DNA–VLP prime–boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity
Abstract The immune response to HIV-1 virus-like particles (VLPs), presenting a clade A Ugandan gp120, has been evaluated in a mouse model by intra-nasal (i.n.) administration by a VLP + VLP homologous or a DNA + VLP heterologous prime–boost immunization protocol, including a HIV-1 DNA gp160/rev pla...
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description | Abstract The immune response to HIV-1 virus-like particles (VLPs), presenting a clade A Ugandan gp120, has been evaluated in a mouse model by intra-nasal (i.n.) administration by a VLP + VLP homologous or a DNA + VLP heterologous prime–boost immunization protocol, including a HIV-1 DNA gp160/rev plasmid. Furthermore, the effect of the Eurocine lipid-based mucosal L3 adjuvant on the VLP immunogenicity has been assessed as well. The designed heterologous protocol is able to increase the env-specific humoral and cellular immune response, compared to the homologous protocol, which is to some extent increased by the administration of L3-adjuvanted VLP boosting dose. The anti-gag response is statistically increased in both homologous and heterologous protocols, particularly when the VLP boosting dose is adjuvanted. Immune sera from immunized animals exhibit >50% ex vivo neutralizing activity against heterologous A and B-clade viral isolates. An envelope B-cell epitope mapping shows an enhanced response against V3 epitopes all across the C2–V5 region in the heterologous prime–boost immunization strategy. The induction of humoral immunity at mucosal sites, which represents the main port of entry for the HIV-1 infection, is extremely relevant. In this framework, the DNA–VLP heterologous prime–boost protocol appears a promising preventive vaccine approach which can significantly benefit from specific mucosal adjuvants, as the Eurocine L3. |
doi_str_mv | 10.1016/j.vaccine.2007.05.052 |
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Furthermore, the effect of the Eurocine lipid-based mucosal L3 adjuvant on the VLP immunogenicity has been assessed as well. The designed heterologous protocol is able to increase the env-specific humoral and cellular immune response, compared to the homologous protocol, which is to some extent increased by the administration of L3-adjuvanted VLP boosting dose. The anti-gag response is statistically increased in both homologous and heterologous protocols, particularly when the VLP boosting dose is adjuvanted. Immune sera from immunized animals exhibit >50% ex vivo neutralizing activity against heterologous A and B-clade viral isolates. An envelope B-cell epitope mapping shows an enhanced response against V3 epitopes all across the C2–V5 region in the heterologous prime–boost immunization strategy. The induction of humoral immunity at mucosal sites, which represents the main port of entry for the HIV-1 infection, is extremely relevant. In this framework, the DNA–VLP heterologous prime–boost protocol appears a promising preventive vaccine approach which can significantly benefit from specific mucosal adjuvants, as the Eurocine L3.</description><identifier>ISSN: 0264-410X</identifier><identifier>ISSN: 1873-2518</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2007.05.052</identifier><identifier>PMID: 17629365</identifier><identifier>CODEN: VACCDE</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Acquired immune deficiency syndrome ; Administration, Intranasal ; AIDS ; AIDS Vaccines - administration & dosage ; AIDS Vaccines - immunology ; Allergy and Immunology ; Animals ; Antigens ; Applied microbiology ; Biological and medical sciences ; Deoxyribonucleic acid ; DNA ; Epitope Mapping ; Epitopes, B-Lymphocyte - immunology ; Female ; Fundamental and applied biological sciences. Psychology ; HIV Antibodies - blood ; HIV Antibodies - immunology ; HIV Envelope Protein gp160 - immunology ; HIV-1 ; HIV-1 - classification ; HIV-1 - immunology ; Human immunodeficiency virus 1 ; Humoral immunity ; Immune response ; Immune system ; Immunity, Cellular - immunology ; Immunity, Mucosal - immunology ; Immunization ; Immunization, Secondary ; Immunogenicity ; Immunoglobulin G - blood ; Infections ; Laboratories ; Lymph Nodes - cytology ; Lymph Nodes - immunology ; MEDICIN ; MEDICINE ; Mice ; Microbiology ; Miscellaneous ; Mucosal adjuvants ; Mucosal response ; Prime–boost approach ; Proteins ; Spleen - cytology ; Spleen - immunology ; Vaccines ; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) ; Vaccines, DNA - administration & dosage ; Vaccines, DNA - immunology ; Viral infections ; Virology ; Virus-like particles (VLP)</subject><ispartof>Vaccine, 2007-08, Vol.25 (32), p.5968-5977</ispartof><rights>Elsevier Ltd</rights><rights>2007 Elsevier Ltd</rights><rights>2007 INIST-CNRS</rights><rights>Copyright Elsevier Limited Aug 10, 2007</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c629t-af68593b68670b33f652e93d276f53cd3119bc45e8a49ed75ebd1df0d9d935903</citedby><cites>FETCH-LOGICAL-c629t-af68593b68670b33f652e93d276f53cd3119bc45e8a49ed75ebd1df0d9d935903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0264410X07006354$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,550,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18949516$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17629365$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-38564$$DView record from Swedish Publication Index$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:115758827$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Buonaguro, L</creatorcontrib><creatorcontrib>Devito, C</creatorcontrib><creatorcontrib>Tornesello, M.L</creatorcontrib><creatorcontrib>Schröder, U</creatorcontrib><creatorcontrib>Wahren, B</creatorcontrib><creatorcontrib>Hinkula, J</creatorcontrib><creatorcontrib>Buonaguro, F.M</creatorcontrib><title>DNA–VLP prime–boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>Abstract The immune response to HIV-1 virus-like particles (VLPs), presenting a clade A Ugandan gp120, has been evaluated in a mouse model by intra-nasal (i.n.) administration by a VLP + VLP homologous or a DNA + VLP heterologous prime–boost immunization protocol, including a HIV-1 DNA gp160/rev plasmid. Furthermore, the effect of the Eurocine lipid-based mucosal L3 adjuvant on the VLP immunogenicity has been assessed as well. The designed heterologous protocol is able to increase the env-specific humoral and cellular immune response, compared to the homologous protocol, which is to some extent increased by the administration of L3-adjuvanted VLP boosting dose. The anti-gag response is statistically increased in both homologous and heterologous protocols, particularly when the VLP boosting dose is adjuvanted. Immune sera from immunized animals exhibit >50% ex vivo neutralizing activity against heterologous A and B-clade viral isolates. An envelope B-cell epitope mapping shows an enhanced response against V3 epitopes all across the C2–V5 region in the heterologous prime–boost immunization strategy. The induction of humoral immunity at mucosal sites, which represents the main port of entry for the HIV-1 infection, is extremely relevant. In this framework, the DNA–VLP heterologous prime–boost protocol appears a promising preventive vaccine approach which can significantly benefit from specific mucosal adjuvants, as the Eurocine L3.</description><subject>Acquired immune deficiency syndrome</subject><subject>Administration, Intranasal</subject><subject>AIDS</subject><subject>AIDS Vaccines - administration & dosage</subject><subject>AIDS Vaccines - immunology</subject><subject>Allergy and Immunology</subject><subject>Animals</subject><subject>Antigens</subject><subject>Applied microbiology</subject><subject>Biological and medical sciences</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Epitope Mapping</subject><subject>Epitopes, B-Lymphocyte - immunology</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>HIV Antibodies - blood</subject><subject>HIV Antibodies - immunology</subject><subject>HIV Envelope Protein gp160 - immunology</subject><subject>HIV-1</subject><subject>HIV-1 - classification</subject><subject>HIV-1 - immunology</subject><subject>Human immunodeficiency virus 1</subject><subject>Humoral immunity</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunity, Cellular - immunology</subject><subject>Immunity, Mucosal - immunology</subject><subject>Immunization</subject><subject>Immunization, Secondary</subject><subject>Immunogenicity</subject><subject>Immunoglobulin G - blood</subject><subject>Infections</subject><subject>Laboratories</subject><subject>Lymph Nodes - cytology</subject><subject>Lymph Nodes - immunology</subject><subject>MEDICIN</subject><subject>MEDICINE</subject><subject>Mice</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>Mucosal adjuvants</subject><subject>Mucosal response</subject><subject>Prime–boost approach</subject><subject>Proteins</subject><subject>Spleen - cytology</subject><subject>Spleen - immunology</subject><subject>Vaccines</subject><subject>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)</subject><subject>Vaccines, DNA - administration & dosage</subject><subject>Vaccines, DNA - immunology</subject><subject>Viral infections</subject><subject>Virology</subject><subject>Virus-like particles (VLP)</subject><issn>0264-410X</issn><issn>1873-2518</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><sourceid>D8T</sourceid><recordid>eNqFkt-K1DAUxoso7rj6CEpB9MqO-dOkzY0y7Kq7MKigDt6FNDndzWybjkk7y-yV7-C1L-eTmM4MDizIQiAh-eXLOV--JHmK0RQjzF8vp2ultXUwJQgVU8TiIPeSCS4LmhGGy_vJBBGeZzlG34-SRyEsEUKMYvEwOcIFJ4JyNkl-n36c_fn5azH_nK68bSGuq64LfWpd71XmVFBNatt2cPZG9bZz8cAMGkKqoWmGRvlUOZNeDm3nI6lcb7Oz80WG07AJPbRWb8_bQXcHpX6TXtv-MtW-CyHTjTKQOhjig429se4iVbq364g9Th7UqgnwZD8fJ9_ev_t6cpbNP304P5nNMx376DNV85IJWvGSF6iitOaMgKCGFLxmVBuKsah0zqBUuQBTMKgMNjUywgjKBKLHSbbTDdewGio5WqH8RnbKyv3WVVyBZFwQwiP_6r_8qV3MZOcvZGMHSUvG84i_3OEr3_0YIPSytWH0TznohiALVKBYBb4TxKLI82Kr-PwWuOwG76JHErPYkSCYjRTbUVujPdT_CsVIjimSS7lPkRxTJBGLg8R7z_bqQ9WCOdzaxyYCL_aAClo1tVdO23DgSpELhkef3u44iJ-3tuBl0BacBmM96F6azt5ZyptbCrqxzsZHr2AD4dC1DEQi-WWM_Jj46CjiNHrwFwSZAgM</recordid><startdate>20070810</startdate><enddate>20070810</enddate><creator>Buonaguro, L</creator><creator>Devito, C</creator><creator>Tornesello, M.L</creator><creator>Schröder, U</creator><creator>Wahren, B</creator><creator>Hinkula, J</creator><creator>Buonaguro, F.M</creator><general>Elsevier Ltd</general><general>Elsevier</general><general>Elsevier Limited</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T2</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><scope>ABXSW</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>DG8</scope><scope>ZZAVC</scope></search><sort><creationdate>20070810</creationdate><title>DNA–VLP prime–boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity</title><author>Buonaguro, L ; Devito, C ; Tornesello, M.L ; Schröder, U ; Wahren, B ; Hinkula, J ; Buonaguro, F.M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c629t-af68593b68670b33f652e93d276f53cd3119bc45e8a49ed75ebd1df0d9d935903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Acquired immune deficiency syndrome</topic><topic>Administration, Intranasal</topic><topic>AIDS</topic><topic>AIDS Vaccines - administration & dosage</topic><topic>AIDS Vaccines - immunology</topic><topic>Allergy and Immunology</topic><topic>Animals</topic><topic>Antigens</topic><topic>Applied microbiology</topic><topic>Biological and medical sciences</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Epitope Mapping</topic><topic>Epitopes, B-Lymphocyte - immunology</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. 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Furthermore, the effect of the Eurocine lipid-based mucosal L3 adjuvant on the VLP immunogenicity has been assessed as well. The designed heterologous protocol is able to increase the env-specific humoral and cellular immune response, compared to the homologous protocol, which is to some extent increased by the administration of L3-adjuvanted VLP boosting dose. The anti-gag response is statistically increased in both homologous and heterologous protocols, particularly when the VLP boosting dose is adjuvanted. Immune sera from immunized animals exhibit >50% ex vivo neutralizing activity against heterologous A and B-clade viral isolates. An envelope B-cell epitope mapping shows an enhanced response against V3 epitopes all across the C2–V5 region in the heterologous prime–boost immunization strategy. The induction of humoral immunity at mucosal sites, which represents the main port of entry for the HIV-1 infection, is extremely relevant. 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subjects | Acquired immune deficiency syndrome Administration, Intranasal AIDS AIDS Vaccines - administration & dosage AIDS Vaccines - immunology Allergy and Immunology Animals Antigens Applied microbiology Biological and medical sciences Deoxyribonucleic acid DNA Epitope Mapping Epitopes, B-Lymphocyte - immunology Female Fundamental and applied biological sciences. Psychology HIV Antibodies - blood HIV Antibodies - immunology HIV Envelope Protein gp160 - immunology HIV-1 HIV-1 - classification HIV-1 - immunology Human immunodeficiency virus 1 Humoral immunity Immune response Immune system Immunity, Cellular - immunology Immunity, Mucosal - immunology Immunization Immunization, Secondary Immunogenicity Immunoglobulin G - blood Infections Laboratories Lymph Nodes - cytology Lymph Nodes - immunology MEDICIN MEDICINE Mice Microbiology Miscellaneous Mucosal adjuvants Mucosal response Prime–boost approach Proteins Spleen - cytology Spleen - immunology Vaccines Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) Vaccines, DNA - administration & dosage Vaccines, DNA - immunology Viral infections Virology Virus-like particles (VLP) |
title | DNA–VLP prime–boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity |
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