BI-Specific Diabodies For Masking And Targeting Vaccines

Abstract

The present invention describes compositions and methods for priming protective immunity in the presence of pre-existing maternal antibody. In some embodiments, the invention contemplates simultaneously masking vaccines to avoid antibody neutralization while targeting those vaccines to specific cell types in order to elicit an enhanced immune response. In other embodiments, vectors that recruit and activate specific antigen-presenting cells may further enhance the efficacy of those immune responses.

Description

STATEMENT OF GOVERNMENT SUPPORT[0001]This invention was made with government support awarded by the USDA-NIFA (USDA-CSREES 2008-35204-04587). The government has certain rights in the invention.FIELD OF THE INVENTION[0002]The present invention relates generally to the field of live and modified live conventional vaccines, and recombinant live-vectored vaccines. For example, compositions and methods are described that are useful for priming robust adaptive immunity in the presence of pre-existing protective / neutralizing levels of maternal antibodies and / or effective boosting of weak immune responses using the same live vaccines or live-vectored vaccines. In some embodiments, simultaneously masking vaccines to avoid antibody neutralization while targeting those vaccines to specific cell types elicits an enhanced immune response. In other embodiments, the efficacy of the immune responses may be further enhanced using vectors that recruit and activate specific antigen-presenting cells.BA...

AI Technical Summary

Benefits of technology

The present invention is about a new vaccine that can protect against BVDV, a cattle virus. The vaccine contains a bi-specific diabody that fuses a virus-masking motif with a cell-receptor binding motif. The virus-masking motif is a single chain antibody that binds to BVDV, while the cell-receptor binding motif is a single chain antibody that binds to dendritic cells. The vaccine also includes a recombinant adenovirus that expresses dendritic cell recruitment and activation factors. The vaccine can be a live vaccine or a modified live vaccine. The technical effect of this invention is to provide a more effective vaccine that can protect against BVDV infection in cattle.

Problems solved by technology

Bovine viral diarrhea virus (BVDV) is a leading cause of enteric, respiratory and reproductive diseases in cattle, and is particularly associated with high morbidity and mortality rates in calves.

While maternal antibodies protect neonatal calves and yearlings against wild-type (wt) BVDV infections, their high titers interfere with the efficacy of current BVDV vaccines.

Unfortunately, persistently infected (PI) calves are common in herds and yearlings become vulnerable to infection as BVDV-specific antibodies decline (12, 13, 15).

Moreover, maternal antibodies do not adequately protect a significant proportion of neonatal calves—especially bull calves that fail to get sufficient amounts of colostrum on time.

Images