Increasing the immunogenicity of a trivalent influenza virus vaccine with adjuvant-active nonionic block copolymers for potential use in the elderly.

ABSTRACT

High molecular weight nonionic block copolymers consisting of a large hydrophobic core made from repeat oxypropylene units and smaller hydrophilic blocks of oxyethylene repeat units were evaluated as adjuvants in experimental influenza virus vaccine formulations. The goal was to identify a copolymer that would increase the immunogenicity of the commercial Fluogen trivalent influenza virus vaccine. Vaccine experiments done using BALB/c mice provided data that allowed us to identify a copolymer that increased both antibody titers specific for total virus proteins as well as antibodies with hemagglutination inhibition (HAI) activity. This copolymer, termed CRL1005, increased the production of IgG1, IgG2a and IgG2b which suggested it increased the activity of both Type-1 and Type-2 T-helper lymphocytes. The CRL1005 copolymer was tested further in rhesus monkeys with similar results. Levels of antibodies specific for total virus protein preparations were increased as were HAI antibody titers following vaccination with the copolymer-supplemented Fluogen vaccine. Thus, the CRL1005 copolymer adjuvant appears to be compatible for use with the current generation of inactivated viron-based influenza vaccines and useful for increasing the immunogenicity. A more potent influenza virus vaccine could well be more efficacious in the aged segment of our population than current vaccines.