Cheeseman, HM;
Day, S;
McFarlane, L;
Fleck, S;
Miller, A;
Cole, T;
Sousa-Santos, N;
... Shattock, R; + view all
(2018)
Combined skin and muscle DNA priming provides enhanced humoral responses to an HIV-1 clade C envelope vaccine.
Human Gene Therapy
, 29
(9)
pp. 1011-1028.
10.1089/hum.2018.075.
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Abstract
Intradermal (i.d.) and intramuscular (i.m.) injections when administered with or without electroporation (EP) have the potential to tailor the immune response to DNA vaccination. This Phase I randomized controlled clinical trial in human immunodeficiency virus type 1–negative volunteers investigated whether the site and mode of DNA vaccination influences the quality of induced cellular and humoral immune responses following the DNA priming phase and subsequent protein boost with recombinant clade C CN54 gp140. A strategy of concurrent i.d. and i.m. DNA immunizations administered with or without EP was adopted. Subtle differences were observed in the shaping of vaccine-induced virus-specific CD4+ and CD8+ T cell–mediated immune responses between groups receiving: i.d.EP + i.m., i.d. + i.m.EP, and i.d.EP + i.m.EP regimens. The DNA priming phase induced 100% seroconversion in all of the groups. A single, non-adjuvanted protein boost induced a rapid and profound increase in binding antibodies in all groups, with a trend for higher responses in i.d.EP + i.m.EP. The magnitude of antigen-specific binding immunoglobulin G correlated with neutralization of closely matched clade C 93MW965 virus and Fc-dimer receptor binding (FcγRIIa and FcγRIIIa). These results offer new perspectives on the use of combined skin and muscle DNA immunization in priming humoral and cellular responses to recombinant protein.
Type: | Article |
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Title: | Combined skin and muscle DNA priming provides enhanced humoral responses to an HIV-1 clade C envelope vaccine |
Location: | United States |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1089/hum.2018.075 |
Publisher version: | https://doi.org/10.1089/hum.2018.075 |
Language: | English |
Additional information: | Copyright © Hannah Mary Cheeseman et al. 2018; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | HIV, DNA vaccine, electroporation, antibody, gp140 |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL UCL > Provost and Vice Provost Offices > VP: Health UCL > Provost and Vice Provost Offices > VP: Health > Translational Research Office |
URI: | https://discovery.ucl.ac.uk/id/eprint/10053563 |
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