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Background: Risks to mother and fetus following Ebola virus infection are very high. Evaluation of safety and immunogenicity of non-replicating Ebola vaccine candidates is a priority for use in pregnant women. This is the protocol for a randomized, open-label, single-center phase 3 clinical trial of the safety, reactogenicity, and immunogenicity of the 2-dose Ebola vaccine regimen in healthy adult pregnant women. This 2-dose regimen has been shown to be safe, judged effective, and approved in non-pregnant populations.Methods: A total of 2000 adult (≥ 18 years of age) pregnant women will be enrolled from antenatal care facilities in Western Rwanda and randomized (1:1) to receive the 2-dose Ebola vaccine regimen (Ad26.ZEBOV, MVA-BN-Filo (group A)) or control (unvaccinated pregnant women (group B)). The primary objectives are to (1) assess adverse maternal/fetal outcomes in randomized pregnant women up to 1.5 months after delivery and (2) assess adverse neonatal/infant outcomes in neonates/infants born to randomized women up to 3.5 months after birth. The frequency and relatedness of all serious adverse events in women and newborns from randomization or birth, respectively, until study end will be reported. The reactogenicity and unsolicited adverse events of the 2-dose Ebola vaccine regimen in all vaccinated pregnant women (group A) will be reported. We will also assess the immunogenicity of the 2-dose Ebola vaccine regimen in 150 pregnant women who are anticipated to receive both vaccine doses within the course of their pregnancy (a subset of the 1000 pregnant vaccinated women from group A) compared to 150 non-pregnant women vaccinated after delivery (a subset of group B). The persistence of maternal antibodies in 75 infants born to women from the group A subset will be assessed. Exploratory analyses include assessment of acceptability of the 2-dose Ebola vaccine regimen among group A and assessment of maternal antibodies in breast milk in 50 women from group A and 10 controls (women from group B prior to vaccination).Discussion: This study is intended to support a label variation to relax restrictions on use in pregnant women, a vulnerable population with high medical need.Trial Registration: Clinicaltrials.gov NCT04556526 . September 21, 2020. [ABSTRACT FROM AUTHOR]

Introduction: Couples' voluntary HIV counselling and testing (CVCT) is a high‐impact HIV prevention intervention in Rwanda and Zambia. Our objective was to model the cost‐per‐HIV infection averted by CVCT in six African countries guided by an HIV prevention cascade framework. The HIV prevention cascade as yet to be applied to evaluating CVCT effectiveness or cost‐effectiveness. Methods: We defined a priority population for CVCT in Africa as heterosexual adults in stable couples. Based on our previous experience nationalizing CVCT in Rwanda and scaling‐up CVCT in 73 clinics in Zambia, we estimated HIV prevention cascade domains of motivation for use, access and effectiveness of CVCT as model parameters. Costs‐per‐couple tested were also estimated based on our previous studies. We used these parameters as well as country‐specific inputs to model the impact of CVCT over a five‐year time horizon in a previously developed and tested deterministic compartmental model. We consider six countries across Africa with varied HIV epidemics (South Africa, Zimbabwe, Kenya, Tanzania, Ivory Coast and Sierra Leone). Outcomes of interest were the proportion of HIV infections averted by CVCT, nationwide CVCT implementation costs and costs‐per‐HIV infection averted by CVCT. We applied 3%/year discounting to costs and outcomes. Univariate and Monte Carlo multivariate sensitivity analyses were conducted. Results: We estimated that CVCT could avert between 54% (Sierra Leone) and 62% (South Africa) of adult HIV infections. Average costs‐per‐HIV infection averted were lowest in Zimbabwe ($550) and highest in South Africa ($1272). Nationwide implementations would cost between 7% (Kenya) and 21% (Ivory Coast) of a country's President's Emergency Plan for AIDS Relief (PEPFAR) budget over five years. In sensitivity analyses, model outputs were most sensitive to estimates of cost‐per‐couple tested; the proportion of adults in heterosexual couples and HIV prevention cascade domains of CVCT motivation and access. Conclusions: Our model indicates that nationalized CVCT could prevent over half of adult HIV infections for 7% to 21% of the modelled countries' five‐year PEPFAR budgets. While other studies have indicated that CVCT motivation is high given locally relevant promotional and educational efforts, without required indicators, targets and dedicated budgets, access remains low. [ABSTRACT FROM AUTHOR]