INTRANASAL PRIMING WITH RECOMBINANT BORDETELLA-PERTUSSIS FOR THE INDUCTION OF A SYSTEMIC IMMUNE-RESPONSE AGAINST A HETEROLOGOUS ANTIGEN

One of the current goals in vaccine development is the noninvasive adm inistration of protective antigens via mucosal surfaces. In this conte xt, the gut-associated lymphoid tissues have already been extensively explored. Vaccination via the nasal route has only recently been the f ocus of intensive investigation, and no live vector specifically desig ned for the respiratory mucose is yet available. In this study we show that intranasal administration of the recombinant Bordetella pertussi s BPGR60, producing the Schistosoma mansoni 28-kDa glutathione S-trans ferase (Sm28GST) protective antigen fused to filamentous hemagglutinin , induces priming in mice for the production of serum antibodies. In a ddition to significant levels of anti-Sm28GST immunoglobulin A (IgA) a ntibodies, high levels of anti-Sm28GST serum antibodies were obtained after intranasal boost with the purified antigen or infection with S. mansoni following intranasal priming with BPGR60. These antibodies wer e of the IgG1, IgG2a, and IgG2b isotypes, suggesting a mixed immune re sponse. No priming was observed in animals that had received nonrecomb inant B. pertussis or purified Sm28GST, indicating specific priming by BPGR60. This priming was also evident in immune protection against S. mansoni challenge. Significant protection against worm burden and egg output was obtained in mice primed with BPGR60 and intranasally boost ed with purified Sm28GST. A lower but still significant degree of prot ection against egg output was also obtained in mice infected with a si ngle dose of BPGR60. These results indicate that intranasal administra tion of recombinant B. pertussis can prime for serum antibody response s against a foreign antigen and for heterologous protection.