?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F8052%2F&rft.title=INDUCTION+OF+STRONG+CELLULAR+IMMUNE+RESPONSES+IN+THE+GUT+MUCOSA+AGAINST+HIV-1+USING+A+COMBINATION+VACCINE+OF+RECOMBINANT+CLOSTRIDIUM+PERFRINGENS+AND+HIV-1+VIRUS+LIKE+PARTICLES&rft.creator=Poonam%2C+Poonam&rft.description=The+gut+mucosa+is+an+important+portal+for+HIV-1+transmission+and+infection.+Therefore%2C+a+vaccine+which+can+prevent+virus+transmission+at+mucosal+surfaces+would+be+an+ideal+HIV-1+vaccine+candidate.+Clostridium+perfringens+has+been+used+as+a+vehicle+to+deliver+SIV+proteins+in+large+quantity+to+the+terminal+ileum.+A+mucosal+immunization+strategy+using+C.+perfringens+should+be+able+to+induce+potent+mucosal+immune+responses+against+HIV-1.+A+recombinant+C.+perfringens+expressing+large+amount+of+HIV-1+Gag+protein+(Cp-Gag)+was+constructed.+Under+in+vitro+conditions%2C+Cp-Gag+was+found+to+induce+bone+marrow+derived+dendrite+cell+(BMDC)+to+mature+and+stimulate+HIV-1+Gag+specific+T+cell+responses.+Then+in+vivo+experiments+were+performed+in+mice+to+demonstrate+orally+delivered+Cp-Gag+ability+to+prime+gut+mucosal+T+cell+responses.+Since+oral+tolerance+is+a+major+obstacle+for+orally+delivered+immunization+approaches%2C+a+combination+of+mutated+heat-labile+enterotoxin+of+E.+coli+(mLT)+and+CpG+containing+oligodeoxynucleotides+(CpG-ODN)+were+used+as+adjuvants+for+oral+administration+with+Cp-Gag.+Orally+delivered+Cp-Gag+was+tested+for+induction+of+HIV-1+Gag+specific+T+cell+responses+in+a+prime-boost+model+with+intranasal+inoculation+of+HIV-1+virus+like+particles+(VLP).+HIV-1+specific+cellular+immune+responses+in+both+the+effector+(Lamina+propria)+and+inductive+sites+(Peyer's+patches)+of+the+gastrointestinal+(GI)+tract+were+significantly+higher+in+mice+immunized+using+Cp-Gag+and+VLPs+in+prime-boost+approaches+compared+to+mice+immunized+with+either+Cp-Gag+or+VLPs+alone.+Such+cellular+immune+response+was+found+to+be+mediated+by+both+CD8%2B+and+CD4%2B+T+cells.+These+groups+of+mice+also+seemed+to+have+HIV-1+specific+multifunctional+T+cells+in+PPs+and+LP+of+the+GI+tract.+In+summary%2C+mucosal+immunization+of+mice+with+a+Cp-Gag+and+VLPs+in+a+prime-boost+mode+led+to+strong+HIV-1+Gag+specific+cellular+immune+responses+in+both+mucosal+and+systemic+immune+compartments.+Such+strong+mucosal+immune+response+could+be+very+important+to+control+HIV-1+infection+at+mucosal+surfaces.+The+proposed+vaccine+strategy+has+great+public+health+significance+for+developing+a+practical+vaccine+against+HIV+due+to+its+safety%2C+low+production+cost+and+easy+administration.&rft.date=2009-09-28&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F8052%2F1%2FPoonamDessertation.06.15.2009.pdf&rft.identifier=++Poonam%2C+Poonam++(2009)+INDUCTION+OF+STRONG+CELLULAR+IMMUNE+RESPONSES+IN+THE+GUT+MUCOSA+AGAINST+HIV-1+USING+A+COMBINATION+VACCINE+OF+RECOMBINANT+CLOSTRIDIUM+PERFRINGENS+AND+HIV-1+VIRUS+LIKE+PARTICLES.++Doctoral+Dissertation%2C+University+of+Pittsburgh.++++(Unpublished)++