Development of an adjuvant-active nonionic block copolymer for use in oil-free subunit vaccines formulations.
Nonionic block copolymers, synthesized from repeating units of oxypropylene and oxyethylene, can be designed so that individual copolymers have unique physical properties with differential levels of adjuvant activity. We have designed high molecular weight block copolymers that spontaneously assemble into 500 nm-3 mum particles when formulated with protein antigens in aqueous solutions at physiological pH. The adjuvant activity of one of these copolymers, termed CRL1005, was compared to selected research adjuvants using ovalbumin (OVA) as the prototype vaccine antigen. Suboptimal doses of OVA were formulated with complete and incomplete. Freund's adjuvant (CFA/IFA), alum Quil-A saponins Ribi Adjuvant System (RAS) or the CRL1005 copolymer and these formulations were used to immunize C57BL/6 mice. The CRL1005 copolymer appeared to be more potent than either Quil-A or alum and comparable to the RAS formulation, based on the numbers of responding mice and the OVA-specific antibody titers. Alum. RAS and Quil-A all augmented the production of IgG1 and IgG2l, similarly whereas only the CFA/IFA boosted IgG2a levels significantly. The effect of adjuvants on relative antibody affinity was more variable with the CRL1005 and CFA/IFA inducing antibodies with the highest affinity scores. This high molecular weight nonionic copolymer is nontoxic in aqueous formulations and should therefore be compatible with a wide variety of protein or polysaccharide vaccine antigens.
Todd
C W
CW
Vaxcel Inc., Norcross, GA 30092, USA.
Pozzi
L A
LA
Guarnaccia
J R
JR
Balasubramanian
M
M
Henk
W G
WG
Younger
L E
LE
Newman
M J
MJ
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation; D004655:Emulsions; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D010047:Ovalbumin / Q000276:immunology*; D010316:Particle Size; D011060:Poloxalene / Q000494:pharmacology*; D015203:Reproducibility of Results; D014611:Vaccination
D000276:Adjuvants, Immunologic; D004655:Emulsions; D011060:Poloxalene; D010047:Ovalbumin