Luigi & Franco Buonaguro
e-mail: irccsvir AT unina.it
affiliation: Istituto Pascale, Napoli
research area(s): Cancer Biology, Immunity And Infection
Course:
Basic and Applied Immunology
University/Istitution: Università Vita-Salute San Raffaele
University/Istitution: Università Vita-Salute San Raffaele
Born in Sant’Agata de’ Goti (BN), Italy (1952) Dr. Franco M. Buonaguro obtained his Medical Doctor degree at the University of Naples, Italy, in 1977 (summa cum laude), where he also became Specialist in Endocrinology in 1982 (summa cum laude), Microbiology and Virology in 1992 (summa cum laude).
After a postdoctoral fellowship at the Department of Cell Biology, Argonne National Laboratory, Argonne, IL, USA (1979-81), a WHO Fellowship and research associate position at the Tumor Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA (1983-86), he became an assistant member of the Experimental Oncology F – Viral Oncology at Natl Cancer Institute in Naples. He was promoted associate member in 1991, and became full member in 2001. Since 2008 Dr F.M. Buonaguro is Director of the Molecular Biology and Viral Oncogenesis Unit of the Experimental Oncology Department at the Natl Cancer Institute “Fond Pascale “ Napoli-Italy.
Dr F.M. Buonaguro dedicated a lot of energy for Developing-Countries’ needs, in particular he has been involved in a large International Programs on AIDS Research in Uganda, one of the Countries most heavily hit by the epidemic, developing and coordinating the ICSC World Lab East Africa AIDS Research Center at the Uganda Virus Research Institute (UVRI) - Entebbe, of which he has been co-Director since 1995 and Director since April 2001. He is member of the World Federation of Scientists since 1997, has served as WHO virology consultant in 1996 and 2003. Member of WHO/ UNAIDS Network for HIV isolation and Characterization since 1996; Member WHO HPV DNA International Collaborative Study Group since 2002. With respect to editorial activities Dr F.M. Buonaguro is Editor in chief of Infectious Agents and Cancer a 2006-established online journal published by BioMed Central at www.infectagentscancer.com; Managing Editor of Frontiers in Bioscience; Editorial Board Member of Chinese Journal of Medicine [http://www.cjmed.net/]. He has authored >90 original scientific articles published in peer-reviewd journals (including Biochemistry, Nature, Carcinogenesis, Science, Nucleic Acids Research, Int J. Cancer, Brit. J of Cancer, Cancer Letters, Virology, J. Virol., AIDS, Vaccine, etc.) and of 10 reviews and book chapters, for a cumulative impact factor of 216 (since 1992).
Dr. Luigi Buonaguro received his medical degree in 1988 from the Univ. of Naples – Italy “Federico II”; in 1992 he received his Microbiology and Virology specialty degree from the same University.
After his PostDoctoral training at the Lab. of Tumor Cell Biology, Natl. Cancer Inst., Natl. Institutes of Health, Bethesda MD, USA (Director, Robert C. Gallo), he joined the Lab. of Viral Oncology at the National Cancer Institute “Fond. Pascale”, Naples – Italy, where he currently is an Associate Member of the Mol Biol and Viral Oncogenesis Unit. From 2005 he has an appointment as Adjunct Associate Professor, Univ. of Maryland School of Medicine, Infectious Diseases Division at Institute of Human Virology, Baltimore MD – USA (Director, Robert C. Gallo).
Dr. L. Buonaguro is Member of the Following Scientific Societies: Italian Society for Virology (Società Italiana di Virologia - SIV); Italian Society for Medical Virology (Società Italiana di Virologia Medica - SIVIM); American Society for Microbiology (ASM). Moreover he is External expert of the “UNAIDS Network for isolation and characterization of HIV-1”.
Dr. L. Buonaguro is Member several Journal Editorial Boards. Moreover he is Section Editor of the Immunovirology Section of the Journal of Translational Medicine and Co-Editor-in-Chief of The Open AIDS Journal. Guest Editor of the Mini Hot Topic Issue on “Novel Vaccines and Adjuvants” for Current HIV Research Journal. F1000 Medicine Faculty Member, Infectious Diseases Section: AIDS Vaccine. Ad Hoc Reviewer for AIDS, JAIDS, J Virol, J Clinical Microbiol, Clinical Vaccine Immunol.
Dr. L. Buonaguro has been Member of the Scientific Organizing Committee, “AIDS Vaccine” Conference series, organized by the Global HIV Vaccine Enterprise.
Dr. Buonaguro has published, as author and co-author, more than 70 papers in International Peer-Reviewes Journals. He has participated at more than 150 National and International Meetings and in many of these as Guest Speaker.
After a postdoctoral fellowship at the Department of Cell Biology, Argonne National Laboratory, Argonne, IL, USA (1979-81), a WHO Fellowship and research associate position at the Tumor Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA (1983-86), he became an assistant member of the Experimental Oncology F – Viral Oncology at Natl Cancer Institute in Naples. He was promoted associate member in 1991, and became full member in 2001. Since 2008 Dr F.M. Buonaguro is Director of the Molecular Biology and Viral Oncogenesis Unit of the Experimental Oncology Department at the Natl Cancer Institute “Fond Pascale “ Napoli-Italy.
Dr F.M. Buonaguro dedicated a lot of energy for Developing-Countries’ needs, in particular he has been involved in a large International Programs on AIDS Research in Uganda, one of the Countries most heavily hit by the epidemic, developing and coordinating the ICSC World Lab East Africa AIDS Research Center at the Uganda Virus Research Institute (UVRI) - Entebbe, of which he has been co-Director since 1995 and Director since April 2001. He is member of the World Federation of Scientists since 1997, has served as WHO virology consultant in 1996 and 2003. Member of WHO/ UNAIDS Network for HIV isolation and Characterization since 1996; Member WHO HPV DNA International Collaborative Study Group since 2002. With respect to editorial activities Dr F.M. Buonaguro is Editor in chief of Infectious Agents and Cancer a 2006-established online journal published by BioMed Central at www.infectagentscancer.com; Managing Editor of Frontiers in Bioscience; Editorial Board Member of Chinese Journal of Medicine [http://www.cjmed.net/]. He has authored >90 original scientific articles published in peer-reviewd journals (including Biochemistry, Nature, Carcinogenesis, Science, Nucleic Acids Research, Int J. Cancer, Brit. J of Cancer, Cancer Letters, Virology, J. Virol., AIDS, Vaccine, etc.) and of 10 reviews and book chapters, for a cumulative impact factor of 216 (since 1992).
Dr. Luigi Buonaguro received his medical degree in 1988 from the Univ. of Naples – Italy “Federico II”; in 1992 he received his Microbiology and Virology specialty degree from the same University.
After his PostDoctoral training at the Lab. of Tumor Cell Biology, Natl. Cancer Inst., Natl. Institutes of Health, Bethesda MD, USA (Director, Robert C. Gallo), he joined the Lab. of Viral Oncology at the National Cancer Institute “Fond. Pascale”, Naples – Italy, where he currently is an Associate Member of the Mol Biol and Viral Oncogenesis Unit. From 2005 he has an appointment as Adjunct Associate Professor, Univ. of Maryland School of Medicine, Infectious Diseases Division at Institute of Human Virology, Baltimore MD – USA (Director, Robert C. Gallo).
Dr. L. Buonaguro is Member of the Following Scientific Societies: Italian Society for Virology (Società Italiana di Virologia - SIV); Italian Society for Medical Virology (Società Italiana di Virologia Medica - SIVIM); American Society for Microbiology (ASM). Moreover he is External expert of the “UNAIDS Network for isolation and characterization of HIV-1”.
Dr. L. Buonaguro is Member several Journal Editorial Boards. Moreover he is Section Editor of the Immunovirology Section of the Journal of Translational Medicine and Co-Editor-in-Chief of The Open AIDS Journal. Guest Editor of the Mini Hot Topic Issue on “Novel Vaccines and Adjuvants” for Current HIV Research Journal. F1000 Medicine Faculty Member, Infectious Diseases Section: AIDS Vaccine. Ad Hoc Reviewer for AIDS, JAIDS, J Virol, J Clinical Microbiol, Clinical Vaccine Immunol.
Dr. L. Buonaguro has been Member of the Scientific Organizing Committee, “AIDS Vaccine” Conference series, organized by the Global HIV Vaccine Enterprise.
Dr. Buonaguro has published, as author and co-author, more than 70 papers in International Peer-Reviewes Journals. He has participated at more than 150 National and International Meetings and in many of these as Guest Speaker.
Virus-associated tumors account for more than 20% of all human cancers, and represent an optimal biological model to study the pathogenetic mechanisms involved in the human tumorigenesis. Moreover, the prolonged life expectancy of AIDS patients due to an effective anti-retroviral therapy is associated to a growing rate of AIDS-associated tumors in such patients.
The understanding of the molecular mechanisms involved in the pathogen-host interactions and the relevant viral/cellular proteins in the transformation process, as well as of the strategies to impact on the host immune response in order to effectively control the viral infection are pivotal to modify/block the multistep process involved in the oncogenic progression of the virus-associated tumors.
In this context, our Group has been involved in the last years in studies targeting the Human Immunodeficiency Virus (HIV), the Human Papillomavirus (HPV) and the Human Hepatitis C Virus (HCV).
In regards to HIV, our Group has been heavily involved in molecular epidemiological studies of HIV to identify the prevalent molecular/antigenic forms to be selected for design and development of preventive/therapeutic vaccine approaches. Based on these results, a HIV vaccine model based on Virus-like particles (VLPs) has been pursued in the last ten years.
The VLPs developed in our laboratory are based on the HIV-1 Pr55gag precursor protein (HIV-VLPs) and display an entire gp120/140 molecules, inducing HIV-1-specific CD4+ and CD8+T cell responses as well as cross-clade neutralizing antibodies in immunized Balb/c mice at systemic and mucosal sites.
In parallel to immunogenicity studies, in the last years we have been interested in studying the interactions between our VLPs and Antigen Presenting Cells (APC), showing that baculovirus-expressed HIV-VLPs are able to induce maturation and activation of Monocyte-Derived DCs (MDDCs) and that this effect is partially mediated by the internal TLRs 3 and 9. Moreover, the HIV-VLP-activated MDDCs show specific transcriptional profiles of genes involved in the morphological and functional changes characterizing the MDDCs activation and maturation. Similar results can be observed also in CD14+ uncultured PBMCs of HIV negative and positive individuals, greatly facilitating the screening of individual response to vaccines.
In regards to HCV, our Group has been recently involved in studies aimed to investigate the genes involved in viral carcinogenesis and tumour progression in patients with HCV and hepatocellular carcinoma (HCC). Studying the global gene expression pattern by the microarray technology, the differential gene expression between HCV correlated HCC and Healthy donor, and HCV correlated Cirrhosis and Healthy donor has been evaluated.
Class comparison analysis revealed 825 deferentially expressed genes with 3-fold difference at a significance p-value of < 0.01 between HCC samples and controls. The up-regulated genes are involved in pathways related to the Metabolism, the Aryl Hydrocarbon receptor, the protein Ubiquitination and 14-3-3 mediated signaling.
Furthermore, class comparison analysis revealed 151 deferentially expressed genes with 3-fold difference at a significance p-value of < 0.001 have been identified between HCV cirrhotic samples and controls. The up-regulated genes are involved in pathways related to the Antigen Presentation, Interferon signaling, IL-4 signaling, Bacteria and Viruses cell cycle and chemokine signaling (De Giorgi V et al., 2009).
In parallel, we are evaluating the immunotherapeutic effects of vaccine candidates in HCV-associated lymphoproliferative disorders. A limited group of subjects affected by chronic HCV infections can develop lymphoma disorders, often preceded by a cryoglobulinemia. Such HCV-associated lymphomas are characterized by neoplastic B lymphocyte clones expressing clonotypic Igs (idiotypes) which can be considered as tumor-specific antigens. In particular, the VK3-20 protein represents one the most conserved idiotypes frequently expressed in HCV-associated B-NHL. The VK3-20 is immunogenic and induces cytotoxic responses specific for VK-related proteins espressed also in other B-cell lymphoma/leukemia.
In this context, our Group is evaluating the studying the interactions between the VK3-20 protein and Antigen Presenting Cells (APC) from healthy seronegative subjects and/or HCV-infected subjects in different stages toward B-NHL. In particular, we are evaluating the expression of activation/maturation markers, cytokine pattern and whole gene transcritption profile.
The Unit directed by Dr. F.M. Buonaguro is recipient of several projects funded by Italian Public Agencies (Ministero della Salute e Ministero dell’Università e Ricerca) and is Member of the NGIN Consortium (NGIN: Next Generation HIV-1 Immunogens inducing broad Neutralizing antibodies) funded by the European Commission within the Framework Program 7.
The understanding of the molecular mechanisms involved in the pathogen-host interactions and the relevant viral/cellular proteins in the transformation process, as well as of the strategies to impact on the host immune response in order to effectively control the viral infection are pivotal to modify/block the multistep process involved in the oncogenic progression of the virus-associated tumors.
In this context, our Group has been involved in the last years in studies targeting the Human Immunodeficiency Virus (HIV), the Human Papillomavirus (HPV) and the Human Hepatitis C Virus (HCV).
In regards to HIV, our Group has been heavily involved in molecular epidemiological studies of HIV to identify the prevalent molecular/antigenic forms to be selected for design and development of preventive/therapeutic vaccine approaches. Based on these results, a HIV vaccine model based on Virus-like particles (VLPs) has been pursued in the last ten years.
The VLPs developed in our laboratory are based on the HIV-1 Pr55gag precursor protein (HIV-VLPs) and display an entire gp120/140 molecules, inducing HIV-1-specific CD4+ and CD8+T cell responses as well as cross-clade neutralizing antibodies in immunized Balb/c mice at systemic and mucosal sites.
In parallel to immunogenicity studies, in the last years we have been interested in studying the interactions between our VLPs and Antigen Presenting Cells (APC), showing that baculovirus-expressed HIV-VLPs are able to induce maturation and activation of Monocyte-Derived DCs (MDDCs) and that this effect is partially mediated by the internal TLRs 3 and 9. Moreover, the HIV-VLP-activated MDDCs show specific transcriptional profiles of genes involved in the morphological and functional changes characterizing the MDDCs activation and maturation. Similar results can be observed also in CD14+ uncultured PBMCs of HIV negative and positive individuals, greatly facilitating the screening of individual response to vaccines.
In regards to HCV, our Group has been recently involved in studies aimed to investigate the genes involved in viral carcinogenesis and tumour progression in patients with HCV and hepatocellular carcinoma (HCC). Studying the global gene expression pattern by the microarray technology, the differential gene expression between HCV correlated HCC and Healthy donor, and HCV correlated Cirrhosis and Healthy donor has been evaluated.
Class comparison analysis revealed 825 deferentially expressed genes with 3-fold difference at a significance p-value of < 0.01 between HCC samples and controls. The up-regulated genes are involved in pathways related to the Metabolism, the Aryl Hydrocarbon receptor, the protein Ubiquitination and 14-3-3 mediated signaling.
Furthermore, class comparison analysis revealed 151 deferentially expressed genes with 3-fold difference at a significance p-value of < 0.001 have been identified between HCV cirrhotic samples and controls. The up-regulated genes are involved in pathways related to the Antigen Presentation, Interferon signaling, IL-4 signaling, Bacteria and Viruses cell cycle and chemokine signaling (De Giorgi V et al., 2009).
In parallel, we are evaluating the immunotherapeutic effects of vaccine candidates in HCV-associated lymphoproliferative disorders. A limited group of subjects affected by chronic HCV infections can develop lymphoma disorders, often preceded by a cryoglobulinemia. Such HCV-associated lymphomas are characterized by neoplastic B lymphocyte clones expressing clonotypic Igs (idiotypes) which can be considered as tumor-specific antigens. In particular, the VK3-20 protein represents one the most conserved idiotypes frequently expressed in HCV-associated B-NHL. The VK3-20 is immunogenic and induces cytotoxic responses specific for VK-related proteins espressed also in other B-cell lymphoma/leukemia.
In this context, our Group is evaluating the studying the interactions between the VK3-20 protein and Antigen Presenting Cells (APC) from healthy seronegative subjects and/or HCV-infected subjects in different stages toward B-NHL. In particular, we are evaluating the expression of activation/maturation markers, cytokine pattern and whole gene transcritption profile.
The Unit directed by Dr. F.M. Buonaguro is recipient of several projects funded by Italian Public Agencies (Ministero della Salute e Ministero dell’Università e Ricerca) and is Member of the NGIN Consortium (NGIN: Next Generation HIV-1 Immunogens inducing broad Neutralizing antibodies) funded by the European Commission within the Framework Program 7.
1: Tagliamonte M, Visciano ML, Tornesello ML, De Stradis A, Buonaguro FM,
Buonaguro L. HIV-Gag VLPs presenting trimeric HIV-1 gp140 spikes constitutively
expressed in stable double transfected insect cell line. Vaccine. 2011 Jul
12;29(31):4913-22.
2: Visciano ML, Diomede L, Tagliamonte M, Tornesello ML, Asti V, Bomsel M,
Buonaguro FM, Lopalco L, Buonaguro L. Generation of HIV-1 Virus-Like Particles
expressing different HIV-1 glycoproteins. Vaccine. 2011 Jul 12;29(31):4903-12.
3: Buonaguro FM, Tornesello ML, Buonaguro L. New adjuvants in evolving vaccine
strategies. Expert Opin Biol Ther. 2011 Jul;11(7):827-32.
4: Tornesello ML, Losito S, Benincasa G, Fulciniti F, Botti G, Greggi S,
Buonaguro L, Buonaguro FM. Human papillomavirus (HPV) genotypes and HPV16
variants and risk of adenocarcinoma and squamous cell carcinoma of the cervix.
Gynecol Oncol. 2011 Apr;121(1):32-42.
5: Hemelaar J, Gouws E, Ghys PD, Osmanov S; WHO-UNAIDS Network for HIV Isolation and Characterisation. Global trends in molecular epidemiology of HIV-1 during 2000-2007. AIDS. 2011 Mar 13;25(5):679-89.
6: Tornesello ML, Buonaguro L, Cristillo M, Biryahwaho B, Downing R, Hatzakis A, Alessi E, Cusini M, Ruocco V, Viviano E, Romano N, Katongole-Mbidde E, Buonaguro FM. MDM2 and CDKN1A gene polymorphisms and risk of Kaposi's sarcoma in African and Caucasian patients. Biomarkers. 2011 Feb;16(1):42-50.
7: Tagliamonte M, Tornesello ML, Buonaguro FM, Buonaguro L. Conformational HIV-1 envelope on particulate structures: a tool for chemokine coreceptor binding
studies. J Transl Med. 2011 Jan 27;9 Suppl 1:S1.
8: Poli G, Buonaguro L. Introducing the issue on "differential use of CCR5 versus CXCR4 by HIV-1. Pathogenic, translational and clinical open questions". J Transl Med. 2011 Jan 27;9 Suppl 1:I1.
9: Buonaguro L, Petrizzo A, Tornesello ML, Buonaguro FM. Translating tumor
antigens into cancer vaccines. Clin Vaccine Immunol. 2011 Jan;18(1):23-34. Epub
2010 Nov 3.
10: Buonaguro L, Pulendran B. Immunogenomics and systems biology of vaccines.
Immunol Rev. 2011 Jan;239(1):197-208.
11: De Rossi A, Zanchetta M, Vitone F, Antonelli G, Bagnarelli P, Buonaguro L,
Capobianchi MR, Clementi M, Abbate I, Canducci F, Monachetti A, Riva E, Rozera G, Scagnolari C, Tagliamonte M, Re MC; SIVIM (Italian Society of Medical Virology) roup. Quantitative HIV-1 proviral DNA detection: a multicentre analysis. New Microbiol. 2010 Oct;33(4):293-302.
12: Tagliamonte M, Visciano ML, Tornesello ML, De Stradis A, Buonaguro FM,
Buonaguro L. Constitutive expression of HIV-VLPs in stably transfected insect
cell line for efficient delivery system. Vaccine. 2010 Sep 7;28(39):6417-24.
13: Scotti N, Buonaguro L, Tornesello ML, Cardi T, Buonaguro FM. Plant-based
anti-HIV-1 strategies: vaccine molecules and antiviral approaches. Expert Rev
Vaccines. 2010 Aug;9(8):925-36.
14: Tornesello ML, Loquercio G, Tagliamonte M, Rossano F, Buonaguro L, Buonaguro FM. Human papillomavirus infection in urine samples from male renal transplant patients. J Med Virol. 2010 Jul;82(7):1179-85.
15: Buonaguro L. Novel vaccines and adjuvants. Curr HIV Res. 2010 Jun;8(4):273.
16: Buonaguro L, Tornesello ML, Buonaguro FM. Virus-like particles as particulate vaccines. Curr HIV Res. 2010 Jun;8(4):299-309.
17: Ross AL, Bråve A, Scarlatti G, Manrique A, Buonaguro L. Progress towards
development of an HIV vaccine: report of the AIDS Vaccine 2009 Conference. Lancet Infect Dis. 2010 May;10(5):305-16.
18: Tornesello ML, Biryahwaho B, Downing R, Hatzakis A, Alessi E, Cusini M,
Ruocco V, Katongole-Mbidde E, Loquercio G, Buonaguro L, Buonaguro FM. Human
herpesvirus type 8 variants circulating in Europe, Africa and North America in
classic, endemic and epidemic Kaposi's sarcoma lesions during pre-AIDS and AIDS
era. Virology. 2010 Mar 15;398(2):280-9.
19: Buonaguro L, Petrizzo A, Tornesello M, Napolitano M, Martorelli D, Castello
G, Beneduce G, De Renzo A, Perrella O, Romagnoli L, Sousa V, De Re V, Dolcetti R, Buonaguro FM. Immune signatures in human PBMCs of idiotypic vaccine for
HCV-related lymphoproliferative disorders. J Transl Med. 2010 Feb 19;8:18.
20: De Giorgi V, Monaco A, Worchech A, Tornesello M, Izzo F, Buonaguro L,
Marincola FM, Wang E, Buonaguro FM. Gene profiling, biomarkers and pathways
characterizing HCV-related hepatocellular carcinoma. J Transl Med. 2009 Oct
12;7:85.
Buonaguro L. HIV-Gag VLPs presenting trimeric HIV-1 gp140 spikes constitutively
expressed in stable double transfected insect cell line. Vaccine. 2011 Jul
12;29(31):4913-22.
2: Visciano ML, Diomede L, Tagliamonte M, Tornesello ML, Asti V, Bomsel M,
Buonaguro FM, Lopalco L, Buonaguro L. Generation of HIV-1 Virus-Like Particles
expressing different HIV-1 glycoproteins. Vaccine. 2011 Jul 12;29(31):4903-12.
3: Buonaguro FM, Tornesello ML, Buonaguro L. New adjuvants in evolving vaccine
strategies. Expert Opin Biol Ther. 2011 Jul;11(7):827-32.
4: Tornesello ML, Losito S, Benincasa G, Fulciniti F, Botti G, Greggi S,
Buonaguro L, Buonaguro FM. Human papillomavirus (HPV) genotypes and HPV16
variants and risk of adenocarcinoma and squamous cell carcinoma of the cervix.
Gynecol Oncol. 2011 Apr;121(1):32-42.
5: Hemelaar J, Gouws E, Ghys PD, Osmanov S; WHO-UNAIDS Network for HIV Isolation and Characterisation. Global trends in molecular epidemiology of HIV-1 during 2000-2007. AIDS. 2011 Mar 13;25(5):679-89.
6: Tornesello ML, Buonaguro L, Cristillo M, Biryahwaho B, Downing R, Hatzakis A, Alessi E, Cusini M, Ruocco V, Viviano E, Romano N, Katongole-Mbidde E, Buonaguro FM. MDM2 and CDKN1A gene polymorphisms and risk of Kaposi's sarcoma in African and Caucasian patients. Biomarkers. 2011 Feb;16(1):42-50.
7: Tagliamonte M, Tornesello ML, Buonaguro FM, Buonaguro L. Conformational HIV-1 envelope on particulate structures: a tool for chemokine coreceptor binding
studies. J Transl Med. 2011 Jan 27;9 Suppl 1:S1.
8: Poli G, Buonaguro L. Introducing the issue on "differential use of CCR5 versus CXCR4 by HIV-1. Pathogenic, translational and clinical open questions". J Transl Med. 2011 Jan 27;9 Suppl 1:I1.
9: Buonaguro L, Petrizzo A, Tornesello ML, Buonaguro FM. Translating tumor
antigens into cancer vaccines. Clin Vaccine Immunol. 2011 Jan;18(1):23-34. Epub
2010 Nov 3.
10: Buonaguro L, Pulendran B. Immunogenomics and systems biology of vaccines.
Immunol Rev. 2011 Jan;239(1):197-208.
11: De Rossi A, Zanchetta M, Vitone F, Antonelli G, Bagnarelli P, Buonaguro L,
Capobianchi MR, Clementi M, Abbate I, Canducci F, Monachetti A, Riva E, Rozera G, Scagnolari C, Tagliamonte M, Re MC; SIVIM (Italian Society of Medical Virology) roup. Quantitative HIV-1 proviral DNA detection: a multicentre analysis. New Microbiol. 2010 Oct;33(4):293-302.
12: Tagliamonte M, Visciano ML, Tornesello ML, De Stradis A, Buonaguro FM,
Buonaguro L. Constitutive expression of HIV-VLPs in stably transfected insect
cell line for efficient delivery system. Vaccine. 2010 Sep 7;28(39):6417-24.
13: Scotti N, Buonaguro L, Tornesello ML, Cardi T, Buonaguro FM. Plant-based
anti-HIV-1 strategies: vaccine molecules and antiviral approaches. Expert Rev
Vaccines. 2010 Aug;9(8):925-36.
14: Tornesello ML, Loquercio G, Tagliamonte M, Rossano F, Buonaguro L, Buonaguro FM. Human papillomavirus infection in urine samples from male renal transplant patients. J Med Virol. 2010 Jul;82(7):1179-85.
15: Buonaguro L. Novel vaccines and adjuvants. Curr HIV Res. 2010 Jun;8(4):273.
16: Buonaguro L, Tornesello ML, Buonaguro FM. Virus-like particles as particulate vaccines. Curr HIV Res. 2010 Jun;8(4):299-309.
17: Ross AL, Bråve A, Scarlatti G, Manrique A, Buonaguro L. Progress towards
development of an HIV vaccine: report of the AIDS Vaccine 2009 Conference. Lancet Infect Dis. 2010 May;10(5):305-16.
18: Tornesello ML, Biryahwaho B, Downing R, Hatzakis A, Alessi E, Cusini M,
Ruocco V, Katongole-Mbidde E, Loquercio G, Buonaguro L, Buonaguro FM. Human
herpesvirus type 8 variants circulating in Europe, Africa and North America in
classic, endemic and epidemic Kaposi's sarcoma lesions during pre-AIDS and AIDS
era. Virology. 2010 Mar 15;398(2):280-9.
19: Buonaguro L, Petrizzo A, Tornesello M, Napolitano M, Martorelli D, Castello
G, Beneduce G, De Renzo A, Perrella O, Romagnoli L, Sousa V, De Re V, Dolcetti R, Buonaguro FM. Immune signatures in human PBMCs of idiotypic vaccine for
HCV-related lymphoproliferative disorders. J Transl Med. 2010 Feb 19;8:18.
20: De Giorgi V, Monaco A, Worchech A, Tornesello M, Izzo F, Buonaguro L,
Marincola FM, Wang E, Buonaguro FM. Gene profiling, biomarkers and pathways
characterizing HCV-related hepatocellular carcinoma. J Transl Med. 2009 Oct
12;7:85.
Project Title:
Project Title:
Development and/or immunogenic characterization in vivo and ex vivo of antigens specific for HCV and HCV-associated disorders
In the context of the studies currently ongoing in the Unit, the project aims to develop and/or to evaluate new antigens, delivery/presentation systems, antigen/adjuvant combinations targeting HCV (for which no vaccine is yet available to now) or HCV-associated disorders (i.e.: lymphomas). Molecules developed by the Unit or made available to the Unit by collaborating Groups (i.e.: Biotech Companies) will be evaluated in vivo for their immunogenicity in small animal models and ex vivo for their interaction with Antigen Presenting Cells (APC) from human subjects. The in vivo immunogenicity will be assessed evaluating the titer of specific antibodies as well as the CD4+ and CD8+ T-cell response against specific immunizing epitopes by Lymphoproliferation assay (LPA), Intracellular cytokine staining (ICS) and IFN- ELISPOT assay. The ex vivo study on APCs from human subjects will evaluate 1) the expression of maturation markers and co-stimulatory molecules as well as production of Th1/Th2 polarizing cytokines; 2) the ability of loaded APCs to activate ex vivo autologous naïve CD4+ T cells and to drive them toward a Th1 polarization; 3) the predicting parameters of responsiveness to vaccine; 4) the global pattern of gene expression in activated DCs, to identify key pathways involved in cellular functions induced by vaccine activation and relevant for guiding modifications/optimizations of the vaccination strategy.
Project Title:
Development and/or immunogenic characterization in vivo and ex vivo of antigens specific for HIV.
A prophylactic vaccine represents the ultimate strategy for blocking the HIV transmission in the general population. Among the different possible vaccine strategies currently explored by several groups, particulate structures (i.e.: VLPs, virosomes) are pursued in our Unit. Different HIV envelope glycoproteins presenting broadly neutralizing epitopes will be developed and delivered with different systems, in different adjuvanting combinations and will be evaluated in vivo for their immunogenicity in small animal models aswell as ex vivo for their interaction with Antigen Presenting Cells (APC) from human subjects.
The in vivo immunogenicity will be assessed evaluating the titer and/or breath of neutralizing antibodies induced in mice will be evaluated by ex vivo virus neutralization assay against heterologous primary HIV-1 field isolates. In parallel, the CD4+ and CD8+ T-cell response against specific HIV immunizing epitopes by Lymphoproliferation assay (LPA), Intracellular cytokine staining (ICS) and IFN- ELISPOT assay. The ex vivo study on APCs from human subjects will evaluate 1) the expression of maturation markers and co-stimulatory molecules as well as production of Th1/Th2 polarizing cytokines; 2) the ability of loaded APCs to activate ex vivo autologous naïve CD4+ T cells and to drive them toward a Th1 polarization; 3) the predicting parameters of responsiveness to vaccine; 4) the global pattern of gene expression in activated DCs, to identify key pathways involved in cellular functions induced by vaccine activation and relevant for guiding modifications/optimizations of the vaccination strategy
The in vivo immunogenicity will be assessed evaluating the titer and/or breath of neutralizing antibodies induced in mice will be evaluated by ex vivo virus neutralization assay against heterologous primary HIV-1 field isolates. In parallel, the CD4+ and CD8+ T-cell response against specific HIV immunizing epitopes by Lymphoproliferation assay (LPA), Intracellular cytokine staining (ICS) and IFN- ELISPOT assay. The ex vivo study on APCs from human subjects will evaluate 1) the expression of maturation markers and co-stimulatory molecules as well as production of Th1/Th2 polarizing cytokines; 2) the ability of loaded APCs to activate ex vivo autologous naïve CD4+ T cells and to drive them toward a Th1 polarization; 3) the predicting parameters of responsiveness to vaccine; 4) the global pattern of gene expression in activated DCs, to identify key pathways involved in cellular functions induced by vaccine activation and relevant for guiding modifications/optimizations of the vaccination strategy