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Bovine Viral Diarrhea Virus Serum Neutralization

Since the recognition of an agent referred to as viral diarrhea virus in 1946, the virus responsible for clinical disease in bovines has undergone numerous classifications and name changes. Over the past 40 years, the name "bovine viral diarrhea virus" or BVDV became the entity responsible for major economic losses in the bovine industry. Currently, BVDV is in the Flaviviridae family, Pestivirus genus which now has 11 species including BVDV (Pestivirus, A, B, H), border disease virus (Pestivirus D), and classical swine fever virus (Pestivirus C). BVDV type 1 (pestivirus A), BVDV type 2 (pestivirus B), and Hobi-like viruses (pestivirus H) designations have a presence in the clinical literature that defines diagnostics, vaccination efficacy, and management programs. For these reasons, the "popular" nomenclature will be used for the discussion on the significance of virus neutralization data.

Initial attempts to control BVDV by vaccination used several isolates such as Singer, NADL and C24V. All of these when technology permitted typed as BVDV-1. Initial studies on serological cross-reactivity among BVDV isolates concluded that there were no defined serotypes and therefore all vaccines should be protective. In point of fact, the vaccines did prevent clinical disease in vaccinated animals challenged with field strains of virus. With the identification of persistently infected (PI) animals that come about by in utero infection, the "protection" of the fetus became a new criterion for evaluating the efficacy of vaccines. Shortly after the identification of the PI animal as a major factor in the spread of BVDV, a new BVDV virus referred to as BVDV type 2 was identified. Challenge of pregnant animals vaccinated with killed type 1 vaccines by type 2 virus clearly showed the need for inclusion of type 2 virus in vaccines. The cross-reactivity of antibodies against type 1 virus was not sufficient to prevent fetal infection by type 2 viruses. More recently a new species of BVDV was identified (Hobi-like viruses) in South America, Europe, and Southeast Asia. Limited studies strongly suggest that were this type of virus to be introduced into North America, currently available vaccines would be unlikely to offer strong fetal protection.

The interpretation of neutralization data related to BVDV is largely dependent upon knowing the vaccination history of the target animals. Most critical is the type of vaccine used – killed or modified live. Second major factor is the time post vaccination when the sample was collected. In general, killed vaccine titers several months post vaccination will range from 32-256 while modified-live titer will range from 512- 1536. A non-immune animal infected with wild type virus will have titers early post infection in the low to mid-thousand range, but will fall back to titers similar to modified-live vaccinated animals. Animals vaccinated with killed vaccine and challenged with wild type virus will have early titers ranging from 5000-20,000 and will stabilize at values higher than modified live vaccinated animals. In general PI animals will have no or low Ab titers. As with all serological tests, having acute and convalescent serum samples may provide definitive proof of recent infection.

The AHDC offers routine testing for antibodies that neutralize BVDV types 1 & 2. Under special circumstances, we can screen for antibodies that recognize Hobi-like viruses. When deciding whether to test for antibodies for type 1 or 2 BVDV by SN, please consider the following:

  • If the animal has been vaccinated with any strain of BVDV, there is no need to do both tests as an exposure will stimulate high titer cross-reacting antibodies between both 1 and 2.
  • If there has been no vaccination (sentinel calf program), then both tests should be requested, as a low value to one type might show a 10-fold higher unequivocal titer to the other type. In this instance, the higher titer value would be indicative of an infection with that type of virus.

The chart below represents titer values reported by the AHDC over the past 3 years. NOTE: Antibody titers at the AHDC are reported as the reciprocal of the dilution at the endpoint, e.g., 1:64 = 64