Rotavirus-induced
diarrhea causes more than 500,000 deaths annually in the world, and although
vaccines are being made available, new effective treatment strategies should still be considered. Purified
antibodies derived from hyperimmune bovine colostrum (HBC), from cows immunized with rotavirus, were previously used for treatment of rotavirus
diarrhea in children. A combination of HBC
antibodies and a probiotic strain of Lactobacillus (L. rhamnosus GG) was also found to be more effective than HBC alone in reducing
diarrhea in a mouse model of
rotavirus infection. In order to further improve this form of treatment, L. rhamnosus GG was engineered to display surface expressed
IgG-binding domains of
protein G (GB1, GB2, and GB3) which capture HBC-derived
IgG antibodies (HBC-
IgG) and thus target rotavirus. The expression of
IgG-binding domains on the surface of the bacteria as well as their binding to HBC-
IgG and to rotavirus (simian strain RRV) was demonstrated by Western blot, flow cytometry, and electron microscopy. The prophylactic effect of engineered L. rhamnosus GG and anti-rotaviral activity of HBC
antibodies was evaluated in a mouse pup model of RRV
infection. The combination
therapy with engineered L. rhamnosus GG (PG3) and HBC was significantly more effective in reducing the prevalence, severity, and duration of
diarrhea in comparison to HBC alone or a combination of wild-type L. rhamnosus GG and HBC. The new
therapy reduces the effective dose of HBC between 10 to 100-fold and may thus decrease treatment costs. This antibody capturing platform, tested here for the first time in vivo, could potentially be used to target additional gastrointestinal pathogens.