| Title: |
Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design |
| Authors: |
Viegas, EO; Kroidl, A; Munseri, PJ; Missanga, M; Nilsson, C; Tembe, N; Bauer, A; Joachim, A; Joseph, S; Mann, P; Geldmacher, C; Fleck, S; Stöhr, W; Scarlatti, G; Aboud, S; Bakari, M; Maboko, L; Hoelscher, M; Wahren, B; Robb, ML; Weber, J; McCormack, S; Biberfeld, G; Jani, IV; Sandström, E; Lyamuya, E |
| Source: |
PLoS One , 13 (11) , Article e0206838. (2018) |
| Publication Year: |
2018 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
Vaccines; Immune response; Antibodies; Antibody response; Adverse events; HIV infections; Enzyme-linked immunoassays; Vaccination and immunization |
| Description: |
BACKGROUND: We evaluated the safety and immunogenicity of (i) an intradermal HIV-DNA regimen given with/without intradermal electroporation (EP) as prime and (ii) the impact of boosting with modified vaccinia virus Ankara (HIV-MVA) administered with or without subtype C CN54rgp140 envelope protein adjuvanted with Glucopyranosyl Lipid A (GLA-AF) in volunteers from Tanzania and Mozambique. METHODS: Healthy HIV-uninfected adults (N = 191) were randomized twice; first to one of three HIV-DNA intradermal priming regimens by needle-free ZetaJet device at weeks 0, 4 and 12 (Group I: 2x0.1mL [3mg/mL], Group II: 2x0.1mL [3mg/mL] plus EP, Group III: 1x0.1mL [6mg/mL] plus EP). Second the same volunteers received 108 pfu HIV-MVA twice, alone or combined with CN54rgp140/GLA-AF, intramuscularly by syringe, 16 weeks apart. Additionally, 20 volunteers received saline placebo. RESULTS: Vaccinations and electroporation did not raise safety concerns. After the last vaccination, the overall IFN-γ ELISpot response rate to either Gag or Env was 97%. Intradermal electroporation significantly increased ELISpot response rates to HIV-DNA-specific Gag (66% group I vs. 86% group II, p = 0.026), but not to the HIV-MVA vaccine-specific Gag or Env peptide pools nor the magnitude of responses. Co-administration of rgp140/GLA-AF with HIV-MVA did not impact the frequency of binding antibody responses against subtype B gp160, C gp140 or E gp120 antigens (95%, 99%, 79%, respectively), but significantly enhanced the magnitude against subtype B gp160 (2700 versus 300, p |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10063215/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10063215/1/Stohr_Optimizing%20the%20immunogenicity%20of%20HIV%20prime-boost%20DNA-MVA-rgp140%20GLA%20vaccines%20in%20a%20phase%20II%20randomized%20factorial%20trial%20design_VoR.pdf; https://discovery.ucl.ac.uk/id/eprint/10063215/ |
| Rights: |
open |
| Accession Number: |
edsbas.A9DDFC45 |
| Database: |
BASE |