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Summary

More than 150 open, healthy heifers seronegative to both BVD Type 1 and Type 2 were vaccinated pre-breeding with a single minimum protective dose (MPD) of Vista™ 5 SQ to determine the efficacy of preventing fetal persistent infection caused by BVD Type 1 and Type 2. Heifers were randomized to two treatment groups: (1) the first group was vaccinated subcutaneously with a 2 mL, single MPD of Vista 5 SQ at four weeks pre-breeding; and (2) a second group consisted of controls receiving a placebo vaccination with sterile diluent. There were 68 heifers pregnant after breeding: 23

Vista 5 SQ BVD Type 1-challenged heifers, 22 Vista 5 SQ BVD Type 2-challenged heifers, 12 control BVD Type 1-challenged heifers, and 11 control BVD Type 2-challenged heifers. Vista 5 SQ vaccinated heifers developed specific serum neutralization (SN) antibody to BVD Type 1 and Type 2, with high titers following vaccination. All heifers were challenged at approximately 75 days in gestation with either Type 1 or Type 2 non-cytopathic BVD strains. To confirm infection of heifers by the challenge viruses, the heifers were evaluated in a two-week post-challenge period for rectal temperatures, clinical scores, white blood cell counts, viremia and viral shedding from the nasal cavity. All control heifers developed leukopenia (white blood cell decrease), clinical sickness and viremia after challenge, but Vista 5 SQ vaccinated heifers were protected from the challenge. Fetuses were collected at about 150 days of gestation from heifers, and tissue samples were taken for BVD virus isolation. Results demonstrated that 100% of fetuses from unvaccinated heifers were persistently infected following BVD Type 1 or Type 2 challenges. Vaccination with Vista 5 SQ provided 96% and 91% protection (P<.01 from="" fetal="" persistent="" infection="" for="" bvd="" type="" and="" respectively.="" vista="" sq="" is="" efficacious="" as="" an="" aid="" in="" the="" prevention="" of="" persistently="" infected="" calves="" caused="" by="">

Introduction

Persistently infected animals (PIs) born with either BVD Type 1 or Type 2 are considered a major source of infection for contact animals in all bovine production settings. Caused by infection in utero prior to Day 120 of gestation, it is also generally believed that these PIs are primarily responsible for maintaining BVD within the cattle population. In order to reduce or eliminate this costly infectious disease, vaccination to prevent fetal infection is necessary. The objective of these studies was to determine the efficacy of a single, pre-breeding vaccination with Vista 5 SQ at the MPD for the prevention of PI fetuses when pregnant heifers were challenged at 75-84 days of gestation with non-cytopathic BVD Type 1 and Type 2 viruses.

Materials and Methods

Immunoserial of Vista 5 SQ containing minimum protective dose (MPD) was prepared for all antigens (BVD Type 1 and Type 2, IBR, BRSV and PI3). More than 150 heifers, BVD seronegative and PI free (determined by immunohistochemistry, IHC), were used at the beginning of the study. For each study, all heifers were randomized to two treatment groups: vaccinates and control groups. Vaccinations (Vista 5 SQ for the vaccinates and sterile diluent for the controls) were administered four weeks pre-breeding.

The heifers were synchronized by feeding melengesterol acetate (MGA) for 14 days followed by a prostaglandin injection 16 days later. Breeding was started 4 to 5 weeks post-vaccination. The bulls used for breeding were also BVD PI negative as determined by IHC. Pregnancy of heifers was confirmed 6 to 7 weeks post-breeding by ultrasound. For the two challenge studies, sixty eight (68) heifers were pregnant. Thirty-five (35) heifers, 23 vaccinated and 12 unvaccinated controls, were used in the BVD Type 1 challenge. Thirty-three (33) heifers, 22 vaccinated and 11 controls, were challenged with BVD Type 2 strain.

Serum samples were collected at Day 0 (day of vaccination), at four weeks post-vaccination, and at the time of pregnancy checks and challenge to determine SN antibody titers to both BVD Type 1 and Type 2.

At about 75 days of gestation, all heifers were challenged with either BVD Type 1 or Type 2 non cytopathic strains. Clinical observations were made from Day -1 to Day 14 postchallenge. These observations included rectal temperatures and clinical signs associated with BVD disease. On Days post-challenge, EDTA-blood samples were collected for white blood cell and platelet counts. Nasal swab samples for virus isolation were collected on Days -1 to 10 postchallenge. Heparin blood was taken from animals on Days 0, 6 through 10 and 14 post-challenge, and buffy coats were collected for virus isolation to determine viremia.

At 150 to 165 days of gestation, the cows were humanely euthanized. Fetuses and placenta were collected for virus isolation. Tissue samples, including fetal thymus, lung, spleen, kidney, and intestine were taken and processed for BVD virus isolation. The isolated virus specificity and type were determined by fluorescent assay (FA) using BVD type-specific monoclonal antibodies.

Results and Discussion

Vista 5 SQ vaccinated heifers developed specific serum neutralizing (SN) antibody titers to BVD Type 1 and Type 2 in both trials, while the controls remained negative until challenge (Figures 1 through 4). About four weeks after vaccination (31 days post-vaccination for BVD Type 1 study, and 35 days post-vaccination for BVD Type 2 study), 100% of vaccinated heifers showed specific SN antibody titers to both BVD Type 1 and Type 2 .

Leukopenia (reduced white blood cell count) is a common sequel to BVD infection. After challenge, leukopenia was pronounced in the control heifers in both studies. Control heifers had lower (P<.05 white="" blood="" cell="" counts="" days="" through="" following="" bvd="" type="" challenge="" and="" compared="" to="" vista="" sq="" vaccinated="" heifers="" there="" was="" no="" difference="" in="" platelet="" between="" treatments="" both="">

Following challenge with BVD Type 1, control animals demonstrated higher (P<.05 rectal="" temperatures="" on="" day="" post-challenge="" while="" none="" of="" the="" vista="" sq="" vaccinated="" heifers="" developed="" a="" temperature="" higher="" than="" f.="">

Following the BVD Type 2 challenge, control heifers had numerically higher rectal temperatures, but temperatures were not different. However, on Day 7 post-challenge, three control heifers had temperatures higher than 104° F. None of the Vista 5 SQ vaccinated heifers had rectal temperatures exceeding 104° F (Figures 7 and 8).

Control heifers developed greater (P<.05 clinical="" signs="" on="" days="" through="" post-challenge="" with="" bvd="" type="" strain="" compared="" to="" vista="" sq="" vaccinated="" heifers="" following="" challenge="" the="" were="" very="" mild="" in="" all="" animals="" and="" there="" no="" differences="">.05) in clinical scores between the two treatment groups (Figure 10).

Virus shedding in the challenged animals is another good indication of infection. Following the BVD Type 1 and Type 2 challenges, all control heifers were positive for 2 to 5 days during the 10 day monitoring period. However, only three out of 45 vaccinated heifers (one of 23 heifers in the BVD Type 1 challenge study, and two of 22 heifers in the BVD

Type 2 challenge study) showed virus shedding for only one day. A higher (P<.05 portion="" of="" positive="" isolation="" in="" controls="" occurred="" on="" days="" through="" post-challenge="" and="">

Furthermore, control heifers were positive for more (P<.05 days="" compared="" to="" vista="" sq="" vaccinated="" heifers="" vs.="" in="" bvd="" type="" challenge="" and="" day="">

in BVD Type 2 challenge). The number of animals shedding per sampling period (P

Control heifers developed BVD viremia as indicated by isolation of virus from buffy-coat samples. Controls were viremic for more (P<.05 days="" compared="" to="" vista="" sq="" vaccinated="" heifers.="" there="" was="" a="" greater="" proportion="" of="" viremic="" heifers="" in="" the="" control="" group="" for="" and="" post-challenge="" bvd="" type="" challenge="" studies="" respectively="">

All the results of leukopenia, viremia, virus shedding and clinical scores strongly indicated that the control heifers were infected by the challenged BVD strains. The vaccinated heifers were successfully protected from the challenges.

Virus isolation from the fetus at about 150 days of gestation is the indication of fetal persistent infection (PI) resulting from challenge occurring at about 75 days of gestation. The results of virus isolation in our studies demonstrated that all (100%) 23 fetuses from the control heifers (12 in BVD Type 1 study, and 11 in Type 2 study) were positive. Only one of 23 fetuses (4%) from Vista 5 SQ vaccinated heifers was positive for BVD Type 1 infection (Figure 15). Only two of 22 Vista 5 SQ vaccinates (9%) yielded positive BVD Type 2 virus isolation in fetuses (Figure 16). There was a reduction (P

Conclusion

Vaccination of breeding-age heifers at four weeks pre-breeding with Vista 5 SQ aids in the prevention of persistently infected calves due to BVD Type 1 and Type 2. All control heifers developed leukopenia (white blood cell decrease), clinical sickness and viremia after challenge, but Vista 5 SQ vaccinated heifers were protected from the challenge. Study results demonstrated that heifers vaccinated with a single dose of Vista 5 SQ protected 96% and 91% of their fetuses from becoming persistently infected with BVD Type 1 and Type 2, respectively, following virulent challenge at 75-84 days of gestation with BVD Type 1 or Type 2 strains.