EBOLA/EVD [to 18 July 2015]

EBOLA/EVD [to 18 July 2015]
Public Health Emergency of International Concern (PHEIC); “Threat to international peace and security” (UN Security Council)

Ebola Situation Report – 15 July 2015
:: There were 30 confirmed cases of Ebola virus disease (EVD) reported in the week to 12 July: 13 in Guinea, 3 in Liberia, and 14 in Sierra Leone. Although the total number of confirmed cases is the same as the previous week, there has been a shift in the foci of transmission. For the first time in several months, most cases were reported from Conakry and Freetown, the capitals of Guinea and Sierra Leone, respectively. All 9 of the cases reported from Conakry and all 10 of the cases reported from Freetown were either registered contacts of a previous case or have an established epidemiological link to a known chain of transmission. One of the 30 cases reported in the week to 12 July arose from a yet unknown source of infection. However, a substantial proportion of cases (7 of 30: 23%) continue to be identified as EVD-positive only after post-mortem testing. This suggests that although improvements to case investigation are increasing our understanding of chains of transmission, contact tracing, which aims to minimise transmission by identifying symptoms among contacts at the earliest stage of infection, is still a challenge in several areas…

:: There have been a total of 27,642 reported confirmed, probable, and suspected cases of EVD in Guinea, Liberia and Sierra Leone (figure 1, table 1) up to 12 July, with 11,261 reported deaths (this total includes reported deaths among probable and suspected cases, although outcomes for many cases are unknown). A total of 13 new confirmed cases were reported in Guinea, 3 in Liberia, and 14 in Sierra Leone in the week to 12 July…

WHO Stories from Countries
Ebola diaries: Lessons from previous Ebola outbreaks help with the response in Guinea
15 July 2015
Getting back to work: Training health staff for life and work after Ebola
14 July 2015

Bavarian Nordic Announces that the Oxford Vaccines Group has Initiated a Phase 2 Study of the Ebola Prime-Boost Vaccine Regimen Combining MVA-BN® Filo and Janssen’s AdVac® Technology
COPENHAGEN, Denmark, July 15, 2015 – Bavarian Nordic A/S (OMX: BAVA, OTC: BVNRY) announced today that the Oxford Vaccines Group has initiated a Phase 2 clinical study of the Ebola prime-boost vaccine regimen that combines Bavarian Nordic’s MVA-BN® Filo vaccine with the Ad26.ZEBOV vaccine from the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen). The first volunteers have received their initial vaccine dose.

Preliminary data from the first-in-human Phase 1 study, presented by Janssen in May to a U.S. Food & Drug Administration Advisory Committee, indicated that the prime-boost vaccine regimen is immunogenic, regardless of the order of vaccine administration, and only provoked temporary reactions normally expected from vaccination.

The Phase 2 study, to take place in the UK and France, is a randomized, placebo-controlled, multicenter trial evaluating the safety, tolerability and immunogenicity of the heterologous prime-boost regimen (Ad26.ZEBOV and MVA-BN-Filo) sponsored by Crucell Holland B.V., one of the Janssen Pharmaceutical Companies.

The study is part of the EBOVAC2 project, a collaborative program involving The University of Oxford, French Institute of Health and Medical Research (Inserm), London School of Hygiene & Tropical Medicine (LSHTM), La Centre Muraz (CM), Inserm Transfert (IT) and Janssen. The Innovative Medicines Initiative 2 Joint Undertaking is under grant agreement EBOVAC2 (grant no. 115861), part of the Ebola+ program launched in response to the Ebola virus disease outbreak.

The UK study site is led by the Oxford Vaccines Group, part of the University of Oxford, Department of Paediatrics. Additional sites in France will be coordinated by Inserm once all necessary approvals are received. In total, the studies will enroll 612 healthy adult volunteers in United Kingdom and France, who will be randomized into three cohorts, all receiving the Ad26.ZEBOV prime or placebo on day 1 and then the MVA-BN-Filo boost or placebo on days 29, 57 or 85. More information on the trial can be found at http://www.clinicaltrials.gov/ct2/show/NCT02416453.

A second Phase 2 study in 1,200 volunteers is planned to be initiated in Africa during third quarter of 2015.

Paul Chaplin, President & Chief Executive Officer of Bavarian Nordic, said: “We are pleased to report further progress in the clinical development of the prime-boost Ebola vaccine regimen which is being led by our partner Janssen. Vaccines play an essential role in outbreak situations, and both the clinical and the manufacturing experience we gain through this accelerated development represent an important piece of work in the combined efforts to ensure preparedness against Ebola, now and in the future.”…

Two new trials of Ebola vaccines begin in Europe and Africa
Reuters, LONDON, July 15 | By Kate Kelland
Two new Ebola vaccine trials began on Wednesday with volunteers in Britain, France and Senegal getting “prime-boost” immunisations developed by Bavarian Nordic, GlaxoSmithKline and Johnson & Johnson.
The mid-stage, or Phase II, trials are designed primarily to test the vaccines’ safety, but will also assess whether they provoke an immune response against the deadly virus…
…”The current Ebola outbreak has reinforced that speed of response is crucial,” said Egeruan Babatunde Imoukhuede, who is coordinating one of the trials in Senegal.
“Outbreak diseases spread quickly, so any vaccination approach must be able to keep up.”….
…The trial of the Bavarian Nordic and J&J prime-boost combination initially aims to recruit more than 600 healthy adult volunteers in Britain and France.
Bavarian said it hoped to launch another later phase of this trial in Africa later this year involving 1,200 volunteers, but other large clinical trials have recently been thwarted by the drop in case numbers.
Previously planned trials of GSK, Merck and J&J shots in West Africa have been struggling to recruit volunteers with enough exposure to Ebola to prove whether their vaccines are doing the job and preventing infection.
The second trial will be conducted in Senegal and uses two vaccines tested first in people at Oxford University’s Jenner Institute and being developed in a partnership with GSK. The first, based on a chimpanzee adenovirus, is designed to stimulate, or prime, an initial immune response, while the second is designed to boost that response…

Journal of Clinical Investigation
First published July 13, 2015
Aerosolized Ebola vaccine protects primates and elicits lung-resident T cell responses
Michelle Meyer1,2,3, Tania Garron1,2,3,4, Ndongala M. Lubaki1,2,3, Chad E. Mire2,3,4, Karla A. Fenton2,3,4, Curtis Klages2,3,5, Gene G. Olinger6, Thomas W. Geisbert2,3,4, Peter L. Collins7, and Alexander Bukreyev1,2,3,4,8
1Department of Pathology, 2Galveston National Laboratory, 3The University of Texas Medical Branch, 4Department of Microbiology and Immunology, and 5Animal Resources Center, Galveston, Texas, USA. 6Viral Pathogenesis and Immunology Branch, Virology Division, United States Army Institute for Infectious Diseases, Frederick, Maryland, USA., 7RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA., 8Sealy Center for Vaccine Development, Galveston, Texas, USA.
Direct delivery of aerosolized vaccines to the respiratory mucosa elicits both systemic and mucosal responses. This vaccine strategy has not been tested for Ebola virus (EBOV) or other hemorrhagic fever viruses. Here, we examined the immunogenicity and protective efficacy of an aerosolized human parainfluenza virus type 3–vectored vaccine that expresses the glycoprotein (GP) of EBOV (HPIV3/EboGP) delivered to the respiratory tract. Rhesus macaques were vaccinated with aerosolized HPIV3/EboGP, liquid HPIV3/EboGP, or an unrelated, intramuscular, Venezuelan equine encephalitis replicon vaccine expressing EBOV GP. Serum and mucosal samples from aerosolized HPIV3/EboGP recipients exhibited high EBOV-specific IgG, IgA, and neutralizing antibody titers, which exceeded or equaled titers observed in liquid recipients. The HPIV3/EboGP vaccine induced an EBOV-specific cellular response that was greatest in the lungs and yielded polyfunctional CD8+ T cells, including a subset that expressed CD103 (αE integrin), and CD4+ T helper cells that were predominately type 1. The magnitude of the CD4+ T cell response was greater in aerosol vaccinees. The HPIV3/EboGP vaccine produced a more robust cell-mediated and humoral immune response than the systemic replicon vaccine. Moreover, 1 aerosol HPIV3/EboGP dose conferred 100% protection to macaques exposed to EBOV. Aerosol vaccination represents a useful and feasible vaccination mode that can be implemented with ease in a filovirus disease outbreak situation.