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The safety and immunogenicity of the two-dose Ebola vaccine regimen MVA-BN-Filo, Ad26.ZEBOV, 14 days apart, was evaluated in people without HIV (PWOH) and living with HIV (PLWH). In this observer-blind, placebo-controlled, phase 2 trial, healthy adults were randomized (4:1) to receive MVA-BN-Filo (dose 1) and Ad26.ZEBOV (dose 2), or two doses of saline/placebo, administered intramuscularly 14 days apart. The primary endpoints were safety (adverse events (AEs)) and immunogenicity (Ebola virus (EBOV) glycoprotein-specific binding antibody responses). Among 75 participants (n = 50 PWOH; n = 25 PLWH), 37% were female, the mean age was 44 years, and 56% were Black/African American. AEs were generally mild/moderate, with no vaccine-related serious AEs. At 21 days post-dose 2, EBOV glycoprotein-specific binding antibody responder rates were 100% among PWOH and 95% among PLWH; geometric mean antibody concentrations were 6286 EU/mL (n = 36) and 2005 EU/mL (n = 19), respectively. A total of 45 neutralizing and other functional antibody responses were frequently observed. Ebola-specific CD4+ and CD8+ T-cell responses were polyfunctional and durable to at least 12 months post-dose 2. The regimen was well tolerated and generated robust, durable immune responses in PWOH and PLWH. Findings support continued evaluation of accelerated vaccine schedules for rapid deployment in populations at immediate risk. Trial registration: NCT02598388 (submitted 14 November 2015). [ABSTRACT FROM AUTHOR]

Background: Recent outbreaks between 2015-17 and production delays have led to a yellow fever vaccine shortage. Therefore, there is an urgent need for new yellow fever vaccines with improved production scalability. A next-generation live-attenuated yellow fever vaccine candidate (vYF), produced in a Vero cell line has shown similar immunogenicity to licensed yellow fever vaccines in preclinical studies. In this study, we aimed to report the safety and immunogenicity of vYF in human clinical trial participants., Methods: In this first in-human, phase 1 randomised, observer-blind, active-controlled, dose-ranging clinical trial conducted at a single centre in the USA (Walter Reed Army Institute of Research, Silver Spring, MD, USA), 72 healthy adults (aged 18-60 years), without a known history of flavivirus infection or vaccination were randomly assigned (1:1:1:1) using interactive response technology to receive one dose of either vYF at 4, 5 or 6 Log CCID 50 or the licensed YF-VAX (18 individuals per group). The primary outcomes were safety, neutralising antibody (NAb) titres through D180 post-vaccination in the per-protocol analysis set (comprised of yellow fever-naive participants who received their intended vaccine and provided a valid post-vaccination blood sample), and occurrence, and level of yellow fever viraemia in each vaccine group through D14 post-vaccination., Findings: All vYF doses had a safety and tolerability profile similar to YF-VAX. The most frequently reported solicited injection site reactions (vYF groups vs YF-VAX group) were pain (22% [12 of 54 participants, 95% CI 12-36] vs 28% [five of 18 participants, 10-54]), and erythema (13% [seven of 54 participants, 5-25] vs 39% [seven of 18 participants, 17-64]), with headache (32% [17 of 54 participants, 20-46] vs 44% [eight of 18 participants, 22-69]) and malaise (26% [14 of 54 participants, 15-40] vs 33% [six of 18 participants, 13-59]) as the most frequently reported solicited systemic reactions. One grade 3 solicited reaction (erythema) reported in the YF-VAX group resolved spontaneously. No serious unsolicited adverse events or deaths were reported. Viraemia was transiently detected in 50 participants between D4 and D10 in all groups and was observed in more participants or for a longer time in the vYF 6 Log CCID 50 and YF-VAX groups. All yellow fever-naive vaccine recipients across the study groups seroconverted yielding four-fold increase from baseline in yellow fever NAb titres measured by yellow fever microneutralisation assay by D28 and were seroprotected with yellow fever NAb titres of at least 10 [1/dil]). Overall, 100% (18 of 18 participants, 95% CI 82-100), 89% (16 participants, 65-99), 100% (18 participants, 82-100), and 94% (17 participants, 73-100) of participants in the vYF 4 Log, vYF 5 Log, vYF 6 Log CCID 50 groups, and YF-VAX group, respectively, remained seroprotected through D180., Interpretation: vYF has a similar safety and immunogenicity profile to YF-VAX. In general, the vYF 5 Log CCID 50 dose appeared to show optimal viraemia, safety, and immunogenicity, and was chosen for subsequent development., Funding: Sanofi., Competing Interests: Declaration of interests A-MM, HA, YW, ARP, VD, NM, MV, and EF are Sanofi employees and hold shares and stock options in the company. KM and PTS were employed by the Walter Reed Army Institute of Research at the time of this study. MM, BO-S, ES, MFA, APP, BO, MNM, KSK, MEM, IG, MEG, JMD, MAK, MJH, CEL, JNH, SAP, and MLR received funds from Sanofi through their institutions to support their work in the VYF01 trial (NCT04142086)., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

In December 2019, an outbreak of pneumonia caused by a novel coronavirus, severe acute respiratory syndrome (SARS)-CoV-2, occurred in Wuhan city, Hubei province, China.1 South Korea saw its first confirmed Coronavirus Disease 2019 (COVID-19) case on January 20, 2020, when an infected woman from Wuhan, China arrived in S. Korea via Incheon International Airport.1 By mid-February, SARS-CoV-2 was rapidly spreading in the southern city of Daegu, S. Korea in proximity to three US Forces Korea (USFK) military installations. COVID-19 cases continued to increase during the following weeks, reaching a peak of nearly 1,000 confirmed cases per day by the end of February. As cases surged dramatically, over 28,000 USFK service members, family members, and Department of Defense (DoD) employees were at a risk of exposure to COVID-19. On February 24, clinicians diagnosed the first confirmed case in the USFK population, a 61 year-old widow of a retired service member. This individual, who experienced a mild illness, was the spouse of a retired US military veteran living in S. Korea. The retiree and his spouse both had access to military posts in S. Korea, and the spouse tested positive after she had been on one of the military bases in Area IV (Figure 1). The following day, USFK reported its first confirmed case in a service member, which was the triggering event for the 1st Area Medical Laboratory (AML) to deploy to S. Korea.