Serologic responses and systemic reactions in adults after vaccination with monovalent A/USSR/77 and trivalent A/USSR/77, A/Texas/77, B/Hong Kong/72 influenza vaccines

Four hundred twenty-six volunteers aged 16 to 83 years were given experimental doses of inactivated monovalent [A/USSR/77 (H1N1)] and trivalent [A/USSR/77 (H1N1), A/Texas/77 (H3N2), B/Hong Kong/72] influenza vaccines as part of a double-blinded, placebo-controlled, national collaborative study. Local reactions at inoculation sites occurred in less than 6.6% of volunteers. Systemic reactions, generally consisting of low-grade fever, myalgia, or headache, lasting less than 24 hr, did not occur more frequently in vaccinees than in placebo recipients. Vaccines containing lower doses of the A/Texas/77 (H3N2) hemagglutinin (8-10 micrograms) and B/Hong Kong/72 hemagglutinin (6-9 micrograms) produced hemagglutinin-inhibiting (HAI) antibody responses equivalent to those produced by higher doses (15-28 and 19-28 micrograms, respectively) in all age groups. Single injections of vaccines containing lower doses of A/USSR/77 (H1N1) hemagglutinin (4-7 micrograms) induced titers of HAI antibody of greater than 1:40 in 93% of volunteers greater than or equal to 26 years of age but in only 58% of volunteers less than 26 years of age. In this latter group, two injections containing higher doses (10-19 micrograms) induced better antibody responses. Vaccines containing approximately 6-15 micrograms of hemagglutinin of each antigen can be expected to be well tolerated and to induce good HAI antibody responses in a one- or two-dose regimen, depending on the age group

Characterization of humoral and cellular immune responses elicited by a recombinant adenovirus serotype 26 HIV-1 Env vaccine in healthy adults (IPCAVD 001)

Adenovirus serotype 26 (Ad26) has been developed as a novel candidate vaccine vector for human immunodeficiency virus type 1 (HIV-1) and other pathogens. The primary safety and immunogenicity data from the Integrated Preclinical/Clinical AIDS Vaccine Development Program (IPCAVD) 001 trial, the first-in-human evaluation of a prototype Ad26 vector-based vaccine expressing clade A HIV-1 Env (Ad26.ENVA.01), are reported concurrently with this article. Here, we characterize in greater detail the humoral and cellular immune responses elicited by Ad26.ENVA.01 in humans. Samples from the IPCAVD 001 trial were used for humoral and cellular immunogenicity assays. We observed a dose-dependent expansion of the magnitude, breadth, and epitopic diversity of Env-specific binding antibody responses elicited by this vaccine. Antibody-dependent cell-mediated phagocytosis, virus inhibition, and degranulation functional activity were also observed. Env-specific cellular immune responses induced by the vaccine included multiple CD8(+) and CD4(+) T-lymphocyte memory subpopulations and cytokine secretion phenotypes, although cellular immune breadth was limited. Baseline vector-specific T-lymphocyte responses were common but did not impair Env-specific immune responses in this study. Ad26.ENVA.01 elicited a broad diversity of humoral and cellular immune responses in humans. These data support the further clinical development of Ad26 as a candidate vaccine vector. NCT0061860

First-in-human evaluation of the safety and immunogenicity of a recombinant adenovirus serotype 26 HIV-1 Env vaccine (IPCAVD 001)

We report the first-in-human safety and immunogenicity assessment of a prototype Ad26 vector-based human immunodeficiency virus (HIV) vaccine in humans. Sixty Ad26-seronegative, healthy, HIV-uninfected subjects were enrolled in a randomized, double-blinded, placebo-controlled, dose-escalation phase 1 study. Five groups of 12 subjects received 10(9)-10(11) vp of the Ad26-EnvA vaccine (N = 10/group) or placebo (N = 2/group) at weeks 0 and 24 or weeks 0, 4, and 24. Safety and immunogenicity were assessed. Self-limited reactogenicity was observed after the initial immunization at the highest (10(11) vp) dose. No product-related SAEs were observed. All subjects who received the Ad26-EnvA vaccine developed Ad26 NAb titers, EnvA-specific enzyme-linked immunosorbent assays (ELISA) titers, and EnvA-specific enzyme-linked immunospot assays (ELISPOT) responses. These responses persisted at week 52. At week 28 in the 10(9), 10(10), 10(11) vp 3-dose and the 10(10) and 5 × 10(10) vp 2-dose groups, geometric mean EnvA ELISA titers were 6113, 12 470, 8545, 3470, and 9655 and mean EnvA ELISPOT responses were 397, 178, 736, 196, and 1311 SFC/10(6) peripheral blood mononuclear cells, respectively. This Ad26 vectored vaccine was generally safe and immunogenic at all doses tested. Reactogenicity was minimal with doses of 5 × 10(10) vp or less. Ad26 is a promising new vaccine vector for HIV-1. NCT0061860