Data from: Novel BPI3Vc-vectored chimeric BVDV antigens elicit broadly neutralizing antibodies in cattle

Bovine Viral Diarrhea Virus (BVDV) is a key contributor to the development
of Bovine Respiratory Disease complex, which can cause respiratory
disease, congenital defects, severe diarrhea, immunosuppression, abortion,
or birth of persistently infected calves. Current commercial vaccines are
formulated using strains from BVDV-1a and BVDV-2a, conferring protection
against some, but not all, homologous species and low neutralization
titers against heterologous and emergent species. This study aimed to
develop a live vaccine capable of inducing broad protection against
diverse BVDV strains. A contemporary live-attenuated BPI3Vc-vectored BVDV
prototype vaccine was developed. Novel chimeric BVDV E2-NS2-51-2 antigens,
designed based on the consensus of all BVDV-1a, -1b, -2a, -2b, and -2c
protein sequences, were used to generate recombinant
BPI3VcmutantE2-NS2-51-2 viruses. The recombinant viruses expressed all the
5kb encoded transgenes, replicated efficiently, remained genetically
stable over nine passages in vitro, and displayed the E2 ectodomain on the
surface of infected cells. Intranasal immunization of calves with a
cocktail of these recombinant viruses, designated rBPI3VcmutBVDV, elicited
strong serum antibodies against BVDV-1 and -2 viruses compared to a
commercial vaccine. Notably, vaccination elicited stronger IgG responses
against BVDV-1b CA0401186a and TGAC, with significantly higher
virus-neutralizing titers than the commercial vaccine (CA0401186a:
p=0.0031; TGAC: p=0.0002). Immunized calves also elicited significantly
higher VN titers against BVDV-2a strains 296NC (p=0.0006), 890 (p=0.0020),
296C (p=0.0464), A125 (p=0.0018), and 1373 (p=0.0025). Upon challenge with
BVDV-1b CA0401186a, the rBPI3Vcmut~BVDV vaccinees exhibited a steady
weight gain, a slight decrease in lymphocyte counts, lower viremia, and
fewer gross lesions. This data supports the use of the live-attenuated
BPI3Vc-vector for the development of contemporary broadly protective BVDV
vaccines that can easily be upgraded for improved disease management and
cattle productivity.