Long-Term Sterilizing Immunity to Rinderpest in Cattle Vaccinated with a Recombinant Vaccinia Virus Expressing High Levels of the Fusion and Hemagglutinin Glycoproteins

Abstract

Rinderpest is an acute and highly contagious viral disease of ruminants, often resulting in greater than 90% mortality. We have constructed a recombinant vaccinia virus vaccine (v2RVFH) that expresses both the fusion (F) and hemagglutinin (H) genes of rinderpest virus (RPV) under strong synthetic vaccinia virus promoters. v2RVFH-infected cells express high levels of the F and H glycoproteins and show extensive syncytium formation. Cattle vaccinated intramuscularly with as little as 10 3 PFU of v2RVFH and challenged 1 month later with a lethal dose of RPV were completely protected from clinical disease; the 50% protective dose was determined to be 10 2 PFU. Animals vaccinated with v2RVFH did not develop pock lesions and did not transmit the recombinant vaccinia virus to contact animals. Intramuscular vaccination of cattle with 10 8 PFU of v2RVFH provided long-term sterilizing immunity against rinderpest. In addition to being highly safe and efficacious, v2RVFH is a heat-stable, inexpensive, and easily administered vaccine that allows the serological differentiation between vaccinated and naturally infected animals. Consequently, mass vaccination of cattle with v2RVFH could eradicate rinderpest.

Recombinant Rift Valley fever vaccines induce protective levels of antibody in baboons and resistance to lethal challenge in mice

“…1) using homologous recombination (19) and transient dominant selection (20). One rVACV expresses the RVFV glycoproteins (Gn and Gc) under the control of a strong VACV synthetic promoter (vCOGnGc) (17,21) and the second expresses the human IFN-γ (HuIFNγ) gene in addition to the two RVFV glycoproteins (vCOGnGcγ). The HuIFNγ gene was added to enhance safety for human vaccinators (22,23).…”

“…Our laboratory has extensive experience in developing rVACVs for the control of a number of human and animal diseases (17,18,22,24,34,35). Multiple approaches have been used to enhance the safety of poxviruses, including deletion or insertional inactivation of genes that enhance virulence, expression of cytokines, development of replication-deficient VACVs, such as MVA and NYVAC, or host cell-restricted vectors, such as canarypox and fowlpox (39)(40)(41)(42).…”

“…Thus, we have used our considerable experience in developing recombinant vaccinia viruses (rVACVs) (17,18) to construct two safe and efficacious, livestock vaccines for RVF. These vaccines express the two surface glycoproteins (Gn and Gc) to induce protective immunity to RVFV; one vaccine also expresses the human IFN-γ gene to enhance safety for vaccinators.…”

MVA recombinants expressing the fusion and hemagglutinin genes of PPRV protects goats against virulent challenge

“…The use of single VV [38] and Capri poxvirus vectors [39] expressing either the F or H protein of RPV, showed anamnestic responses that indicated replication of the challenge virus shortly after challenge, and long-term studies showed only partial protection [40]. In contrast, the double vaccinia recombinant expressing both the F and H proteins of PPRV v2RVFH provided complete protection with sterilizing immunity during both short-and long-term studies [41].…”

Lower Levels of Gamma Interferon Expressed by a Pseudotyped Single-Cycle Simian Immunodeficiency Virus Enhance Immunogenicity in Rats

“…In order to evaluate vaccine efficiency, we constructed a VV (WR strain) expressing SIV Gag-Pol to be used as a surrogate challenge (2,46). The gag-pol open reading frame was cloned by PCR and inserted under the dsP which were previously demonstrated to result in increased levels of expression compared to VV natural promoters (49). The gag-pol fragment was then introduced into the VV genome through homologous recombination and insertional inactivation of the VV B8R gene, generating vSIVgag-pol.…”