gpi0100 and Orthomyxoviridae-Infections

Adjuvants can stimulate vaccine-induced immune responses and can contribute decisively to antigen dose sparing when vaccine antigen production is limited, as for example during a pandemic influenza outbreak. We earlier showed that GPI-0100, a semi-synthetic saponin derivative with amphiphilic structure, significantly stimulates the immunogenicity and protective efficacy of influenza subunit vaccine administered via a systemic route. Here, we evaluated the adjuvant effect of GPI-0100 on a virosomal influenza vaccine formulation. In contrast to influenza subunit vaccine adjuvanted with GPI-0100, virosomal vaccine supplemented with the same dose of GPI-0100 provided full protection of mice against infection at the extremely low antigen dose of 2 × 8 ng hemagglutinin. Overall, adjuvanted virosomes elicited higher antibody and T-cell responses than did adjuvanted subunit vaccine. The enhanced immunogenicity of the GPI-0100-adjuvanted virosomes, particularly at low antigen doses, is possibly due to a physical association of the amphiphilic adjuvant with the virosomal membrane. These results show that a combination of GPI-0100 and a virosomal influenza vaccine formulation is highly immunogenic and allows the use of very low antigen doses without compromising the protective potential of the vaccine.

Topics: Adjuvants, Immunologic; Animals; Antigens, Viral; Cell Line; Disease Models, Animal; Dogs; Female; Immunity, Cellular; Immunity, Humoral; Influenza A Virus, H1N1 Subtype; Influenza Vaccines; Mice; Orthomyxoviridae Infections; Saponins; Vaccines, Subunit; Vaccines, Virosome

Identification of safe and effective adjuvants remains an urgent need for the development of inactivated influenza vaccines for mucosal administration. Here, we used a murine challenge model to evaluate the adjuvant activity of GPI-0100, a saponin-derived adjuvant, on influenza subunit vaccine administered via the intranasal or the intrapulmonary route. Balb/c mice were immunized with 1 µg A/PR/8 (H1N1) subunit antigen alone or in combination with varying doses of GPI-0100. The addition of GPI-0100 was required for induction of mucosal and systemic antibody responses to intranasally administered influenza vaccine and significantly enhanced the immunogenicity of vaccine administered via the intrapulmonary route. Remarkably, GPI-0100-adjuvanted influenza vaccine given at a low dose of 2×1 µg either in the nares or directly into the lungs provided complete protection against homologous influenza virus infection.

Topics: Adjuvants, Immunologic; Administration, Intranasal; Animals; Antibodies, Viral; Female; Immunoglobulin A, Secretory; Immunoglobulin G; Influenza A Virus, H1N1 Subtype; Influenza Vaccines; Lung; Mice; Mucous Membrane; Orthomyxoviridae Infections; Saponins; T-Lymphocytes, Helper-Inducer; Vaccines, Subunit

With the current global influenza vaccine production capacity the large demand for vaccines in case of a pandemic can only be fulfilled when antigen dose sparing strategies are employed. Here we used a murine challenge model to evaluate the potential of GPI-0100, a semi-synthetic saponin derivative, to serve as a dose-sparing adjuvant for influenza subunit vaccine. Balb/c mice were immunized with different doses of A/PR8 (H1N1) subunit antigen alone or in combination with varying doses of GPI-0100. The addition of GPI-0100 significantly stimulated antibody and cellular immune responses, especially of the Th1 phenotype. Furthermore, virus titers detected in the lungs of mice challenged one week after the second immunization were significantly reduced among the animals that received GPI-0100-adjuvanted vaccines. Remarkably, adjuvantation of subunit vaccine with GPI-0100 allowed a 25-fold reduction in hemagglutinin dose without compromising the protective potential of the vaccine.

Topics: Adjuvants, Immunologic; Animals; Antibodies, Viral; Dose-Response Relationship, Immunologic; Drug Evaluation, Preclinical; Female; Hemagglutinin Glycoproteins, Influenza Virus; Immunity, Cellular; Immunity, Humoral; Immunoglobulin G; Influenza A Virus, H1N1 Subtype; Influenza Vaccines; Lung; Mice; Mice, Inbred BALB C; Orthomyxoviridae Infections; Saponins; Vaccines, Subunit