ABSTRACT
BACKGROUND: An approach to a preventive HIV vaccine is induction of effective broadly neutralizing antibodies (bnAbs) and effector binding antibodies (bAbs). Preclinical studies suggest that trimeric envelope (Env) proteins may elicit nAbs, which led to the development of the recombinant gp145 subtype C Env protein (gp145 C.6980) immunogen. HVTN 122 was a Phase 1 trial that evaluated the safety, tolerability, and immunogenicity of gp145 C.6980 in adults. METHODS: Healthy, HIV-1 seronegative adults received three intramuscular injections of gp145 C.6980 with aluminum hydroxide (alum) at months 0, 2, and 6 at either 300 mcg (high dose, n = 25) or 100 mcg (low dose, n = 15), or placebo/saline (placebo, n = 5). Participants were followed for 12 months. RESULTS: Forty-five participants were enrolled. High and low doses of the study protein were well-tolerated, with mild or moderate reactogenicity commonly reported. Only one adverse event (mild injection site pruritis) in one participant (low dose) was considered product-related; there were no dose-limiting toxicities. High and low dose recipients demonstrated robust bAb responses to vaccine-matched consensus gp140 Env and subtype-matched gp120 Env proteins two weeks post-last vaccination (response rates >90 %), while no responses were detected to a heterologous subtype-matched V1V2 antigen. No significant differences were seen between high and low dose groups. Participants in both experimental arms demonstrated nAb response rates of 76.5 % to a tier 1 virus (MW9635.26), but no responses to tier 2 isolates. Env-specific CD4 + T-cell responses were elicited in 36.4 % of vaccine recipients, without significant differences between groups; no participants demonstrated CD8 + T-cell responses. CONCLUSIONS: Three doses of novel subtype C gp145 Env protein with alum were safe and well-tolerated. Participants demonstrated bAb, Env-specific CD4 + T-cell, and tier 1 nAb responses, but the regimen failed to induce tier 2 or heterologous nAb responses. CLINICAL TRIALS REGISTRATION: NCT03382418.
ABSTRACT
OBJECTIVES: Secondhand smoke (SHS) and other air pollutants adversely affect the health of pregnant women and infants. A feasibility study aimed at reducing air pollution in homes of pregnant women or infants living with a smoker was completed. METHODS: In collaboration with the Baltimore City Health Department, women ≥ 18 years of age and either pregnant nonsmokers, or post-partum (any smoking status) with an infant age 0-12 months were recruited. Homes had at least one smoker. Intervention included two air purifiers and secondhand smoke education. Outcomes included feasibility, change in fine particulate matter (PM2.5), air nicotine, and salivary cotinine pre- and post-intervention. RESULTS: Fifty women were enrolled (mean age 27 years, 92% African American, 71% single, 94% Medicaid eligible, 34% reported smoking) and 86% completed the study. Of the 50 women, 32 had infants and 18 were pregnant at time of enrollment. Post- intervention, 70% of participants reported smokers were less likely to smoke indoors, and 77% had at least one air purifier turned on at the final visit. Participant satisfaction was high (91%) and 98% would recommend air purifiers. Indoor PM2.5 was significantly decreased (P < 0.001). Salivary cotinine was significantly decreased for non-smoking women (P < 0.01) but not infants, and no significant change in air nicotine occurred (P = 0.6). CONCLUSIONS: Air purifiers with SHS education is a feasible intervention in homes of women and infants. These data demonstrate reduction in indoor PM2.5 and salivary cotinine in non-smoking adults. Air purifiers are not an alternative for smoking cessation and a home/ car smoking ban. Smoking cessation should be strongly encouraged for all pregnant women, and nonsmoking mothers with infants should be counseled to completely avoid SHS exposure. This study provides support for a future intervention evaluating clinical endpoints.
