Production of Oral Vaccines Based on Retrovirus Virus-like Particles Pseudotyped with Protozoan-Surface Proteins

Abstract

Giardia lamblia is the only known parasite that can inhabit the harsh upper gastrointestinal tract, wheremost of the digestive proteases are secreted. Intestinal and free-living protozoa express surface proteinscontaining an extraordinarily high percentage of cysteine. These cysteine-rich variant-specific surfaceproteins (VSPs) form a dense coat on the entire surface of Giardia trophozoites, that coat protects theparasite inside the host intestine. VSPs not only are resistant to proteolytic digestion, extreme pH andtemperatures, but also stimulate host immune responses. These properties can be used to protect as well asto increase the immunogenicity of vaccine antigens for oral administration. The incorporation of VSPs ontovirus-like particles bearing viral antigens allows oral administration of these vaccines, protecting theantigens from degradation and generating robust and protective immune responses. In this chapter wedescribe the development of this versatile vaccine platform for the generation of safe, stable, and efficientoral vaccines, including their production and validation, as well as the characterization of immune responseto oral immunization.