Vaccines-2013 - OMICS Group

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Nikolai Petrovsky, 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, USAStrategies for generation of broadly cross-neutralising anti-influenza vaccine responsesNikolai PetrovskyFlinders Medical Centre and Vaxine Pty Ltd., AustraliaIncreasing evidence points to the importance of broadly cross-neutralizing anti-influenza responses in providing protectionagainst pandemic strains but current seasonal influenza vaccines are poorly effective at generating such responses. Ourgroup has been exploring techniques to enhance broadly cross-neutralizing anti-influenza responses that involve use of novelrecombinant influenza antigens adjuvants (FluBlok TM , Protein Sciences Corporation) together with novel adjuvant technology(Advax TM , Vaxine Pty Ltd). This novel approach has already been advanced to the clinic and has shown promising results in itsability to modulate both anti-influenza B- and T-cell responses, in the process inducing changes in plasmablast and memoryB-cell frequency, immunoglobulin subtype and B-cell receptor usage. The significance of these changes is still being explored inanimal challenge models, but suggests that these new approaches to influenza vaccine design may one day enable production of auniversal influenza vaccine that no longer needs to be administered on an annual basis to at risk individuals. Such vaccines couldbe major life savers in the event of a future pandemic involving H5N1, H7N9 or some other new serotype of avian influenza.BiographyNikolai Petrovsky MBBS, FRACP, Ph.D. is an active hospital clinician, research professor at Flinders Medical Centre, Adelaide Australia andresearch director of Vaxine, an Australian vaccine development company. He is Secretary-General of the International Immunomics Society andhas received major funding from the US National Institutes of Health to develop novel biodefense vaccines and adjuvants. He has won prestigiousawards including the AMP Innovation Award at the 2009 Telstra Business Awards and an Ernst & Young Entrepreneur of the Year in 2010. He hastaken four vaccines to the clinic and has authored over 100 scientifi c papers and book chapters.nikolai.petrovsky@flinders.edu.auJ Vaccines Vaccin 2013ISSN: 2157-7560, JVV an open access journalVaccines-2013July 29-31, 2013Volume 4 Issue 5Page 44
Hong Xin, 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, USANew strategies to present an anti-candidiasis synthetic glycopeptide vaccine acceptable forhuman useHong Xin, Jonathan Cartmell, David R. Bundle and Jim E. CutlerLSUHSC & Children's Hospital Research Institute, USABackground: Our research on pathogenesis of experimental disseminated candidiasis led to the discovery that antibodies specificfor Candida albicans cell surface β-1, 2-mannotriose [b-(Man)3] protect mice against the disease. Use of a 14 mer peptide Fba,which derived from the N-terminal portion of the C. albicans cell surface protein fructose-bisphosphate aldolase, as the carrierfor the glycan has resulted in a novel synthetic glycopeptide vaccine b-(Man)3-Fba. This conjugate uniquely induces protectiveresponses against both the glycan and peptide carrier parts of the vaccine in a mouse model of human disseminated candidiasis.Current work: We have isolated monoclonal antibodies (MAbs) specific for the Fba peptide. Use of these MAbs in flow cytometricand confocal microscopic analyses provide evidence that the peptide is expressed on the fungal cell surface during growth as yeastand hyphal forms. Furthermore, one of the MAbs given passively to naïve mice protects the animals against candidiasis. Weconclude that the b-(Man)3-Fba vaccine protects mice by inducing protective antibodies against both the glycan and peptideparts of the vaccine conjugate. We have now modified the b-(Man)3-Fba conjugate by coupling it to tetanus toxoid (TT) in orderto improve immunogenicity and allow for use of an adjuvant suitable for human use. b-(Man)3-Fba-TT was administered alone,or as either a mixture made with alum or monophosphoryl lipid A (MPL) adjuvants by subcutaneous (s.c.) injection in miceon days 1, 21 and 62. Mice that received the conjugate vaccine prepared in either adjuvant responded as expected by makingrobust antibody responses. Surprisingly, mice that received the b-(Man)3-Fba-TT without adjuvant also responded well. All threegroups of mice also showed protection against a lethal challenge with C. albicans as evidenced by increased median survival timesand reduced kidney fungal burden as compared to control groups that received only adjuvants or DPBS buffer prior to challenge.To confirm that induced antibodies were protective, sera from mice immunized against the b-(Man)3-Fba-TT conjugate werefound to transfer protection against disseminated candidiasis to naïve mice, whereas C. albicans-adsorbed immune sera did not.Conclusion: We conclude that tetanus toxiod is a suitable secondary carrier for the glycopeptide conjugate as it induces robustantibody responses and protective immunity administered with or without adjuvants that may be suitable for human use.hxin@chnola-research.orgJ Vaccines Vaccin 2013ISSN: 2157-7560, JVV an open access journalVaccines-2013July 29-31, 2013Volume 4 Issue 5Page 45
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