Extract from GACVS meeting of 4-5 December 2019, published in the WHO Weekly Epidemiological Record of 24 January 2020

rVSV-ZEBOV vaccine

On 1 August 2018, the Ministry of Health of the Democratic Republic of the Congo (DRC) reported an outbreak of Ebola virus disease (EVD) in North Kivu province, which is continuing in eastern DRC, with a total of 3303 cases of EVD (3185 confirmed) and 2199 deaths as of 24 November 2019.⁵ Merck's rVSV-ZEBOV-GP vaccine, which was recently conditionally approved by the European Commission and pre-qualified by WHO, is used according to the SAGE recommendation for expanded access in a ring vaccination strategy.⁶ GACVS was provided with information on safety from current vaccination work in the DRC and other WHO-sponsored studies. In DRC, about 250 000 people received a single dose of the rVSV-ZEBOV-GP vaccine under the expanded access protocol, including pregnant women and infants <1 year of age. Follow-up for solicited local and systemic adverse events (AEs) was done 30 min post-vaccination and on days 3 and 21. Phase 1 of the study was conducted from August 2018 to June 2019, when people were given 5 x 10⁷ plaque-forming units (PFU) of the vaccine. Phase 2 was conducted between June and September 2019, when people received 2 x 10⁷ PFU, i.e. an adjusted dose similar to that administered in a ring vaccination trial in Guinea in 2014-2015. The AEs that occurred in adults within the first 3 days post-vaccination (n= 121 770) given 5 x 10⁷ PFU/dose in North Kivu were reported to be mild (>90%), headache, fatigue and arthralgia being the most commonly reported.

AEs that occurred during the first 3 days in people given the vaccine in Uganda (n=8060), South Sudan (n=3048) and Rwanda (n=2732) and in adults 15–21 days post vaccination in the areas of Guinea forestière (n=1207), DRC Equateur (n=1535), Guinea Proches (n=2114), Uganda (n=8060), South Sudan (n=3048) and Rwanda (n=2732) were similar; however, follow-up and data collection in these regions varied. The most commonly recorded AEs during the first 3 days post-vaccination in children aged 6–17 years in DRC North Kivu (n=27 952), Guinea forestière (n=303) and DRC Equateur (n=205) were headache, fatigue and arthralgia. There were insufficient data on AEs in children aged 6–17 years during the 4–14-day and 15–21-day follow-up periods. AEs in children aged 1–5 years (n=10 731) in North Kivu had a similar profile. GACVS noted that the data recorded on AEs in children were insufficient, particularly for those aged 6–11 months (n=1141) vaccinated with 2 x 10⁷ PFU/dose; however, no overt safety concerns were identified. Solicited AEs were provided by 1120 pregnant women who received 2 x 10⁷ PFU of the vaccine in North Kivu. Arthralgia, diarrhoea, fatigue, headache, vomiting, injection site pain, muscle pain and myalgia were reported, which were mostly mild to moderate. Pregnancy outcomes were available for 271 women, with 257 healthy births, 10 stillbirths and 3 spontaneous abortions. There was 1 maternal death due to EVD. GACVS acknowledged the limitations in follow-up and data recording on safety because of the large number of people vaccinated under challenging operational conditions, and they applauded WHO’s work. GACVS noted that, overall, there appeared to be no new untoward AEs, and the safety data suggest that the vaccine is well tolerated by adults and children. The data presented confirmed the safety profile of the vaccine in people who participated in the Ebola ça Suffit trial.

Ad26.ZEBOV/MVA-BN-Filo vaccine

Product characteristics and nonclinical and clinical data for the Ad26.ZEBOV/MVA-BN-Filo vaccine were reviewed in the context of the viral vector templates and clinical safety data presented by Janssen. The effectiveness of the vaccine was determined from immunogenicity in humans and challenge and protection studies in non-human primates. The vaccine is administered in 2 doses, the first consisting of Ad26.ZEBOV at 5 x 10¹⁰ virus particles, followed by a dose of MVA-BN-Filo at 1 x 10⁸ infectious units 56 days later. Vaccine safety is being evaluated in 12 ongoing and completed phase 1, 2 and 3 studies in Africa, Europe and the USA. Unblinded, pooled data on safety for healthy and HIV-infected adults (n= 3516) who received the vaccines on a 0/28, 0/84 or 0/56 schedule indicated that solicited and unsolicited local and systemic AEs were mild to moderate and of short duration. The most frequently reported local solicited AE was injection site pain, and the most frequently reported systemic solicited AE was fatigue. The incidence of grade 3 fever (>39 °C) within 7 days of vaccination was low (1.4%). No excess of serious AEs, including potential neuro-inflammatory events, was reported within 28 days after dosing. Safety data from completed and ongoing studies in >6500 adults and safety data from other Ad26-based (>8000 people) and MVA-BN-based vaccine (>14 500 people) programmes did not raise concern. Unblinded data for 649 children who received the recommended dose and regimen at ages 12–17 years (n=253), 4–11 years (n=252) and 1–3 years (n=144) indicated mild-to-moderate AEs, with a low rate of grade 3 fever within 7 days of vaccination (<1.5%). Serious AEs occurred in 13 children (2%) in the active group and in 3 children (1.6%) in the control group. All these AEs were infections or complications of malaria, with 1 second-degree burn in the control group. No concern about safety was identified in children aged 1–17 years. In 66 unintended pregnancies, there was no apparent pattern of AEs and no safety concern. GACVS noted that the data presented suggest that the vaccine is well tolerated and does not raise any safety concerns but that the data for special populations and children are limited.

GACVS reviewed the standardized template developed by the Brighton Collaboration Viral Vector Vaccines Safety working group for the replication-incompetent Ad26 viral vector and the modified vaccinia Ankara (MVA) vector. Aspects of replication-incompetent Ad26 viral vectors of special interest for vaccine development include a low probability of regaining replication competence, limited impact of vector immunity, low risk of integration into the host genome, vector stability, limited shedding and unlikely transmission. The Ad26.ZEBOV vaccine consists of the replication-incompetent Ad26 vector containing the glycoprotein gene of Ebola virus at the site of the E1 deletion. The vector is replication-incompetent because of deletion of early region 1 and partial deletion of early region 3. The Ad26 vector is not toxic in animal models and has limited biodistribution, as the vector is detected mainly at the injection site. Vaccines based on the Ad26 platform administered to >8000 participants had an acceptable safety profile and induced potent humoral and cellular immune responses.

Aspects of MVA-BN viral vectors of special interest for vaccine development include an inability to replicate in human cell lines, a very low risk of reversion to wild type, the ability to accommodate multigenic inserts, low risk of integration into the host genome, vector stability, negligible potential for shedding and unlikely transmission. The MVA-BN vector was derived from the vaccinia virus strain Ankara by serial passage in chicken embryo fibroblasts, further multiple passaging in eggs and plaque purification. The vector has 6 major deletions, including immune evasion genes, structural proteins and host interaction protein genes. Protein sequences for the glycoprotein from Ebola virus Mayinga, Sudan virus Gulu and Marburg virus Musoke and nucleoprotein from Tai-Forest virus were inserted into the MVA-BN non-coding regions. The MVA-BN vector was safe when administered to the animal models studied, and it is not biodistributed, as the vector is detected mainly at the injection site. Recombinant MVA BN vaccines induce an immune response in individuals previously vaccinated against smallpox. The MVA-BN vector has been administered to >14 500 both healthy and immunocompromised individuals in 22 completed clinical trials with the backbone vector and in >20 trials with recombinant constructs, in which it has shown a favourable safety profile and induction of a strong vaccinia-specific immune response.

GACVS noted that, overall, the safety profiles of both the rVSV-ZEBOV-GP vaccine and the Ad26.ZEBOV/MVA-BN-Filo vaccine constructs are reassuring and that these vaccines represent breakthroughs as medical countermeasures against EVD. GACVS recommended that any review of the safety of additional vector-based Ebola virus vaccines should be based on the Brighton Collaboration vector template, as it offers a structured approach to evaluating safety.

⁵ Ebola virus disease. Democratic Republic of the Congo. External situation report 69. Brazzaville; WHO Regional Office for Africa; 2019 (https://apps.who.int/iris/rest/bitstreams/1261934/retrieve, accessed December 2019).

⁶ WHO Strategic Advisory Group of Experts (SAGE) on Immunization. Interim recommendations on vaccination against Ebola virus disease (EVD). Geneva: World Health organization; 2019 (https://www.who.int/immunization/policy/position_papers/interim_ebola_recommendations_may_2019.pdf?ua=1, accessed December 2019).

Report of GACVS meeting of 4-5 December 2019, published in the WHO Weekly Epidemiological Record of 24 January 2020

On 1 August 2018, the Ministry of Health of the Democratic Republic of the Congo (DRC) reported an outbreak of Ebola virus disease (EVD) in North Kivu province. As of 4 June 2019, a total of 2008 EVD cases, including 1832 confirmed cases and 1346 deaths had been recorded. SAGE has recommended extending ring vaccination with the rVSV-ZEBOV vaccine should an EVD outbreak occur. This vaccine was used in a ring vaccination study conducted in Guinea during the outbreak of EVD in West Africa in 2015, with high efficacy. It is currently the only vaccine for which data on clinical effectiveness are available.

Nevertheless, GACVS considered use of other licensed and investigational Ebola vaccines. There are currently 2 licensed Ebola vaccines: a single-dose Ad5-EBOV vaccine in China and a 2-dose rVSV/Ad5 vaccine licensed in the Russian Federation “for emergency use”. In addition, there are 2 investigational vaccines, the rVSV-ZEBOV vaccine made by Merck and the Ad26.ZEBOV/MVA-BN-Filo vaccine by Janssen.

GACVS members were presented with preliminary information on these vaccines, including their characteristics, source of viral strains, dose, schedule, storage conditions, nonclinical and clinical development and licensure status. The Ad5-EBOV (China) and the rVSV/Ad5 vectored vaccine (Russian Federation) “for emergency use” were licensed on the basis of tests in animal models and data on human immunogenicity from phase 1 and 2 clinical trials, which included studies in African populations. The effectiveness of the Ad26.ZEBOV/MVA-BN-Filo vaccine made by Janssen is based on studies in non-human primates in phase 1 and 2 clinical safety and immunogenicity trials; a phase 3 study is planned. Data on the safety of this vaccine are available for about 4000 people. Data on use of any of the 3 vaccines in elderly or immune-compromised people, children and pregnant or lactating women are not yet available.

The product characteristics and nonclinical and clinical data available for the rVSV-ZEBOV made by Merck were reviewed in the context of the viral vector template, clinical safety data presented by Merck and data from studies of clinical efficacy. In brief, the rVSV-ZEBOV was evaluated in several phase 2 and 3 clinical studies in over 15 000 people. Interim data on the impact of the ring vaccination strategy used during the current outbreak in the DRC were presented, which confirmed high vaccine efficacy. The safety of the vaccine is being followed up in all the recipients in this ring vaccination study 30 minutes and 3 and 21 days after vaccination. If enrolment of infants and pregnant women is approved, safety will be followed up on day 21 after vaccination for infants aged 6–11 months and pregnant women and also at delivery for the pregnant women; their offspring will not be followed up. As of 5 June 2019, more than 130 000 individuals in the DRC had consented and were vaccinated. Of the 228 serious adverse events (SAEs) identified between 7 August 2018 and 5 June 2019), only a few, including 1 case of anaphylaxis, were attributed to the vaccine.

The GACVS was presented with an overview of the standard template for the recombinant vesicular stomatitis virus (rVSV) vector developed by the Brighton Collaboration Viral Vector Vaccines Safety Working group, which is being explored as a platform for multiple vaccines. The rVSV causes self-limited disease in horses, pigs and cattle, but humans are generally asymptomatic. Other advantages include a low prevalence of vector immunity, the inability of viral RNA to integrate and the ability to express large foreign genes. The rVSV-ZEBOV vaccine constitutes the live, replication-competent VSV vector with the VSV glycoprotein G gene replaced by the glycoprotein gene of ZEBOV. Deletion of the G protein, the principal Ebola virus virulence factor, causes attenuation and also removes the primary target for anti-vector immunity. Preclinical data on the rVSV-ZEBOV showed no toxic effects in mice, rats or non-human primates and no neurovirulence in non-human primates; however, rVSV-ZEBOV is neurotropic in neonatal mice. VSV and rVSV-ZEBOV are highly sensitive to interferon and are relatively thermostable; associated viraemia occurs for the first 24–72 hours but is rarely detectable by 72 hours. The rVSV-ZEBOV elicits innate immune responses and adaptive immune responses within 7–14 days.

Merck updated the clinical safety profile of the investigational rVSV-ZEBOV-GP (V920) vaccine. The safety of the vaccine was evaluated in 8 phase 1 clinical trials in various countries and populations and in 5 phase 2 and 3 studies in Liberia (PREVAIL), Sierra Leone (STRIVE), Guinea (Ebola Ça Suffit! and Frontline Workers) and in Canada, Spain and the USA. Data on its safety are available for 15 996 people, including 234 children (> 6 months to < 18 years), 536 elderly people (> 65 years), 261 pregnant women and 22 HIV-positive patients. The most common local reactions were pain (70.3%), swelling (16.7%) and erythema (13.7%), which were limited in duration and of mild to moderate severity. Systemic reactions that were more common in vaccinated people than in recipients of placebo included headache, pyrexia, myalgia, fatigue, arthralgia, nausea, chills, arthritis, rash, hyperhidrosis, abdominal pain and rare cases of anaphylaxis. The results of an integrated analysis of the double-blinded trials showed SAEs in 3.4% of vaccine recipients and 7.8% of placebo recipients (1-year follow up), the most common reported SAE in the vaccine group being malaria, which was reported in 1.5% of those receiving the vaccine and 5.6% receiving placebo. Arthralgia of short duration occurred in up to 50% of vaccinated people during the first 14 days after vaccination. In blinded trials, the median time to onset of arthritis events was approximately 10 days, and the mean duration was 6 days; most cases were mild to moderate, although a few persisted for months to years. Vesicular lesions and oral ulcers occurred in a few people. Among the 261 pregnant women who received the vaccine in the trials in Sierra Leone, the frequency of pregnancy loss was higher in the group that was vaccinated immediately than in the deferred crossover or unvaccinated group; the reasons for the differences are not clear. Although these findings are of concern, their interpretation is difficult, as there were few exposures and limited data on the outcomes of the pregnancies, and the timing of vaccination in relation to gestational age was difficult to establish. Reliable background rates of pregnancy and neonatal outcomes are also lacking. Data on safety in the 234 children (ages 6 to <18 years) enrolled in 2 studies suggest that the adverse events reported were in general consistent with those observed in adults. Post-vaccination viraemia was detected more often in children than adults. Viral shedding in saliva and urine was also reported more frequently in children (71.8% overall versus 2% overall); however, no data are yet available on secondary transmission.

Data on the safety and efficacy of the rVSV-ZEBOV vaccine in infants (<1 year) are not available, and there are no data on lactating women. A clinical study with children aged 1–17 years and a study in HIV-positive people are under way. GACVS noted that more data are needed on the pregnancy outcomes. Concern was expressed about the possible implications of viral shedding and viraemia, the latter especially in infants. For the review of the safety of Ebola virus vaccines planned for the GACVS meeting in December 2019, it was decided that the vector template should be used, as it offers a structured approach to evaluating the safety of the vector-based Ebola virus vaccines. Additional information on safety from current vaccination initiatives in the DRC and, if available, from additional clinical trials with the V920 vaccine and other Ebola virus vaccines should be made available for review by the GACVS.

Report of GACVS meeting of 5-6 June 2019, published in the WHO Weekly Epidemiological Record of 12 July 2019

In response to the unprecedented Ebola outbreak in West Africa, in August 2014 WHO called for accelerated production of preventive vaccines that could potentially help control the outbreak. Criteria proposed for selection of vaccine candidates included prior demonstration of full protection against lethal Ebola virus challenge in non-human primates and production in facilities that met good manufacturing practices. Two vaccines, both based on insertion of an Ebola virus glycoprotein gene into a viral vector, had entered Phase 1 development by September–October 2014. By early 2015 Phase 2/3 studies with both products were under way in highly affected countries of West Africa.⁸

One candidate vaccine, developed by the US National Institute of Allergy and Infectious Diseases and GlaxoSmithKline plc, uses a replication incompetent chimpanzee adenovirus 3 (ChAd3) vector with the E1 and E4 genes deleted. An Ebola virus Zaire (EBO-Z) glycoprotein (GP) gene cassette has been inserted in place of the E1 deleted region. Another candidate vaccine, developed by the Public Health Agency of Canada and subsequently licensed to NewLink and Merck & Co., Inc., uses an attenuated vesicular stomatitis virus (VSV) as the vaccine vector. The VSV G gene has been deleted and replaced with a EBO-Z GP expression cassette. The resulting recombinant virus is attenuated but remains replication competent.

Phase 1 studies of the ChAd3 vaccine began in September 2014 with limited data already published.^{9, 10} A total number of 271 healthy adults were vaccinated with ChAd3-EBO-Z in Phase 1 studies in the United States, the United Kingdom, Mali and Switzerland, with doses ranging from 1010 to 1011 viral particles. An additional Phase 1 study including 2 arms testing monovalent ChAd3-EBO-Z (n=34) was undertaken in Uganda. Based on safety and immunogenicity data from Phase 1 studies, the 1011 viral particle dose was selected for further clinical testing. Phase 2 studies in healthy adults and in children are planned in West African countries adjacent to the current outbreak zone. A Phase 2/3 study, in collaboration with the U.S. National Institutes of Health, was begun in Liberia in February 2015 but safety data were not available at the time of the GACVS meeting.

In the Phase 1 studies, dose-related reactogenicity was observed, with injection-site pain and fever mainly occurring within the first 24 hours after vaccination. In most recipients, fever resolved within 24 hours. Transient clinically non-significant reductions in lymphocyte and platelet counts were observed, as is seen with many live virus vaccines. No serious adverse events ascribed to the vaccine or other unexpected serious adverse reactions were found.

Phase 1 studies of the rVSV-ZEBOV-GP vaccine began in October 2014 with limited data already published.^{11, 12} In total, 248 volunteers were vaccinated across 7 studies in the United States, Switzerland, Germany, Gabon, Kenya and Canada; enrollment for all studies was completed by May 2015. Collection of long-term safety and immunogenicity data from these studies is ongoing. A Phase 1b dose-ranging study, with 256 volunteers receiving doses of rVSV-ZEBOV ranging from 3 x 10³ to 3 x 10⁶ or placebo (n=74) was initiated in the United States in December 2014.

In those studies, pain at the injection site was common as were systemic symptoms including fever, malaise, and “flu-like symptoms” (chills, myalgia, headaches and fatigue) were common after vaccination and generally lasted 1 to 3 days. Administration of rVSV vaccine results in viraemia that is detectable by polymerase chain reaction (PCR) during the first and sometimes second week after vaccination, with a peak found on day 2. Vaccine virus was detected by PCR in urine and saliva in less than 10% of subjects. No vaccine-related serious adverse reactions have been reported to date from Phase 1 or 1b studies. Arthralgia, arthritis, dermatitis, rash and cutaneous vasculitis were reported, with varying frequency between study sites, in the 2nd week following vaccination; these reactions are associated with vaccine virus replication in the joints and the skin as demonstrated by PCR testing of specimens collected from those sites and evidence of local viral gene expression documented by immunohistochemistry. In subjects with arthritis, pain generally lasted 2–3 weeks, but occasionally more than 3 months. Joint reactions did not occur more frequently with higher doses of vaccine, but were more common among older subjects. A small number of skin vesicles and mouth ulcers were also observed and limited data did not indicate that virus had been detected by PCR. Transient, non-clinically significant reductions in neutrophil and lymphocyte counts were found in some recipients in the first few days following vaccination.

The rVSV vaccine is currently being tested in Phase 2/3 studies in Liberia, Guinea, and Sierra Leone; safety data are not yet available from those studies. Additional assessment of joint and skin events is planned in upcoming clinical studies.

Safety data from Phase 1 studies of both ChAd3 and rVSV vaccines indicate an acceptable safety profile in healthy adults. Ongoing studies will provide additional experience in adults, and will allow more extensive assessment of safety. No data are currently available regarding the safety of these vaccines in subjects with underlying disease or medical conditions. There are also no data regarding the safety of these products in paediatric and pregnant subjects.

⁸ In addition to the two candidate vaccines described above, more recently two other Ebola vaccine programmes have met the initially proposed pre-clinical trial criteria. These are a heterologous combination of two replication deficient recombinant vectors: human adenovirus 26 and modified vaccinia virus Ankara, both expressing ZEBOV GP (Johnson & Johnson) and a baculovirus expressing recombinant ZEBOV GP nanoparticle vaccine (Novavax). Both of these programmes have initiated Phase 1 trials; currently neither programme has clinical trial data available from sub-Saharan Africa.

⁹ Ledgerwood JE, De Zure AD, Stanley DA et al. Chimpanzee adenovirus vector vaccine – preliminary report. N Engl J Med 2014 Nov 26. [EPUB ahead of print].

¹⁰ Rampling T1, Ewer K, Bowyer G et al. A monovalent chimpanzee adenovirus Ebola vaccine - Preliminary report. N Engl J Med. 2015 Jan 28. [EPUB ahead of print].

¹¹ Regules JA, Beigel JH, Paolino KM et al. A recombinant vesicular stomatitis virus Ebola vaccine - Preliminary report. N Engl J Med. 2015 Apr 1. [EPUB ahead of print].

¹² Agnandji ST, Huttner A, Zinser ME et al. Phase 1 trials of rVSV Ebola vaccine in Africa and Europe - Preliminary report. N Engl J Med. 2015 Apr 1. [EPUB ahead of print].

Full report of GACVS meeting of 10-11 June 2015, published in the WHO Weekly Epidemiological Record of 17 July 2015

WHO actively supports and plays a key role in the coordination of vaccine development. Two Ebola virus vaccines are currently undergoing phase 1 clinical trials: ChAd3-EBO-Z (GSK Biologicals/NIAID) and rVSV-ZEBOV (NewLink/Merck). Timelines for the availability of phase 1 data and key milestones for the phase 2/3 testing were presented. Phase 3 trials for Ebola vaccines could start in early 2015 with initial safety data possibly available by June 2015. Despite the need for an accelerated vaccine development programme, the essential steps to ensure vaccine safety and quality are being followed. Vaccine quality is being overseen by good manufacturing practices committees. Ethics committees, data safety monitoring boards and other scientific boards are overseeing all trials and focusing particularly on the need for high quality of the data.

(1) The ChAd3-EBO-Z vaccine consists of a recombinant replication-defective Chimpanzee adenovirus type 3 (ChAd3) derived vector encoding the Ebola virus Zaire (EBOV-Z) glycoprotein. Preclinical data showed acute immunity against EBOV-Z with a single dose and durable immunity with a prime-boost regimen. Results were presented for the phase 1 trial VRC 207 (site: USA; product: bivalent 2x10¹⁰ and 2x10¹¹ particle units; phase 1; n=20; start date: 2 September 2014).⁷ Safety and reactogenicity data in the 2x1011 particle units group included 2/10 subjects reporting fever (1 was of grade 3), 3 presenting transient asymptomatic neutropenia or leukopenia and 2 presenting asymptomatic prolonged aPTT (consistent with an in-vitro effect on the laboratory assay). No safety concerns were identified by the investigators at the highest dose in this phase 1 study. A dose-dependent immune response was demonstrated at weeks 2 and 4.

On-going studies include a monovalent phase 1 study (n=60) in the United Kingdom (EBL01), a phase 1 study (n=91); in Mali (CVD-1000), a bivalent 2-dose study (n=100+10 with booster dose); a monovalent phase 2a study (n=120) in Switzerland (Cad3-EBOZ Lau); and a monovalent study (n=20) in USA (VRC 207 part 2). Two phase 1 and 1a trials are planned in Mali and Uganda.

(2) The rVSV-ZEBOV vaccine is a recombinant vesicular stomatitis virus with the G protein of the VSV envelope deleted and replaced by the G protein of the EBOV-Z. As at 28 November 2014, a total of 69 subjects had received 3x10⁶ or 5x10⁷ particle units vaccine doses in several phase 1 trials in progress (Gabon, Germany, Kenya, Switzerland, USA – 2 sites). The reactogenicity profile was presented as being acceptable, without serious adverse events. Systemic adverse events at grade 1–2 have included fever, fatigue, myalgia, headache and transient decreased white blood cell counts. These were generally seen during the first 3 days post administration. The percentage of fever varied between study sites. There was minimal evidence of vaccine virus shedding.

Initial data have not elicited any major safety concerns with respect to either product. However, additional data are needed in order to assess any rare or delayed reactions as well as risk in particular population subgroups such as immune deficient individuals, pregnant women and patients with chronic medical conditions.

GACVS considered the role of various stakeholders in the development of Ebola virus vaccines, in particular agencies involved with the assessment of clinical trial data, the Strategic Advisory Group of experts on immunization (SAGE) for providing recommendations about vaccine use and implementation strategies, and GACVS for risk assessment. A GACVS subgroup will be set up in order to promptly address new evidence and assess risks related to Ebola virus vaccines.

⁷Ledgerwood et al. Chimpanzee adenovirus vector Ebola vaccine — Preliminary Report. NEJM 2014 e-pub 26 November

Full report of GACVS meeting of 3-4 December 2014, published in the WHO Weekly Epidemiological Record of 23 January 2015