Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design

Viegas, Edna O.; Kroidl, Arne; Munseri, Patricia J.; Missanga, Marco; Nilsson, Charlotte; Tembe, Nelson; Bauer, Asli; Joachim, Agricola; Joseph, Sarah; Mann, Philipp; Geldmacher, Christof; Fleck, Sue; Stohr, Wolfgang; Scarlatti, Gabriella; Aboud, Said; Bakari, Muhammad; Maboko, Leonard; Hoelscher, Michael; Wahren, Britta; Robb, Merlin L.; Weber, Jonathan; McCormack, Sheena; Biberfeld, Gunnel; Jani, Ilesh; Sandstrom, Eric und Lyamuya, Eligius (2018): Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design.
In: PLOS One 13(11), e0206838

Abstract

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 10(8) 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-gamma 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<0.001) and subtype C gp140 (24300 versus 2700, p<0.001) Env protein. At relatively low titers, neutralizing antibody responses using the TZM-bl assay were more frequent in vaccinees given adjuvanted protein boost. Conclusion Intradermal electroporation increased DNA-induced Gag response rates but did not show an impact on Env-specific responses nor on the magnitude of responses. Co-administration of HIV-MVA with rgp140/GLA-AF significantly enhanced antibody responses.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1932-6203
• Sprache: Englisch