SYSTEMIC CYTOKINE PROFILES IN BALB C MICE IMMUNIZED WITH TRIVALENT INFLUENZA VACCINE CONTAINING MF59 OIL EMULSION AND OTHER ADVANCED ADJUVANTS/

We have studied serum cytokine profiles in BALB/c mice after immunizat ion with influenza vaccine alone or combined with the following adjuva nts: alum; MF59 emulsion; MF59 containing the muramyl peptide 2-dipalm itoyl-sn-glycero-3-(hydroxyphosphoryloxy)) ethylamide (MTP-PE); MF59 p lus the lipid A analogue monophosphoryl lipid A; MF59 plus the Quil A saponin fraction LTC; or LTC alone. Pooled mouse sera were analyzed by ELISA at various times after immunization for IL-1 alpha, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IFN-gamma, and TNF-alpha. in naive mice, vac cine alone induced low levels of IL-3 and IL-5 only; vaccine plus alum induced a low IL-6 response as well. The MF59-based adjuvants signifi cantly increased the IL-5 and IL-6 levels, whereas Quil A LTC induced strong IFN-gamma and measurable IL-2 responses, in addition to moderat e IL-5 and IL-6. In previously infected mice, MF59 and MF59/MTP-PE wer e capable of generating IFN-gamma responses, as well as IL-5 and IL-6. All of the cytokine responses were rapid (peaking 3 to 12 h postimmun ization) and short lived. In naive mice, the MF59 adjuvants induced se rum cytokine profiles that are consistent with a primarily Th2-type re sponse, whereas the Quil A LTC induced cytokines associated with both Th1 and Th2 responses. Ab analyses indicated that, although the adjuva nts strongly affected the magnitude of the humoral response, there was no obvious correlation between the cytokine profile observed and the subclasses of Ab induced.