EFFECTS OF THE NATURE OF ADJUVANT AND SITE OF PARENTERAL IMMUNIZATIONON THE SERUM AND MUCOSAL IMMUNE-RESPONSES INDUCED BY A NASAL BOOST WITH A VACCINE ALONE

Outbred OF1 mice were immunized subcutaneously with flu vaccine, eithe r in the neck or in the lumbar region (back), in combination with adju vants inducing either a Th1- or a Th2-type response, referred to as ad juvants Al and A2, respectively. After two parenteral immunizations, t he mice were boosted intranasally with nonadjuvanted vaccine. The seru m response was analyzed after each immunization by measuring specific immunoglobulin A: (IgA); IgG1, and;IgG2a antibody levels, while the lo cal response (same isotypes) was measured in the salivary glands after the mucosal boost by ELISPOTs, We observed that systemic priming at a ny of the two sites with a Th2 rather than a Th1 adjuvant dramatically enhanced the mucosal IgG1 and IgA responses following a mucosal boost with unadjuvanted vaccine. In addition, as judged by the IgG2a/IgG1 r atios and serum IgA levels, immunization of mice in the back induced a rise in Th2 response compared to neck immunization with adjuvant Al, In contrast, such back immunization with adjuvant A2 reversed the Th1- Th2 balance in favor of the Th1 response compared to neck immunization . Similar differences were observed in mucosal antibody levels accordi ng to the site of priming with one given adjuvant; priming in the back with adjuvant Al increased the mucosal IgA and IgG1 responses compare d to neck priming, while the local IgG2a levels were decreased. The re verse was true for adjuvant A2, Back versus neck priming with this lat ter adjuvant decreased the mucosal IgG1 response, while local IgG2a le vels were increased, The different lymphatic drainages of the two site s of parenteral immunization may explain these differences, due to the targeting of particular lymphoid inductive sites, Some of these sites may represent crossroads between systemic and mucosal immunity.