Bovine Virus Diarrhea

Virus Vaccines

■ TABLE 48.9

Currently Licensed Vaccines for Bovine Virus Diarrhea Virus

^aM = modified live BVDV comρonent(s); K = killed BVDV comρonent(s).

Vaccination and Mucosal Disease

Mucosal disease (MD) is seen when an animal that is persistently infected is exposed to another closely related cytopathic strain of BVDV Also, theoretically a noncytopathic BVDV strain can mutate spontaneously into a cytopathic strain, resulting in MD without any subsequent exposure. High stress and immunodepression may be involved in this mutation.^17,18

A major concern with the MLV vaccines is whether they can cause MD.^10,19,20 For MD to occur, the cytopathic strain in the MLV vaccine must be closely related to the noncytopathic strain in the persistently infected animal. With the degree of attenuation of MLV vaccines today, an animal must be nutrition­ally deficient or severely stressed, or both, to face an increased likelihood of developing MD from the vaccine. This suggests that a specific set of circumstances is required and that MD caused by vaccination, when it occurs, is rare.

Bovine Virus Diarrhea Virus Vaccines and Reproductive Control

Control of BVDV centers on prevention of persistent infection and elimination of persistently infected cattle; this means identifying and removing persistently infected animals and continued vaccination to prevent persistent infection are necessary for effective control. Persistent infections occur through in utero infection of the fetus (up to roughly 125 days' gestation) with a noncytopathic strain of BVDV^3,17 Although the mechanism of transplacental transfer of BVDV is unknown, small amounts of virus in the dam's bloodstream appear to be sufficient to produce these immunotolerant cattle. Protection of the dam may or may not correlate with protection of the fetus from subsequent persistent infection if viremia of the dam occurs. To break the cycle of in utero infection and persistent infection, it is essential that vaccination provide fetal protection.

Several studies have been performed to assess the ability of vaccines to protect the fetus against either natural or artificial challenge. Results of these studies showed that most inactivated vaccines failed to provide much fetal protection,^7,10,21-26 except for one experimental vaccine, which is reported to give a high level of fetal protection. With the experimental vaccine, inability to isolate the virus from offspring of vaccinated animals indicated good protection.²⁷ However, the challenge of controls resulted in only about a 50% rate of persistent infection. Only one inactivated vaccine has demonstrated a high level of fetal protection and was given the appropriate label by the USDA (see Table 48.8). Other published reports demonstrated that MLV BVDV vaccines were more effective at protecting the fetus^7,28-30 and that inclusion of a type 2 vaccine broadened the strains against which vaccinates were protected.³¹ To date, vaccines licensed in the United States have not been required to provide fetal protection. However, label indications are being granted by the USDA to vaccines that demonstrated the ability to prevent development of persistently infected calves. Several vaccines have achieved this label claim (see Table 48.8).

Bovine Virus Diarrhea Virus Vaccination Programs

Because BVDV infections can cause severe death loss and immunosuppression, all herds of cattle should be vaccinated against BVDV. Although it was once thought that BVDV vaccines would not immunize calves that were passively immune to BVDV,^32,33 recent studies have shown that immunization can occur with certain inactivated vaccines³⁴ and with MLV vaccines (when the passive antibody titer against BVDV is ≤1 : 64).^13,35 When required, BVDV vaccines can be administered to young calves, with the possibility of gaining some degree of protection. In most calves the maternal antibodies against BVDV drop below the 1: 64 level by 5 to 6 months of age.

Among cows given MLV BVDV vaccines in the last trimester of pregnancy, 86% of the calves from seronegative cows³⁶ and some calves (0³⁶ to 52%³⁷) from seropositive dams were actively immune at birth. In addition, the calves' level of passive immunity to BVDV was enhanced, in that seronegative cows seroconverted and serum antibody titers were boostered in 52% of the seropositive cows. The rate of occurrence of BVD in neonatal calves was reduced.³⁸ Administration of an MLV BVDV vaccine to seronegative cows after day 118 of gestation did not result in adverse effects.^38,39 However, vaccination with an MLV noncytopathic virus vaccine before day 118 resulted in fetal resorption, abortion, congenital defects, and the birth of undersized, weak, persistently infected calves. Several authors have recommended vaccination of cows with an MLV BVDV vaccine during the last trimester of pregnancy.²² Three MLV BVDV vaccines are now labeled for use in pregnant animals. To ensure the safety of these vaccination schedules, label directions must be adhered to.

It is important to consider the epidemiologic nonresponse rate to any vaccine when designing a BVDV vaccination program. Therefore even though MLV BVDV vaccines do not require a booster dose, a second dose may be advised to stimulate protection in animals that did not respond to the initial vaccination. BVDV vaccination programs should include the following features:

1. A virus isolation and cull program should be instituted, along with a vaccination program that includes administration of at least one dose of an MLV BVDV vaccine to all replace­ment animals.

2. Vaccination with killed vaccines should be increased to 2 or 3 times a year, or an MLV BVDV vaccine should be given to open cows 3 weeks before breeding or turning in the bull.

3. The vaccines used should have been proved to stimulate protection against BVDV type 1 and type 2.