Preclinical evaluation of the saponin derivative GPI-0100 as an immunostimulating and dose-sparing adjuvant for pandemic influenza vaccines.
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.
Department of Medical Microbiology, Molecular Virology Section, University Medical Center and University of Groningen, Groningen, The Netherlands.
Heng
H
Liu
Laura
L
Bungener
Wouter
W
ter Veer
Beth-Ann
BA
Coller
Jan
J
Wilschut
Anke
A
Huckriede
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004306:Dose-Response Relationship, Immunologic; D004353:Drug Evaluation, Preclinical; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000097:blood; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D012503:Saponins / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; C484998:GPI0100; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D012503:Saponins; D022223:Vaccines, Subunit; C483468:hemagglutinin, human influenza A virus