Science 302:398-399, 2003). To explore whether a natural pathway to the inductive site of the mucosa-associated lymphatic tissue could be exploited for atraumatic immunization purposes, replication-deficient viral vector vaccines were sprayed directly onto the tonsils of rhesus macaques. Tonsillar immunization with viral vector vaccines encoding simian immunodeficiency virus (SIV) antigens induced cellular and humoral immune responses. Viral RNA levels after a stringent SIV challenge were reduced, providing a level of protection similar to that observed after systemic immunization with the same vaccines. Thus, atraumatic oral spray immunization with replication-deficient vectors can overcome the epithelial barrier, deliver the vaccine antigen to the mucosa-associated lymphatic tissue, and avoid induction of tolerance, providing a novel approach to circumvent acceptability problems of syringe and needle vaccines for children and in developing countries.The first immunization studies in humans with viral vectors encoding vaccine antigens have demonstrated induction of cellular and humoral immune responses (7,20,29,30,33). Several vector vaccines based on adenoviruses or poxviruses have shown promising preclinical results and are currently at different stages of clinical development for prophylactic or therapeutic use against infectious diseases or cancer.In children, syringe and needle administration of vaccines faces acceptability problems, while in developing countries the inappropriate reuse of needles and syringes is associated with an increased risk of infection. A noninvasive oral vaccination strategy could greatly facilitate worldwide access to vaccines by, for example, enabling trained teachers to administer the vaccine. So far, only live attenuated vaccines have been used for oral vaccination in humans. The efficacy of these vaccines depends on subsequent replication and spread of the vaccines in the gastrointestinal tract. Although highly efficient, the spread of live attenuated vaccines to contact persons of the vaccinees or reversion of the vaccines to virulent forms limits the applicability of the live attenuated vaccine approach for many infectious diseases. Oral vaccination with replicationdeficient viral vector vaccines might be able to substitute for the live attenuated vaccines, but it is questionable whether they can elicit substantial immune responses given that the excess amount of antigens taken up as food on a regular basis mostly leads to tolerance rather than immunity. In addition, if only the superficial layers of the mucosa are transduced by the viral vector vaccines, shedding of the transduced cells prior to expression of the vaccine antigen could be expected.The epithelial barrier of the oral cavity to be passed by viral vector vaccines consists of a multilayer, nonkeratinized squamous epithelium. Below the epithelium, the oral cavity contains the Waldeyer's ring, an important member of the mucosaassociated lymphatic tissue (MALT), including the lingual and palatine tonsils. The crypts...

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We investigated the immunogenicity and efficacy of a bimodal prime/boost vaccine regimen given by various routes in the Simian immunodeficiency virus (SIV) rhesus monkey model for AIDS. Twelve animals were immunized with SIV DNA-vectors followed by the application of a recombinant adenovirus (rAd5) expressing the same genes either intramuscularly (i.m.) or by oropharyngeal spray. The second rAd5-application was given i.m. All vaccinees plus six controls were challenged orally with SIVmac239 12 weeks post-final immunization. Both immunization strategies induced strong SIV Gag-specific IFN-gamma and T-cell proliferation responses and mediated a conservation of CD4(+) memory T-cells and a reduction of viral load during peak viremia following infection. Interestingly, the mucosal group was superior to the systemic group regarding breadth and strength of SIV-specific T-cell responses and exhibited lower vector specific immune responses. Therefore, our data warrant the inclusion of mucosal vector application in a vaccination regimen which makes it less invasive and easier to apply.

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Approved for public release; distribution is unlimited.The combustion of gas-gas hypergolic propellants with MMH (Monomethylhydrazine) as fuel and RFNA (Red fuming nitric acid) as oxidizer are studied numerically for unlike impinging jets near an inclined wall using a detailed chemical reaction mechanism. The current study focuses on quantifying the effect of the inclined wall on the ignition characteristics: namely, contact time/location and ignition delay/location. Furthermore, the effect of wall is assessed with respect to mixing and flame spreading. The baseline threedimensional simulation results compare two domains, with and without the inclined wall, under the same inlet flow conditions. These results show that the space between the wall surface and injector tips acts as a mixing zone with intensified vorticity and heat release rate. Two-dimensional results for various injection velocities are also presented and are compared with the three-dimensional results.