RESUMEN
Peptide antigens are combined with an adjuvant in order to increase immunogenicity in vivo. The immunogenicity and safety of a RSV vaccine formulated in a novel oil-based platform, DepoVax™ (DPX), was compared to an alum formulation. A peptide B cell epitope derived from RSV small hydrophobic ectodomain (SHe) served as the antigen. Both vaccines induced SHe-specific antibodies after immunization of mice. A single dose of the DPX-based formulation resulted in anti-SHe titres for up to 20 weeks. Boosting with Alum-SHe, but not with DPX-SHe, led to unexpected clinical signs such as decreased activity, cyanosis and drop in body temperature in mice but not in rabbits. The severity of adverse reactions correlated with magnitude of SHe-specific IgG immune responses and decreased complement component 3 plasma levels, indicating a type III hypersensitivity reaction. By RP-HPLC analysis, we found that only 8-20% of the antigen was found to be adsorbed to alum in vitro, indicating that this antigen is likely released systemically upon injection in vivo. Clinical signs were not observed in rabbits, indicating the response correlates with peptide dose relative to size of animal. These results suggest that peptide antigens targeted to produce B cell mediated response may result in increased incidence of type III hypersensitivity reactions when delivered in non-depot forming vaccines. The DPX formulation induced strong antibody titres to the antigen without causing adverse events, likely due to the strength of the depot in vivo, and demonstrates the potential safety and immunogenicity of this platform for B cell peptide antigens.
Asunto(s)
Adyuvantes Inmunológicos/efectos adversos , Epítopos de Linfocito B/inmunología , Enfermedades del Complejo Inmune/inmunología , Infecciones por Virus Sincitial Respiratorio/prevención & control , Vacunas contra Virus Sincitial Respiratorio/inmunología , Virus Sincitiales Respiratorios/inmunología , Adyuvantes Inmunológicos/química , Compuestos de Alumbre/efectos adversos , Compuestos de Alumbre/química , Animales , Preparaciones de Acción Retardada/efectos adversos , Preparaciones de Acción Retardada/química , Evaluación Preclínica de Medicamentos , Femenino , Enfermedades del Complejo Inmune/epidemiología , Inmunogenicidad Vacunal , Incidencia , Ratones , Aceites/efectos adversos , Aceites/química , Conejos , Infecciones por Virus Sincitial Respiratorio/inmunología , Infecciones por Virus Sincitial Respiratorio/virología , Vacunas contra Virus Sincitial Respiratorio/efectos adversos , Vacunas contra Virus Sincitial Respiratorio/química , Vacunación/métodos , Vacunas de Subunidad/efectos adversos , Vacunas de Subunidad/química , Vacunas de Subunidad/inmunología , Vacunas Sintéticas/efectos adversos , Vacunas Sintéticas/química , Vacunas Sintéticas/inmunologíaRESUMEN
A single dose formulation of a novel hepatitis B vaccine, consisting of an adjuvant emulsion of liposomes in oil was produced at a manufacturing scale and delivered to rabbits. This single dose vaccine generated a significantly higher antibody response than two doses of an alum-adjuvanted control vaccine in the short term, and was as effective as three doses of the control vaccine in the long term.