1. First-in-Human Randomized, Controlled Trial of Mosaic HIV-1 Immunogens Delivered via a Modified Vaccinia Ankara Vector.
- Author
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Baden LR, Walsh SR, Seaman MS, Cohen YZ, Johnson JA, Licona JH, Filter RD, Kleinjan JA, Gothing JA, Jennings J, Peter L, Nkolola J, Abbink P, Borducchi EN, Kirilova M, Stephenson KE, Pegu P, Eller MA, Trinh HV, Rao M, Ake JA, Sarnecki M, Nijs S, Callewaert K, Schuitemaker H, Hendriks J, Pau MG, Tomaka F, Korber BT, Alter G, Dolin R, Earl PL, Moss B, Michael NL, Robb ML, and Barouch DH
- Subjects
- AIDS Vaccines adverse effects, AIDS Vaccines genetics, Adult, Double-Blind Method, Drug Carriers, Drug-Related Side Effects and Adverse Reactions epidemiology, Drug-Related Side Effects and Adverse Reactions pathology, Female, Genetic Vectors, Humans, Immunity, Cellular, Immunity, Humoral, Longitudinal Studies, Male, Middle Aged, Placebos administration & dosage, Treatment Outcome, Vaccines, Subunit administration & dosage, Vaccines, Subunit adverse effects, Vaccines, Subunit genetics, Vaccines, Subunit immunology, Vaccines, Synthetic administration & dosage, Vaccines, Synthetic adverse effects, Vaccines, Synthetic genetics, Vaccines, Synthetic immunology, Vaccinia virus genetics, Young Adult, AIDS Vaccines administration & dosage, AIDS Vaccines immunology, HIV Infections prevention & control, HIV-1 immunology
- Abstract
Background: Mosaic immunogens are bioinformatically engineered human immunodeficiency virus type 1 (HIV-1) sequences designed to elicit clade-independent coverage against globally circulating HIV-1 strains., Methods: This phase 1, double-blinded, randomized, placebo-controlled trial enrolled healthy HIV-uninfected adults who received 2 doses of a modified vaccinia Ankara (MVA)-vectored HIV-1 bivalent mosaic immunogen vaccine or placebo on days 0 and 84. Two groups were enrolled: those who were HIV-1 vaccine naive (n = 15) and those who had received an HIV-1 vaccine (Ad26.ENVA.01) 4-6 years earlier (n = 10). We performed prespecified blinded cellular and humoral immunogenicity analyses at days 0, 14, 28, 84, 98, 112, 168, 270, and 365., Results: All 50 planned vaccinations were administered. Vaccination was safe and generally well tolerated. No vaccine-related serious adverse events occurred. Both cellular and humoral cross-clade immune responses were elicited after 1 or 2 vaccinations in all participants in the HIV-1 vaccine-naive group. Env-specific responses were induced after a single immunization in nearly all subjects who had previously received the prototype Ad26.ENVA.01 vaccine., Conclusions: No safety concerns were identified, and multiclade HIV-1-specific immune responses were elicited., Clinical Trials Registration: NCT02218125.
- Published
- 2018
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