Boosting with Subtype C CN54rgp140 Protein Adjuvanted with Glucopyranosyl Lipid Adjuvant after Priming with HIV-DNA and HIV-MVA Is Safe and Enhances Immune Responses: A Phase I Trial.
<h4>Background</h4>A vaccine against HIV is widely considered the most effective and sustainable way of reducing new infections. We evaluated the safety and impact of boosting with subtype C CN54rgp140 envelope protein adjuvanted in glucopyranosyl lipid adjuvant (GLA-AF) in Tanzanian vol...
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0155702&type=printable |
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| author | Agricola Joachim Agricola Joachim Asli Bauer Sarah Joseph Christof Geldmacher Patricia J Munseri Said Aboud Marco Missanga Philipp Mann Britta Wahren Guido Ferrari Victoria R Polonis Merlin L Robb Jonathan Weber Roger Tatoud Leonard Maboko Michael Hoelscher Eligius F Lyamuya Gunnel Biberfeld Eric Sandström Arne Kroidl Muhammad Bakari Charlotta Nilsson Sheena McCormack |
| author_facet | Agricola Joachim Agricola Joachim Asli Bauer Sarah Joseph Christof Geldmacher Patricia J Munseri Said Aboud Marco Missanga Philipp Mann Britta Wahren Guido Ferrari Victoria R Polonis Merlin L Robb Jonathan Weber Roger Tatoud Leonard Maboko Michael Hoelscher Eligius F Lyamuya Gunnel Biberfeld Eric Sandström Arne Kroidl Muhammad Bakari Charlotta Nilsson Sheena McCormack |
| author_sort | Agricola Joachim |
| collection | DOAJ |
| description | <h4>Background</h4>A vaccine against HIV is widely considered the most effective and sustainable way of reducing new infections. We evaluated the safety and impact of boosting with subtype C CN54rgp140 envelope protein adjuvanted in glucopyranosyl lipid adjuvant (GLA-AF) in Tanzanian volunteers previously given three immunizations with HIV-DNA followed by two immunizations with recombinant modified vaccinia virus Ankara (HIV-MVA).<h4>Methods</h4>Forty volunteers (35 vaccinees and five placebo recipients) were given two CN54rgp140/GLA-AF immunizations 30-71 weeks after the last HIV-MVA vaccination. These immunizations were delivered intramuscularly four weeks apart.<h4>Results</h4>The vaccine was safe and well tolerated except for one episode of asymptomatic hypoglycaemia that was classified as severe adverse event. Two weeks after the second HIV-MVA vaccination 34 (97%) of the 35 previously vaccinated developed Env-specific binding antibodies, and 79% and 84% displayed IFN-γ ELISpot responses to Gag and Env, respectively. Binding antibodies to subtype C Env (included in HIV-DNA and protein boost), subtype B Env (included only in HIV-DNA) and CRF01_AE Env (included only in HIV-MVA) were significantly boosted by the CN54rgp140/GLA-AF immunizations. Functional antibodies detected using an infectious molecular clone virus/peripheral blood mononuclear cell neutralization assay, a pseudovirus/TZM-bl neutralization assay or by assays for antibody-dependent cellular cytotoxicity (ADCC) were not significantly boosted. In contrast, T-cell proliferative responses to subtype B MN antigen and IFN-γ ELISpot responses to Env peptides were significantly enhanced. Four volunteers not primed with HIV-DNA and HIV-MVA before the CN54rgp140/GLA-AF immunizations mounted an antibody response, while cell-mediated responses were rare. After the two Env subtype C protein immunizations, a trend towards higher median subtype C Env binding antibody titers was found in vaccinees who had received HIV-DNA and HIV-MVA prior to the two Env protein immunizations as compared to unprimed vaccinees (p = 0.07).<h4>Conclusion</h4>We report excellent tolerability, enhanced binding antibody responses and Env-specific cell-mediated immune responses but no ADCC antibody increase after two immunizations with a subtype C rgp140 protein adjuvanted in GLA-AF in healthy volunteers previously immunized with HIV-DNA and HIV-MVA.<h4>Trial registration</h4>International Clinical Trials Registry PACTR2010050002122368. |
| format | Article |
| id | doaj-art-51c62ba07ec84c96b62989aa2999a67b |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-51c62ba07ec84c96b62989aa2999a67b2025-08-20T03:24:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01115e015570210.1371/journal.pone.0155702Boosting with Subtype C CN54rgp140 Protein Adjuvanted with Glucopyranosyl Lipid Adjuvant after Priming with HIV-DNA and HIV-MVA Is Safe and Enhances Immune Responses: A Phase I Trial.Agricola JoachimAgricola JoachimAsli BauerSarah JosephChristof GeldmacherPatricia J MunseriSaid AboudMarco MissangaPhilipp MannBritta WahrenGuido FerrariVictoria R PolonisMerlin L RobbJonathan WeberRoger TatoudLeonard MabokoMichael HoelscherEligius F LyamuyaGunnel BiberfeldEric SandströmArne KroidlMuhammad BakariCharlotta NilssonSheena McCormack<h4>Background</h4>A vaccine against HIV is widely considered the most effective and sustainable way of reducing new infections. We evaluated the safety and impact of boosting with subtype C CN54rgp140 envelope protein adjuvanted in glucopyranosyl lipid adjuvant (GLA-AF) in Tanzanian volunteers previously given three immunizations with HIV-DNA followed by two immunizations with recombinant modified vaccinia virus Ankara (HIV-MVA).<h4>Methods</h4>Forty volunteers (35 vaccinees and five placebo recipients) were given two CN54rgp140/GLA-AF immunizations 30-71 weeks after the last HIV-MVA vaccination. These immunizations were delivered intramuscularly four weeks apart.<h4>Results</h4>The vaccine was safe and well tolerated except for one episode of asymptomatic hypoglycaemia that was classified as severe adverse event. Two weeks after the second HIV-MVA vaccination 34 (97%) of the 35 previously vaccinated developed Env-specific binding antibodies, and 79% and 84% displayed IFN-γ ELISpot responses to Gag and Env, respectively. Binding antibodies to subtype C Env (included in HIV-DNA and protein boost), subtype B Env (included only in HIV-DNA) and CRF01_AE Env (included only in HIV-MVA) were significantly boosted by the CN54rgp140/GLA-AF immunizations. Functional antibodies detected using an infectious molecular clone virus/peripheral blood mononuclear cell neutralization assay, a pseudovirus/TZM-bl neutralization assay or by assays for antibody-dependent cellular cytotoxicity (ADCC) were not significantly boosted. In contrast, T-cell proliferative responses to subtype B MN antigen and IFN-γ ELISpot responses to Env peptides were significantly enhanced. Four volunteers not primed with HIV-DNA and HIV-MVA before the CN54rgp140/GLA-AF immunizations mounted an antibody response, while cell-mediated responses were rare. After the two Env subtype C protein immunizations, a trend towards higher median subtype C Env binding antibody titers was found in vaccinees who had received HIV-DNA and HIV-MVA prior to the two Env protein immunizations as compared to unprimed vaccinees (p = 0.07).<h4>Conclusion</h4>We report excellent tolerability, enhanced binding antibody responses and Env-specific cell-mediated immune responses but no ADCC antibody increase after two immunizations with a subtype C rgp140 protein adjuvanted in GLA-AF in healthy volunteers previously immunized with HIV-DNA and HIV-MVA.<h4>Trial registration</h4>International Clinical Trials Registry PACTR2010050002122368.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0155702&type=printable |
| spellingShingle | Agricola Joachim Agricola Joachim Asli Bauer Sarah Joseph Christof Geldmacher Patricia J Munseri Said Aboud Marco Missanga Philipp Mann Britta Wahren Guido Ferrari Victoria R Polonis Merlin L Robb Jonathan Weber Roger Tatoud Leonard Maboko Michael Hoelscher Eligius F Lyamuya Gunnel Biberfeld Eric Sandström Arne Kroidl Muhammad Bakari Charlotta Nilsson Sheena McCormack Boosting with Subtype C CN54rgp140 Protein Adjuvanted with Glucopyranosyl Lipid Adjuvant after Priming with HIV-DNA and HIV-MVA Is Safe and Enhances Immune Responses: A Phase I Trial. PLoS ONE |
| title | Boosting with Subtype C CN54rgp140 Protein Adjuvanted with Glucopyranosyl Lipid Adjuvant after Priming with HIV-DNA and HIV-MVA Is Safe and Enhances Immune Responses: A Phase I Trial. |
| title_full | Boosting with Subtype C CN54rgp140 Protein Adjuvanted with Glucopyranosyl Lipid Adjuvant after Priming with HIV-DNA and HIV-MVA Is Safe and Enhances Immune Responses: A Phase I Trial. |
| title_fullStr | Boosting with Subtype C CN54rgp140 Protein Adjuvanted with Glucopyranosyl Lipid Adjuvant after Priming with HIV-DNA and HIV-MVA Is Safe and Enhances Immune Responses: A Phase I Trial. |
| title_full_unstemmed | Boosting with Subtype C CN54rgp140 Protein Adjuvanted with Glucopyranosyl Lipid Adjuvant after Priming with HIV-DNA and HIV-MVA Is Safe and Enhances Immune Responses: A Phase I Trial. |
| title_short | Boosting with Subtype C CN54rgp140 Protein Adjuvanted with Glucopyranosyl Lipid Adjuvant after Priming with HIV-DNA and HIV-MVA Is Safe and Enhances Immune Responses: A Phase I Trial. |
| title_sort | boosting with subtype c cn54rgp140 protein adjuvanted with glucopyranosyl lipid adjuvant after priming with hiv dna and hiv mva is safe and enhances immune responses a phase i trial |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0155702&type=printable |
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