A phase I randomized clinical trial of candidate human immunodeficiency virus type 1 vaccine MVA.HIVA administered to Gambian infants.
<h4>Background</h4>A vaccine to decrease transmission of human immunodeficiency virus type 1 (HIV-1) during breast-feeding would complement efforts to eliminate infant HIV-1 infection by antiretroviral therapy. Relative to adults, infants have distinct immune development, potentially hig...
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Public Library of Science (PLoS)
2013-01-01
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| author | Muhammed O Afolabi Jorjoh Ndure Abdoulie Drammeh Fatoumatta Darboe Shams-Rony Mehedi Sarah L Rowland-Jones Nicola Borthwick Antony Black Gwen Ambler Grace C John-Stewart Marie Reilly Tomáš Hanke Katie L Flanagan |
| author_facet | Muhammed O Afolabi Jorjoh Ndure Abdoulie Drammeh Fatoumatta Darboe Shams-Rony Mehedi Sarah L Rowland-Jones Nicola Borthwick Antony Black Gwen Ambler Grace C John-Stewart Marie Reilly Tomáš Hanke Katie L Flanagan |
| author_sort | Muhammed O Afolabi |
| collection | DOAJ |
| description | <h4>Background</h4>A vaccine to decrease transmission of human immunodeficiency virus type 1 (HIV-1) during breast-feeding would complement efforts to eliminate infant HIV-1 infection by antiretroviral therapy. Relative to adults, infants have distinct immune development, potentially high-risk of transmission when exposed to HIV-1 and rapid progression to AIDS when infected. To date, there have been only three published HIV-1 vaccine trials in infants.<h4>Trial design</h4>We conducted a randomized phase I clinical trial PedVacc 001 assessing the feasibility, safety and immunogenicity of a single dose of candidate vaccine MVA.HIVA administered intramuscularly to 20-week-old infants born to HIV-1-negative mothers in The Gambia.<h4>Methods</h4>Infants were followed to 9 months of age with assessment of safety, immunogenicity and interference with Expanded Program on Immunization (EPI) vaccines. The trial is the first stage of developing more complex prime-boost vaccination strategies against breast milk transmission of HIV-1.<h4>Results</h4>From March to October 2010, 48 infants (24 vaccine and 24 no-treatment) were enrolled with 100% retention. The MVA.HIVA vaccine was safe with no difference in adverse events between vaccinees and untreated infants. Two vaccine recipients (9%) and no controls had positive ex vivo interferon-γ ELISPOT assay responses. Antibody levels elicited to the EPI vaccines, which included diphtheria, tetanus, whole-cell pertussis, hepatitis B virus, Haemophilus influenzae type b and oral poliovirus, reached protective levels for the vast majority and were similar between the two arms.<h4>Conclusions</h4>A single low-dose of MVA.HIVA administered to 20-week-old infants in The Gambia was found to be safe and without interference with the induction of protective antibody levels by EPI vaccines, but did not alone induce sufficient HIV-1-specific responses. These data support the use of MVA carrying other transgenes as a boosting vector within more complex prime-boost vaccine strategies against transmission of HIV-1 and/or other infections in this age group.<h4>Trial registration</h4>ClinicalTrials.gov NCT00982579. The Pan African Clinical Trials Registry PACTR2008120000904116. |
| format | Article |
| id | doaj-art-a3c793ec74e54deb89c8c5aa9ab53bca |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-a3c793ec74e54deb89c8c5aa9ab53bca2025-08-20T03:10:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7828910.1371/journal.pone.0078289A phase I randomized clinical trial of candidate human immunodeficiency virus type 1 vaccine MVA.HIVA administered to Gambian infants.Muhammed O AfolabiJorjoh NdureAbdoulie DrammehFatoumatta DarboeShams-Rony MehediSarah L Rowland-JonesNicola BorthwickAntony BlackGwen AmblerGrace C John-StewartMarie ReillyTomáš HankeKatie L Flanagan<h4>Background</h4>A vaccine to decrease transmission of human immunodeficiency virus type 1 (HIV-1) during breast-feeding would complement efforts to eliminate infant HIV-1 infection by antiretroviral therapy. Relative to adults, infants have distinct immune development, potentially high-risk of transmission when exposed to HIV-1 and rapid progression to AIDS when infected. To date, there have been only three published HIV-1 vaccine trials in infants.<h4>Trial design</h4>We conducted a randomized phase I clinical trial PedVacc 001 assessing the feasibility, safety and immunogenicity of a single dose of candidate vaccine MVA.HIVA administered intramuscularly to 20-week-old infants born to HIV-1-negative mothers in The Gambia.<h4>Methods</h4>Infants were followed to 9 months of age with assessment of safety, immunogenicity and interference with Expanded Program on Immunization (EPI) vaccines. The trial is the first stage of developing more complex prime-boost vaccination strategies against breast milk transmission of HIV-1.<h4>Results</h4>From March to October 2010, 48 infants (24 vaccine and 24 no-treatment) were enrolled with 100% retention. The MVA.HIVA vaccine was safe with no difference in adverse events between vaccinees and untreated infants. Two vaccine recipients (9%) and no controls had positive ex vivo interferon-γ ELISPOT assay responses. Antibody levels elicited to the EPI vaccines, which included diphtheria, tetanus, whole-cell pertussis, hepatitis B virus, Haemophilus influenzae type b and oral poliovirus, reached protective levels for the vast majority and were similar between the two arms.<h4>Conclusions</h4>A single low-dose of MVA.HIVA administered to 20-week-old infants in The Gambia was found to be safe and without interference with the induction of protective antibody levels by EPI vaccines, but did not alone induce sufficient HIV-1-specific responses. These data support the use of MVA carrying other transgenes as a boosting vector within more complex prime-boost vaccine strategies against transmission of HIV-1 and/or other infections in this age group.<h4>Trial registration</h4>ClinicalTrials.gov NCT00982579. The Pan African Clinical Trials Registry PACTR2008120000904116.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0078289&type=printable |
| spellingShingle | Muhammed O Afolabi Jorjoh Ndure Abdoulie Drammeh Fatoumatta Darboe Shams-Rony Mehedi Sarah L Rowland-Jones Nicola Borthwick Antony Black Gwen Ambler Grace C John-Stewart Marie Reilly Tomáš Hanke Katie L Flanagan A phase I randomized clinical trial of candidate human immunodeficiency virus type 1 vaccine MVA.HIVA administered to Gambian infants. PLoS ONE |
| title | A phase I randomized clinical trial of candidate human immunodeficiency virus type 1 vaccine MVA.HIVA administered to Gambian infants. |
| title_full | A phase I randomized clinical trial of candidate human immunodeficiency virus type 1 vaccine MVA.HIVA administered to Gambian infants. |
| title_fullStr | A phase I randomized clinical trial of candidate human immunodeficiency virus type 1 vaccine MVA.HIVA administered to Gambian infants. |
| title_full_unstemmed | A phase I randomized clinical trial of candidate human immunodeficiency virus type 1 vaccine MVA.HIVA administered to Gambian infants. |
| title_short | A phase I randomized clinical trial of candidate human immunodeficiency virus type 1 vaccine MVA.HIVA administered to Gambian infants. |
| title_sort | phase i randomized clinical trial of candidate human immunodeficiency virus type 1 vaccine mva hiva administered to gambian infants |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0078289&type=printable |
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