Influence of protein conformation and adjuvant aggregation on the effectiveness of aluminum hydroxide adjuvant in a model alkaline phosphatase vaccine.
The mechanism(s) of the enhancement of the immune response by addition of aluminum salt adjuvants to parenterally administered protein-based vaccines is still the subject of debate. It has been hypothesized, however, that destabilization of the antigen structure on the surface of the adjuvant may be important for eliciting immune response. Also, it has been suggested that immune response to adjuvanted vaccines is reduced if the adjuvant particles become aggregated before administration because of processing steps such as freeze-drying. In this study, we tested these hypotheses and examined the immune response in a murine model to various liquid, freeze-dried, and spray freeze-dried formulations of a model vaccine, bovine intestinal alkaline phosphatase adsorbed on aluminum hydroxide. Enzymatic activity of the alkaline phosphatase was used as a sensitive indicator of intact native antigen structure. By manipulating the secondary drying temperature during lyophilization, vaccines were produced with varying levels of alkaline phosphatase enzymatic activity and varying degrees of adjuvant aggregation, as assessed by particle size distribution. Anti-alkaline phosphatase titers observed in immunized mice were independent of both the antigen's retained enzymatic activity and the vaccine formulation's mean particle diameter.
Department of Chemical and Biological Engineering, Center for Pharmaceutical Biotechnology, ECCH 111, Campus Box 424, University of Colorado, Boulder, Colorado 80309, USA.
Amber L
AL
Clausi
Andrea
A
Morin
John F
JF
Carpenter
Theodore W
TW
Randolph
D000277:Adjuvants, Pharmaceutic / Q000008:administration & dosage*; D000469:Alkaline Phosphatase / Q000008:administration & dosage* / Q000276:immunology; D000536:Aluminum Hydroxide / Q000008:administration & dosage* / Q000276:immunology; D000537:Aluminum Oxide / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D002417:Cattle; D005260:Female; D007117:Immunization, Secondary; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D010316:Particle Size; D011208:Powders; D011487:Protein Conformation; D012996:Solutions; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000276:immunology
D000277:Adjuvants, Pharmaceutic; D007074:Immunoglobulin G; D011208:Powders; D012996:Solutions; D014614:Vaccines, Synthetic; D007073:Immunoglobulin E; D000536:Aluminum Hydroxide; C069471:aluminum oxide hydroxide; D000469:Alkaline Phosphatase; D000537:Aluminum Oxide