Combined Skin and Muscle DNA Priming Provides Enhanced Humoral Responses to a Human Immunodeficency Virus Type 1 Clade C Envelope Vaccine

HM Cheeseman, S Day, LR McFarlane, S Fleck, A Miller, T Cole, N Sousa-Santos, A Cope, D Cizmeci, M Tolazzi, E Hwekwete, D Hannaman, S Kratochvil, PF McKay, AW Chung, SJ Kent, A Cook, G Scarlatti, S Abraham, B CombadiereS McCormack, DJ Lewis, RJ Shattock

Research output: Contribution to journalArticle

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.EPregimens. 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. © Copyright 2018, Mary Ann Liebert, Inc., publishers2018.
Original languageEnglish
Pages (from-to)1011-1028
Number of pages18
JournalHuman Gene Therapy
Volume29
Issue number9
DOIs
Publication statusPublished - 2018

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Electroporation
Vaccines
Viruses
Muscles
Skin
DNA
Immunization
Vaccination
Intradermal Injections
Clinical Trials, Phase I
Fc Receptors
Intramuscular Injections
Humoral Immunity
Recombinant Proteins
Cellular Immunity
HIV-1
Volunteers
Proteins
Randomized Controlled Trials
Immunoglobulin G

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Combined Skin and Muscle DNA Priming Provides Enhanced Humoral Responses to a Human Immunodeficency Virus Type 1 Clade C Envelope Vaccine. / Cheeseman, HM; Day, S; McFarlane, LR; Fleck, S; Miller, A; Cole, T; Sousa-Santos, N; Cope, A; Cizmeci, D; Tolazzi, M; Hwekwete, E; Hannaman, D; Kratochvil, S; McKay, PF; Chung, AW; Kent, SJ; Cook, A; Scarlatti, G; Abraham, S; Combadiere, B; McCormack, S; Lewis, DJ; Shattock, RJ.

In: Human Gene Therapy, Vol. 29, No. 9, 2018, p. 1011-1028.

Research output: Contribution to journalArticle

Cheeseman, HM, Day, S, McFarlane, LR, Fleck, S, Miller, A, Cole, T, Sousa-Santos, N, Cope, A, Cizmeci, D, Tolazzi, M, Hwekwete, E, Hannaman, D, Kratochvil, S, McKay, PF, Chung, AW, Kent, SJ, Cook, A, Scarlatti, G, Abraham, S, Combadiere, B, McCormack, S, Lewis, DJ & Shattock, RJ 2018, 'Combined Skin and Muscle DNA Priming Provides Enhanced Humoral Responses to a Human Immunodeficency Virus Type 1 Clade C Envelope Vaccine', Human Gene Therapy, vol. 29, no. 9, pp. 1011-1028. https://doi.org/10.1089/hum.abc2018.075
Cheeseman, HM ; Day, S ; McFarlane, LR ; Fleck, S ; Miller, A ; Cole, T ; Sousa-Santos, N ; Cope, A ; Cizmeci, D ; Tolazzi, M ; Hwekwete, E ; Hannaman, D ; Kratochvil, S ; McKay, PF ; Chung, AW ; Kent, SJ ; Cook, A ; Scarlatti, G ; Abraham, S ; Combadiere, B ; McCormack, S ; Lewis, DJ ; Shattock, RJ. / Combined Skin and Muscle DNA Priming Provides Enhanced Humoral Responses to a Human Immunodeficency Virus Type 1 Clade C Envelope Vaccine. In: Human Gene Therapy. 2018 ; Vol. 29, No. 9. pp. 1011-1028.
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