MF59 adjuvant enhances antibody responses of infant baboons immunized with Haemophilus influenzae type b and Neisseria meningitidis group C oligosaccharide-CRM197 conjugate vaccine.
The ability of the adjuvant MF59 to enhance the immunogenicity of polysaccharide-protein conjugate vaccines was investigated in infant baboons. MF59 consists of stable droplets (<250 nm) of the metabolizable oil squalene and two surfactants, polyoxyethylene sorbitan monooleate and sorbitan trioleate, in an oil-in-water emulsion. In humans, MF59 is well tolerated and enhances the immunogenicity of recombinant protein subunit or particle vaccines. Its effect on the immunogenicity of polysaccharide-protein conjugate vaccines is unknown. Baboons 1 to 4 months of age were immunized intramuscularly with Neisseria meningitidis group C and Haemophilus influenzae type b (Hib) oligosaccharide-CRM197 conjugate vaccines. The lyophilized vaccines were reconstituted with phosphate-buffered saline (PBS), Al(OH)3 (alum), or MF59. Groups of five animals each were given three injections of the respective formulations, with one injection every 4 weeks. Four weeks after each immunization, the MF59 group had up to 7-fold-higher geometric mean anticapsular-antibody titers than the alum group and 5- to 10-fold-higher N. meningitidis group C bactericidal-antibody titers. Twenty-one weeks after the third immunization, the MF59 group still showed 5- to 10-fold-higher anticapsular-antibody titers. The antibody responses of the animals given the vaccines reconstituted with PBS were low at all times measured. Both the MF59 and alum groups, but not the PBS group, showed booster antibody responses to unconjugated Hib and N. meningitidis group C polysaccharides, results consistent with induction of memory B cells. Thus, MF59 may be useful for accelerating and augmenting immunity to polysaccharide-protein conjugate vaccines in infants.
Granoff
D M
DM
Chiron Vaccines, Emeryville, California 94608, USA. danvgranoff@cc.chiron.com
McHugh
Y E
YE
Raff
H V
HV
Mokatrin
A S
AS
Van Nest
G A
GA
D000534:Alum Compounds / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D005260:Female; D006192:Haemophilus Infections / Q000276:immunology* / Q000517:prevention & control*; D006193:Haemophilus influenzae / Q000276:immunology*; D007156:Immunologic Memory; D008297:Male; D008585:Meningitis, Meningococcal / Q000276:immunology* / Q000517:prevention & control*; D009844:Oligosaccharides / Q000276:immunology*; D010215:Papio; D011135:Polysaccharides, Bacterial / Q000276:immunology; D011136:Polysorbates / Q000008:administration & dosage / Q000378:metabolism*; D013185:Squalene / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism*; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology*
D000534:Alum Compounds; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C089950:MF59 oil emulsion; D009844:Oligosaccharides; D011135:Polysaccharides, Bacterial; D011136:Polysorbates; D018074:Vaccines, Conjugate; C028581:CRM197 (non-toxic variant of diphtheria toxin); C041524:aluminum sulfate; D013185:Squalene