Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design.
PLoS One
; 13(11): e0206838, 2018.
Article
em En
| MEDLINE
| ID: mdl-30496299
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 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<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.
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Base de dados:
MEDLINE
Assunto principal:
Vacinas Virais
/
Infecções por HIV
/
Vacinas contra a AIDS
/
Vacinas de DNA
/
Imunogenicidade da Vacina
Tipo de estudo:
Clinical_trials
País como assunto:
Africa
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article