Journal Article

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

Jani, Ilesh V., Munseri, Patricia J., Bauer, Asli, Joachim, Agricola, Bakari, Muhammad, Robb, Merlin L., Weber, Jonathan, Fleck, Sue, Scarlatti, Gabriella, Hoelscher, Michael, Biberfeld, Gunnel, Geldmacher, Christof, Tembe, Nelson, Joseph, Sarah, Sandström, Eric, Wahren, Britta, Viegas, Edna O., Lyamuya, Eligius, Aboud, Said, McCormack, Sheena, Nilsson, Charlotta, Maboko, Leonard, Stöhr, Wolfgang, Missanga, Marco, Kroidl, Arne, Mann, Philipp

2018

Overview

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. 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. 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. 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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acquired immune deficiency syndrome / Administration, Cutaneous / Adult / Adults / AIDS / AIDS vaccines / AIDS Vaccines - administration & dosage / AIDS Vaccines - adverse effects / AIDS Vaccines - genetics / AIDS Vaccines - immunology / Antibodies, Neutralizing - blood / Antibodies, Neutralizing - immunology / Antigens / Audio frequencies / Biology and Life Sciences / Care and treatment / Clinical trials / Deoxyribonucleic acid / DNA / DNA vaccines / Electroporation / env Gene Products, Human Immunodeficiency Virus - genetics / env Gene Products, Human Immunodeficiency Virus - immunology / Enzyme-linked immunosorbent assay / Female / Gag protein / Genetic research / Glucosides - immunology / Glycoprotein gp120 / Glycoprotein gp160 / Health aspects / Healthy Volunteers / HIV / HIV Antibodies - blood / HIV Antibodies - immunology / HIV infections / HIV Infections - prevention & control / HIV-1 - immunology / Hospitals / Human immunodeficiency virus / Humans / Immune response / Immunization / Immunization, Secondary - methods / Immunogenicity / Immunogenicity, Vaccine / Immunoglobulins / Immunology / Infections / Infectious diseases / Internal medicine / Laboratories / Lipid A / Lipid A - immunology / Lipids / Male / Medical research / Medicine / Medicine and Health Sciences / Molybdenum alloys / Mozambique / Peptides / Priming / Proteins / Public health / Randomization / Research and Analysis Methods / Risk factors / Safety / Tanzania / Vaccination / Vaccination - methods / Vaccines / Vaccines, DNA - administration & dosage / Vaccines, DNA - adverse effects / Vaccines, DNA - genetics / Vaccines, DNA - immunology / Vaccinia / Vaccinia virus - immunology / Viral envelope proteins / Viral Vaccines - administration & dosage / Viral Vaccines - adverse effects / Viral Vaccines - genetics / Viral Vaccines - immunology / Viruses / Young Adult / γ-Interferon