Vaccines-2013 - OMICS Group

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Rajesh Kumar Sharma, J Vaccines Vaccin 2013, 4:5http://dx.doi.org/10.4172/2157-7560.S1.0163 rd International Conference onVaccines & VaccinationJuly 29-31, 2013 Embassy Suites Las Vegas, NV, USAA novel form of 4-1BB ligand as a potent and safe adjuvant for development of therapeuticcancer vaccinesRajesh Kumar SharmaUniversity of Louisville, USASubunit cancer vaccine represents an attractive treatment option due to tumor specificity, ability to generate memory, andsafety. However, they require potent adjuvants for therapeutic efficacy due to weak immunogenicity of TAAs and potentialself-tolerance. Given costimulation is intrinsically evolved to augment antigen specific T cell responses required for antitumorimmunity, we tested if a costimulatory molecule 4-1BBL can serve as an effective adjuvant component of the TAA based vaccineformulations. To achieve this goal, we used ProtEx for generation of chimeric SA-4-1BBL that exist as stable tetramers and higherstructures, and as such can be used as soluble proteins to effectively crosslink 4-1BB receptor on immune cells for potent signaltransduction. We herein describe a novel vaccine approach based on the use of this novel SA-4-1BBL protein as adjuvant withvarious TAAs in several cancer immunotherapy mouse models. One vaccination with the E7 or survivin with SA-4-1BBL resultedin the eradication of existing E7 expressing cervical and survivin over expressing 3LL lung tumors in >70% of the animals. Thisefficacy was improved to 100% when multiple vaccinations were used. Importantly, animals with successful immunotherapydeveloped a robust CTL responses and NK cell cytotoxicity against the tumor and long-term immune memory which was tumorantigen specific. Vaccine was well tolerated and showed no sign of overt toxicity or autoimmunity. Chimeric SA-4-1BBL has thepotential to serve as a specific immunological adjuvant to develop T cell based therapeutic vaccines against tumors with wellcharacterized tumor associated antigens.BiographyRajesh Kumar Sharma is a Faculty of Department of Medicine at University of Louisville, Louisville, KY. He completed his Ph.D. in the area ofinfectious immunology at Banaras Hindu University in India. He then moved to USA to pursue his postdoctoral studies in the area of cancerimmunology/immunotherapy and therapeutic cancer vaccines at the Institute for Cellular Therapeutics, at University of Louisville. Dr. Sharma servesas Editorial Board member and reviewer for various journals. His research interests are in the area of cancer immunology & immunotherapies,particularly development of combinatorial approaches such as chemo-immunotherapy. He has widely published in journals of Immunology, andCancer Research.rkshar01@louisville.eduJ Vaccines Vaccin 2013ISSN: 2157-7560, JVV an open access journalVaccines-2013July 29-31, 2013Volume 4 Issue 5Page 54
A. Bennett Jenson et al., J Vaccines Vaccin 2013, 4:5http://dx.doi.org/10.4172/2157-7560.S1.0163 rd International Conference onVaccines & VaccinationJuly 29-31, 2013 Embassy Suites Las Vegas, NV, USACorrect L1 initiation codon generates immunologically reactive virus-like particles of anovel laboratory mouse papillomavirus (MusPV)A. Bennett Jenson, Joongho Joh and Shin-je GhimUniversity of Louisville, USACorrectly assembled virus-like particles (VLPs) of papillomavirus (PV) display conformationally-dependent epitopes thatare type-specific, maintained on authenic virions and induce neutralizing antibodies. Alignment of the L1 amino acid (aa)sequences of 84 PVs revealed that the lengths of their N-termini are diverse and multiple possible initiation methionine (met)codons exist. The L1 gene of MusPV, that naturally infects immunodeficient laboratory mouse strain (NMRI-Foxn1nu/Foxn1nu),has 4 met codons at 1 st , 2 nd , 28 th and 30 th aa from its N-terminus. Of these, the 3 rd and 4 th mets, that are at 28 th and 30 th aa positionfrom the N-termius, respectively, are located at the position where most PVs have their start codon. These two mets, located 9 thand 11 th from the YLPP conserved aas of most PVs, should be considered as consensus initiation codons of PV L1s. Three L1proteins of MusPV starting from 2 nd , 3 rd and 4 th mets expressed using baculovirus expression system were characterized for theirability to self-assemble into VLPs. While MusPV L1 proteins starting from 2 nd met expressed a L1 protein that rarely folded intoVLPs, the L1s starting from 3 rd and 4 th mets generated correct VLPs in abundant quantities. We now conclude that the highestquantity and best quality VLPs are made from the consensus L1 met of all known PVs.BiographyA. Bennett Jenson is a Board-Certifi ed human pathologist with expertise in animal models of human disease (Distinguished Professor Lectureship11 th Annual Pathology of Mouse Models of Human Disease, September 2012). He has worked with murine leukemia virus infection of NZB/NZWmice as a model for lupus erythematosus (Scripps Clinic and Research Foundation, CA), murine animal models for virus-induced diabetes mellitus(National Institutes of Health), and animal models for human papillomavirus induced cervical, anogenital other than cervical, and head and neckcancers at Georgetown University Medical Center (Washington DC) and University of Louisville Health Science Center (Louisville, Ky). Presently heis a Professor of Vaccinology at James Graham Cancer Center, where he is working on recombinant tobacco plant papillomavirus vaccines. He haspublished over 160 peer-reviewed articles, and 40 chapters and books.abjenson@yahoo.comJ Vaccines Vaccin 2013ISSN: 2157-7560, JVV an open access journalVaccines-2013July 29-31, 2013Volume 4 Issue 5Page 55
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