Forwarding promising vaccines for biodefense and emerging diseases into humans is often compromised by the lack of suitable adjuvants, particularly for mucosal delivery. Alternative vaccine platforms that reduce the need for adjuvants or that can be combined with novel adjuvants can address this need. We have recently developed a vaccine platform that permits increased binding to the mucosal epithelium. When fused to ourtest antigen, the ft-trefoil domain of botulinum neurotoxin serotype A (BoNT/A;also a novel vaccine candidate) which contains the protective epitopes in the cellular binding domain of BoNT heavy chain, we obtained improved secretory IgA (S-lgA) and quicker plasma IgG anti-BoNT/A antibodies (Abs) following nasal administration. Both plasma and mucosal Abs are protective against BoNT/A intoxication. Moreover, when administered parenterally, elevated plasma IgG titers are obtained. In addition, we have identified two novel adjuvants for nasally-administered vaccines that do not rely on bacterial toxins. The combined efforts will forward these new technologies to devise a vaccine regimen that will determine optimal routes of immunization with these new adjuvants. For our proposed studies, we will continue to use our vaccineprototypes for BoNT since we have the expertise in place to conduct the immunization and challenges studies. Conventional vaccines for BoNT remains problematic since only a BoNT pentavalent (A-E) vaccine is available as an investigational new drug from the CDC. This vaccine is a toxoid-based vaccine requiring multiple immunizations to induce protection. For this effort, we will develop the novel BoNT immunogens containing the (i-trefoil domain of BoNT B and E to induce protective anti-BoNT plasma IgG and mucosal IgA Abs.
In Specific Aim One, mucosa! and parenteral fe-trefoil vaccines for BoNT/B and BoNT/E will be developed building on our successful experience with BoNT/A U-trefoil;
in Specific Aim Two, novel nasal vaccine adjuvants will be tested for their ability to augment the induction of protective BoNT immunity. Our novel nasal vaccine adjuvants and vaccine formulations will be tested for their ability to augment the induction of anti-BoNT protective immunity can eventually be developed into a multivalent vaccineencompassing BoNT serotypes. In the end, we will have developed a vaccine platform capable of delivering vaccines of interest, devised new formulations with novel adjuvants, and novel vaccines for biodefense
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