Abstract
Group A Rotavirus (RVA) is the leading cause of severe diarrhea in children. The aims of the present study were to determine the neutralizing activity of VP6-specific llama-derived single domain nanoantibodies (VHH nanoAbs) against different RVA strains in vitro and to evaluate the ability of G6P[1] VP6-specific llama-derived single domain nanoantibodies (VHH) to protect against human rotavirus in gnotobiotic (Gn) piglets experimentally inoculated with virulent Wa G1P[8] rotavirus. Supplementation of the daily milk diet with 3B2 VHH clone produced using a baculovirus vector expression system (final ELISA antibody -Ab- titer of 4096; virus neutralization -VN- titer of 256) for 9 days conferred full protection against rotavirus associated diarrhea and significantly reduced virus shedding. The administration of comparable levels of porcine IgG Abs only protected 4 out of 6 of the animals from human RVA diarrhea but significantly reduced virus shedding. In contrast, G6P[1]-VP6 rotavirus-specific IgY Abs purified from eggs of hyperimmunized hens failed to protect piglets against human RVA-induced diarrhea or virus shedding when administering similar quantities of Abs. The oral administration of VHH nanoAb neither interfered with the host's isotype profiles of the Ab secreting cell responses to rotavirus, nor induced detectable host Ab responses to the treatment in serum or intestinal contents. This study shows that the oral administration of rotavirus VP6-VHH nanoAb is a broadly reactive and effective treatment against rotavirus-induced diarrhea in neonatal pigs. Our findings highlight the potential value of a broad neutralizing VP6-specific VHH nanoAb as a treatment that can complement or be used as an alternative to the current strain-specific RVA vaccines. Nanobodies could also be scaled-up to develop pediatric medication or functional food like infant milk formulas that might help treat RVA diarrhea.
Highlights
Diarrhea is the second most common cause of childhood mortality worldwide, causing 1.3 million deaths among children younger than 5 years of age [1]
Against human RVA associated diarrhea in Gn piglets experimentally inoculated with virulent Wa G1P[8]I1 RVA, one of the most prevalent RVA strains circulating in human infants worldwide [15,16,17,18,19,20,21]
The experimental design included five groups of Gn pigs receiving milk supplemented with one of the following: 3B2 VHH nanoAbs (VHH produced against G6P[1]), Wa G1P[8]I1 human RVA-specific porcine IgG Abs (IgG), G6P[1] VP6-specific chicken IgY Abs (IgY), control larvae (CL) or Ab-free milk (No Treatment, NT)
Summary
Diarrhea is the second most common cause of childhood mortality worldwide, causing 1.3 million deaths among children younger than 5 years of age [1]. Group A rotavirus (RVA) is the leading cause of severe diarrhea in children worldwide and is responsible for approximately 29% of all diarrheal deaths, causing 453,000 deaths per year [2,3,4,5]. Human rotaviruses (Group A, B and C) have been implicated as causative agents of diarrheal outbreaks occurring in nursing homes [6], among travelers [7], in day-care centers [8], and in patients suffering from a variety of immunodeficiency conditions [9,10]. Most segments encode a single polypeptide, allowing the virus to express six structural proteins (VPs) and five non-structural proteins (NSPs) [11]. G-types G1 to G4 and G9 combined with P-types P[4], P[6] and P[8] account for most of Author Summary
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
