IMPORTANCE Developing effective vaccines against Ebola virus is a global priority. OBJECTIVE To evaluate an adenovirus type 26 vector vaccine encoding Ebola glycoprotein (Ad26.ZEBOV) and a modified vaccinia Ankara vector vaccine, encoding glycoproteins from Ebola virus, Sudan virus, Marburg virus, and Tai Forest virus nucleoprotein (MVA-BN-Filo). DESIGN, SETTING, AND PARTICIPANTS Single-center, randomized, placebo-controlled, observer-blind, phase 1 trial performed in Oxford, United Kingdom, enrolling healthy 18-to 50-year-olds from December 2014; 8-month follow-up was completed October 2015. INTERVENTIONS Participants were randomized into 4 groups, within which they were simultaneously randomized 5:1 to receive study vaccines or placebo. Those receiving active vaccines were primed with Ad26.ZEBOV (5 × 10 10 viral particles) or MVA-BN-Filo (1 × 10 8 median tissue culture infective dose) and boosted with the alternative vaccine 28 or 56 days later. A fifth, open-label group received Ad26.ZEBOV boosted by MVA-BN-Filo 14 days later. MAIN OUTCOMES AND MEASURES The primary outcomes were safety and tolerability. All adverse events were recorded until 21 days after each immunization; serious adverse events were recorded throughout the trial. Secondary outcomes were humoral and cellular immune responses to immunization, as assessed by enzyme-linked immunosorbent assay and enzyme-linked immunospot performed at baseline and from 7 days after each immunization until 8 months after priming immunizations. RESULTS Among 87 study participants (median age, 38.5 years; 66.7% female), 72 were randomized into 4 groups of 18, and 15 were included in the open-label group. Four participants did not receive a booster dose; 67 of 75 study vaccine recipients were followed up at 8 months. No vaccine-related serious adverse events occurred. No participant became febrile after MVA-BN-Filo, compared with 3 of 60 participants (5%; 95% CI, 1%-14%) receiving Ad26.ZEBOV in the randomized groups. In the open-label group, 4 of 15 Ad26.ZEBOV recipients (27%; 95% CI, 8%-55%) experienced fever. In the randomized groups, 28 of 29 Ad26.ZEBOV recipients (97%; 95% CI, 82%-99.9%) and 7 of 30 MVA-BN-Filo recipients (23%; 95% CI, 10%-42%) had detectable Ebola glycoprotein-specific IgG 28 days after primary immunization. All vaccine recipients had specific IgG detectable 21 days postboost and at 8-month follow-up. Within randomized groups, at 7 days postboost, at least 86% of vaccine recipients showed Ebola-specific T-cell responses. CONCLUSIONS AND RELEVANCE In this phase 1 study of healthy volunteers, immunization with Ad26.ZEBOV or MVA-BN-Filo did not result in any vaccine-related serious adverse events. An immune response was observed after primary immunization with Ad26.ZEBOV; boosting by MVA-BN-Filo resulted in sustained elevation of specific immunity. These vaccines are being further assessed in phase 2 and 3 studies.

Background: Better communication is often suggested as fundamental to increasing the use of research evidence in policy, but little is known about how researchers and policy makers work together or about barriers to exchange. This study explored the views and practice of policy makers and researchers regarding the use of evidence in policy, including: (i) current use of research to inform policy; (ii) dissemination of and access to research findings for policy; (iii) communication and exchange between researchers and policy makers; and (iv) incentives for increasing the use of research in policy.

The adoption of the strategy of negotiated safety among men in HIV-seronegative regular relationships may help such men sustain the safety of their sexual practice.

A case control analysis within an ongoing cohort study was used to examine differences between seroconverters and men who remained HIV-negative. The cases were interviewed within one to 13 months prior to their seroconversion. Their responses to a structured questionnaire were compared with those of HIV-negative controls drawn from the same time period and from the same longitudinal study, Sydney Men and Sexual Health. Data collected from both cases and controls included: demographic and contextual variables, knowledge of HIV transmission, sexual practices, drug and alcohol use and attitudinal factors. The aim was to compare the sexual behaviours, and the social and cultural contexts of such behaviours, of men prior to their HIV seroconversion with men who did not seroconvert. Twenty-three men had seroconverted within the cohort. Cases were identified by a positive HIV antibody test or self-report of positive HIV status following a previous negative HIV test. Three-hundred-and-sixty-nine controls were selected on the basis of being HIV negative at interview in 1994, and having at least one subsequent medically-confirmed negative HIV antibody test. Univariate predictors of seroconversion were: being in a regular relationship with a known HIV-positive partner, drug use, and engaging in a range of anal and esoteric sexual practices. Practices commonly used to enhance sexual pleasure, such as group sex, watching and being watched having sex, the use of sex toys and dressing up/fantasy, were engaged in more frequently by seroconverters. Engaging in these esoteric sexual practices was highly correlated with drug use, involvement in the gay community and engagement in a wide range of anal practices. In the multivariate analysis independent predictors of seroconversion were: younger age; being in a regular relationship with a known HIV-positive partner; believing withdrawal to be safe with regard to HIV transmission; and range of esoteric practices. These results indicate the importance of the social and cultural contexts of particular sexual practices and consequent HIV transmission. Sexually adventurous men may be at increased risk for HIV because they seek sex within particular sexual sub-cultures.

SummaryThe safe establishment of a protocol for a human challenge model for Salmonella Paratyphi A can be used to expedite the evaluation of novel vaccine candidates and provides insight into the clinical and immune response to paratyphoid infection.