Abstract: Animals, including humans, are immunized by antigens, for example, the HA antigen of influenza, by first administering to a naive animal a normally strongly-immunogenic form of the antigen, for example, inactiviated or attenuated whole cell virus and subsequently administering a normally weakly-immunogenic isolated and purified viral antigen, to achieve an enhanced immune response to the purified viral antigen.

Abstract: Animals, including humans, are immunized by antigens, for example, the HA antigen of influenza, by first administering to a naive animal a normally strongly-immunogenic form of the antigen, for example, inactivated or attenuated whole cell virus and subsequently administering a normally weakly-immunogenic isolated and purified viral antigen, to achieve an enhanced immune response to the purified viral antigen.

Abstract: Conjugates of HA protein of influenza virus suitable for formulation as a vaccine for obtaining a strong immune response to the HA protein are formed by separating whole HA protein from the influenza virus by detergent extraction or by providing whole HA protein by recombinant procedure, treating the HA protein with hydroxylamine to form free sulfhydryl groups in the cytoplasmic domain of the protein, and cross-linking the free sulfhydryl group-containing HA protein to itself using a bis-maleimide linker or to a maleimide-modified diphtheria toxoid, tetanus toxoid or influenza NP protein or other carrier molecule. The procedure is applicable to other proteins which can be separated from a cellular material, such as a virus, and which contain thioester bonds convertible to sulfhydryl groups.