Liposomal co-entrapment of CD40mAb induces enhanced IgG responses against bacterial polysaccharide and protein.
BACKGROUND
Antibody against CD40 is effective in enhancing immune responses to vaccines when chemically conjugated to the vaccine antigen. Unfortunately the requirement for chemical conjugation presents some difficulties in vaccine production and quality control which are compounded when multivalent vaccines are required. We explore here an alternative to chemical conjugation, involving the co-encapsulation of CD40 antibody and antigens in liposomal vehicles.


RESULTS
Anti-mouse CD40 mAb or isotype control mAb were co-entrapped individually in cationic liposomal vehicles with pneumococcal polysaccharides or diphtheria and tetanus toxoids. Retention of CD40 binding activity upon liposomal entrapment was assessed by ELISA and flow cytometry. After subcutaneous immunization of BALB/c female mice, anti-polysaccharide and DT/TT responses were measured by ELISA. Simple co-encapsulation of CD40 antibody allowed for the retention of CD40 binding on the liposome surface, and also produced vaccines with enhanced imunogenicity. Antibody responses against both co-entrapped protein in the form of tetanus toxoid, and Streptococcus pneumoniae capsular polysaccharide, were enhanced by co-encapsulation with CD40 antibody. Surprisingly, liposomal encapsulation also appeared to decrease the toxicity of high doses of CD40 antibody as assessed by the degree of splenomegaly induced.


CONCLUSIONS
Liposomal co-encapsulation with CD40 antibody may represent a practical means of producing more immunogenic multivalent vaccines and inducing IgG responses against polysaccharides without the need for conjugation.
Adjuvantix Ltd, Sheffield, United Kingdom.
Caterina
C
Hatzifoti
Andrew
A
Bacon
Helen
H
Marriott
Peter
P
Laing
Andrew W
AW
Heath
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology*; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C
D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D019013:CD40 Antigens; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D008081:Liposomes