vivo PBMC stimulated with E2 and NS3 proteins in both vaccinated groups. We observed that the protection afforded by the particulate vaccine was comparable to the licenced IAV formulation. In conclusion, the biomimetic particulates showed a promising immunogenicity and efficacy profile that may be improved by virtue of being a customisable mode of delivery.
“…Interestingly, all groups showed a second peak in viral RNA, which was particularly apparent in the Vaccine-NP and IAV group, where the two groups show the same trend albeit offset. Viral RNA was cleared from the blood of the Vaccine-NP and IAV groups on day 21 and 18, respectively, whereas, viral RNA was still detectable in the blood of Control-NP animals at the termination of the experiment (day 24 post-challenge), which is in line with another observation the more pathogenic strains such as Ho916 induce a persistent infection in post-natal infection 32 . Figure 5 Detection of BVDV in the blood of vaccinated animals following challenge infection.…”
Section: Resultssupporting
confidence: 85%
“…On 41 dpv, all cattle received an intranasal inoculation with 5 × 10 6 TCID 50 BVDV-1a Ho916 in 2 ml BT medium, which was confirmed by back titration. Clinical scores and rectal temperatures were monitored prior to viral challenge and on a daily basis subsequently 32 . Blood samples were collected longitudinally over the course of vaccination and challenge to assess serum antibody and peripheral blood T cell IFN-γ responses, and to monitor for viral loads.…”
Subunit viral vaccines are typically not as efficient as live attenuated or inactivated vaccines at inducing protective immune responses. This paper describes an alternative ‘biomimetic’ technology; whereby viral antigens were formulated around a polymeric shell in a rationally arranged fashion with a surface glycoprotein coated on to the surface and non-structural antigen and adjuvant encapsulated. We evaluated this model using BVDV E2 and NS3 proteins formulated in poly-(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles adjuvanted with polyinosinic:polycytidylic acid (poly(I:C) as an adjuvant (Vaccine-NP). This Vaccine-NP was compared to ovalbumin and poly(I:C) formulated in a similar manner (Control-NP) and a commercial adjuvanted inactivated BVDV vaccine (IAV), all inoculated subcutaneously and boosted prior to BVDV-1 challenge. Significant virus-neutralizing activity, and E2 and NS3 specific antibodies were observed in both Vaccine-NP and IAV groups following the booster immunisation. IFN-γ responses were observed in ex vivo PBMC stimulated with E2 and NS3 proteins in both vaccinated groups. We observed that the protection afforded by the particulate vaccine was comparable to the licenced IAV formulation. In conclusion, the biomimetic particulates showed a promising immunogenicity and efficacy profile that may be improved by virtue of being a customisable mode of delivery.
“…Despite the short duration for viral excretion in TI animals, it has been reported that it may be sufficient at sustaining infection within a herd in the absence of a PI animal (Collins, Heaney, Thomas, & Brownlie, 2009;Moen et al, 2005) although other experimental studies do not support this (Nickell, White, Larson, Renter, & Sanderson, 2011;Niskanen, Lindberg, & Traven, 2002;Sarrazin et al, 2014). Outbreaks of BVD pestiviruses have also occurred due to the persistence of the virus in the reproductive organs, ovaries and testes, of TI animals (Collins et al, 2009;Niskanen, Alenius, et al, 2002;Strong et al, 2015). While the risk of transmission by TI animals is considered much lower than the risk posed by PI animals, the full extent of viral shedding and persistence of virus in TIs and their ability to maintain infection within a population needs further investigation.…”
Section: Vertical Transmission Of Bvd Occurs When Bovine Pestivirusesmentioning
The significant economic impacts of bovine viral diarrhoea (BVD) virus have prompted many countries worldwide to embark on regional or national BVD eradication programmes. Unlike other infectious diseases, BVD control is highly feasible in cattle production systems because the pathogenesis is well understood and there are effective tools to break the disease transmission cycle at the farm and industry levels. Coordinated control approaches typically involve directly testing populations for virus or serological screening of cattle herds to identify those with recent exposure to BVD, testing individual animals within affected herds to identify and eliminate persistently infected (PI) cattle, and implementing biosecurity measures such as double‐fencing shared farm boundaries, vaccinating susceptible breeding cattle, improving visitor and equipment hygiene practices, and maintaining closed herds to prevent further disease transmission. As highlighted by the recent DISCONTOOLS review conducted by a panel of internationally recognized experts, knowledge gaps in the control measures are primarily centred around the practical application of existing tools rather than the need for creation of new tools. Further research is required to: (a) determine the most cost effective and socially acceptable means of applying BVD control measures in different cattle production systems; (b) identify the most effective ways to build widespread support for implementing BVD control measures from the bottom‐up through farmer engagement and from the top‐down through national policy; and (c) to develop strategies to prevent the reintroduction of BVD into disease‐free regions by managing the risks associated with the movements of animals, personnel and equipment. Stronger collaboration between epidemiologists, economists and social scientists will be essential for progressing efforts to eradicate BVD from more countries worldwide.
Bovine viral diarrhoea (BVD) is a significant drain on efficient and successful cattle production in both dairy and beef systems around the world. Several countries have achieved eradication of this disease, but always through the motivation of stakeholders who accept the benefits of eradication. These include increased cattle welfare and fitness of cattle to withstand other diseases, and decreased costs of production, the latter resulting from both decreased costs spent on managing the disease and decreased losses. This paper provides a systematic review of 31 papers, published between 1991 and 2015, that address the economic impact of BVD. Each paper takes a different approach, in either beef or dairy production or both. However with the breadth of work collated, a stakeholder engaged in BVD eradication should find an economic figure of most relevance to them. The reported economic impact ranges from £0 to £552 per cow per year (£2370 including outliers). This range represents endemic or subclinical disease situations seen in herds with stable BVD virus infection, and epidemic or severe acute situations, most often seen in naïve herds. The outcome of infection is therefore dependent on the immune status of the animal and severity of the strain. The variations in figures for the economic impact of BVD relate to these immune and pathogenicity factors, along with the variety of impacts monitored.
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