A novel influenza subunit vaccine composed of liposome-encapsulated haemagglutinin/neuraminidase and IL-2 or GM-CSF. II. Induction of TH1 and TH2 responses in mice

This study was aimed at analyzing, in parallel, the humoral and cellular immune responses elicited in mice immunized with liposomal influenza A (Shangdong/9/93) subunit vaccines composed of haemagglutinin/neuraminidase (H3N2) and IL-2 or GM-CSF. Recently, we reported that such vaccines evoke a more rapid, stronger and longer-lasting (over 1 year) humoral response, as well as protective immunity against viral infection, following a single administration, as compared with the response induced by the free antigen given alone or together with soluble cytokines. In the present study, BALB/C mice were immunized once, i.p., s.c., i.m. or i.n., with nonliposomal or liposomal vaccines and the humoral (antibody titer and isotypes) and cellular (DTH, cytotoxicity, cytokine production) responses were assessed at various times (2-56 weeks). The main findings were: (a) the combined liposomal vaccines consisting of encapsulated antigen and encapsulated cytokine, but not the free antigen, elicited a high titer of serum IgG1, IgG2a, IgG3 and IgM antibodies; (b) the combined liposomal vaccines were efficient following administration by the various routes, and induced a local (in lung) IgA response in i.n. vaccinated mice; (c) the liposomal vaccines triggered DTH and cytotoxic responses, as well as cytokine (mainly IL-4) production. Together, these and other findings indicate that our cytokine-supported liposomal influenza vaccines efficiently stimulate both Th1 and Th2 responses and that such vaccines may be more potent in high-risk groups than the currently used subunit vaccines.