Rational design of the first commercially available subunit vaccine
against BVDV targeted to immune system cells
Bovine viral diarrhea virus (BVDV) is a major cause of economic loss in
the cattle industry, worldwide. Infection results in reduce productive
performance, growth retardation, reduced milk production, and increased
susceptibility to other diseases leading to early culling of animals.
There are two main measures used to control the spread of BVDV: the
elimination of persistently infected (PI) animals and vaccination.
Currently, modified live or inactivated vaccines are used in BVDV
vaccination programs, but there are safety risks or insufficient
protection, respectively, with these vaccines. Here we report the
development and efficacy of the first targeted subunit vaccine against
BVDV. The core of the vaccine is a fusion of the BVDV structural
protein, E2, to a single-chain antibody, APCH, together termed, APCH-E2.
The APCH antibody targets the E2 antigen to the major histocompatibility
type II molecule (MHC-II) present on antigen-presenting cells.
Industrial production of the vaccine is carried out using the
baculovirus expression vector system (BEVS) using single-use
manufacturing technologies. This new subunit vaccine induces strong
BVDV-specific neutralizing antibodies in guinea pigs and cattle.
Importantly, in cattle with low levels of natural BVDV-specific
neutralizing antibodies, the vaccine induced strong neutralizing
antibody levels to above the protective threshold, as determined by a
competition ELISA. The APCH-E2 vaccine induced a rapid and sustained
neutralizing antibody response compared to a conventional vaccine in
cattle. The development of this subunit targeted vaccine provides cattle
and dairy producers with an inexpensive, easily administered, safe, and
efficacious BVDV vaccine.