Journal Article > ResearchFull Text
Vaccines. 2024 July 26; Volume 12 (Issue 8); 828.; DOI:10.3390/vaccines12080828
Choi EM, Kasonia K, Kavunga-Membo H, Mukadi-Bamuleka D, Soumah A, et al.
Vaccines. 2024 July 26; Volume 12 (Issue 8); 828.; DOI:10.3390/vaccines12080828
During the 2018–2020 Ebola virus disease outbreak in Democratic Republic of the Congo, a phase 3 trial of the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine (DRC-EB-001) commenced in Goma, with participants being offered the two-dose regimen given 56 days apart. Suspension of trial activities in 2020 due to the COVID-19 pandemic led to some participants receiving a late dose 2 outside the planned interval. Blood samples were collected from adults, adolescents, and children prior to their delayed dose 2 vaccination and 21 days after, and tested for IgG binding antibodies against Ebola virus glycoprotein using the Filovirus Animal Nonclinical Group (FANG) ELISA. Results from 133 participants showed a median two-dose interval of 9.3 months. The pre-dose 2 antibody geometric mean concentration (GMC) was 217 ELISA Units (EU)/mL (95% CI 157; 301) in adults, 378 EU/mL (281; 510) in adolescents, and 558 EU/mL (471; 661) in children. At 21 days post-dose 2, the GMC increased to 22,194 EU/mL (16,726; 29,449) in adults, 37,896 EU/mL (29,985; 47,893) in adolescents, and 34,652 EU/mL (27,906; 43,028) in children. Participants receiving a delayed dose 2 had a higher GMC at 21 days post-dose 2 than those who received a standard 56-day regimen in other African trials, but similar to those who received the regimen with an extended interval.
Journal Article > ResearchFull Text
PLOS Med. 2016 March 1; Volume 13 (Issue 3); DOI:10.1371/journal.pmed.1001967
Sissoko D, Laouenan C, Folkesson E, M’Lebing A, Beavogui A, et al.
PLOS Med. 2016 March 1; Volume 13 (Issue 3); DOI:10.1371/journal.pmed.1001967
Ebola virus disease (EVD) is a highly lethal condition for which no specific treatment has proven efficacy. In September 2014, while the Ebola outbreak was at its peak, the World Health Organization released a short list of drugs suitable for EVD research. Favipiravir, an antiviral developed for the treatment of severe influenza, was one of these. In late 2014, the conditions for starting a randomized Ebola trial were not fulfilled for two reasons. One was the perception that, given the high number of patients presenting simultaneously and the very high mortality rate of the disease, it was ethically unacceptable to allocate patients from within the same family or village to receive or not receive an experimental drug, using a randomization process impossible to understand by very sick patients. The other was that, in the context of rumors and distrust of Ebola treatment centers, using a randomized design at the outset might lead even more patients to refuse to seek care. Therefore, we chose to conduct a multicenter non-randomized trial, in which all patients would receive favipiravir along with standardized care. The objectives of the trial were to test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak, and to collect data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with EVD. The trial was not aimed at directly informing future guidelines on Ebola treatment but at quickly gathering standardized preliminary data to optimize the design of future studies.
Journal Article > ResearchFull Text
Vaccine. 2020 June 1; Volume 38 (Issue 31); DOI:10.1016/j.vaccine.2020.04.066
Boum Y II, Juan-Giner A, Hitchings MD, Soumah A, Strecker T, et al.
Vaccine. 2020 June 1; Volume 38 (Issue 31); DOI:10.1016/j.vaccine.2020.04.066
Background
As part of a Phase III trial with the Ebola vaccine rVSVΔG-ZEBOV-GP in Guinea, we invited frontline workers (FLWs) to participate in a sub-study to provide additional information on the immunogenicity of the vaccine.
Methods
We conducted an open‐label, non‐randomized, single-arm immunogenicity evaluation of one dose of rVSVΔG-ZEBOV-GP among healthy FLWs in Guinea. FLWs who refused vaccination were offered to participate as a control group. We followed participants for 84 days with a subset followed-up for 180 days. The primary endpoint was immune response, as measured by ELISA for ZEBOV-glycoprotein–specific antibodies (ELISA-GP) at 28 days. We also conducted neutralization, whole virion ELISA and enzyme-linked immunospot (ELISPOT) assay for cellular response.
Results
A total of 1172 participants received one dose of vaccine and were followed-up for 84 days, among them 114 participants were followed-up for 180 days. Additionally, 99 participants were included in the control group and followed up for 180 days. Overall, 86.4% (95% CI 84.1–88.4) of vaccinated participants seroresponded at 28 days post-vaccination (ELISA- GP) with 65% of these seroresponding at 14 days post-vaccination. Among those who seroresponded at 28 days, 90.7% (95% CI 82.0–95.4) were still seropositive at 180 days. The proportion of seropositivity in the unvaccinated group was 0.0% (95% CI 0.0–3.8) at 28 days and 5.4% (95% CI 2.1–13.1) at 180 days post-vaccination. We found weak correlation between ELISA-GP and neutralization at baseline but significant pairwise correlation at 28 days post-vaccination. Among samples analysed for cellular response, only 1 (2.2%) exhibited responses towards the Zaire Ebola glycoprotein (Ebola GP ≥ 10) at baseline, 10 (13.5%) at day 28 post-vaccination and 27 (48.2%) at Day 180.
Conclusions
We found one dose of rVSVΔG-ZEBOV-GP to be highly immunogenic at 28- and 180-days post vaccination among frontline workers in Guinea. We also found a cellular response that increased with time.
As part of a Phase III trial with the Ebola vaccine rVSVΔG-ZEBOV-GP in Guinea, we invited frontline workers (FLWs) to participate in a sub-study to provide additional information on the immunogenicity of the vaccine.
Methods
We conducted an open‐label, non‐randomized, single-arm immunogenicity evaluation of one dose of rVSVΔG-ZEBOV-GP among healthy FLWs in Guinea. FLWs who refused vaccination were offered to participate as a control group. We followed participants for 84 days with a subset followed-up for 180 days. The primary endpoint was immune response, as measured by ELISA for ZEBOV-glycoprotein–specific antibodies (ELISA-GP) at 28 days. We also conducted neutralization, whole virion ELISA and enzyme-linked immunospot (ELISPOT) assay for cellular response.
Results
A total of 1172 participants received one dose of vaccine and were followed-up for 84 days, among them 114 participants were followed-up for 180 days. Additionally, 99 participants were included in the control group and followed up for 180 days. Overall, 86.4% (95% CI 84.1–88.4) of vaccinated participants seroresponded at 28 days post-vaccination (ELISA- GP) with 65% of these seroresponding at 14 days post-vaccination. Among those who seroresponded at 28 days, 90.7% (95% CI 82.0–95.4) were still seropositive at 180 days. The proportion of seropositivity in the unvaccinated group was 0.0% (95% CI 0.0–3.8) at 28 days and 5.4% (95% CI 2.1–13.1) at 180 days post-vaccination. We found weak correlation between ELISA-GP and neutralization at baseline but significant pairwise correlation at 28 days post-vaccination. Among samples analysed for cellular response, only 1 (2.2%) exhibited responses towards the Zaire Ebola glycoprotein (Ebola GP ≥ 10) at baseline, 10 (13.5%) at day 28 post-vaccination and 27 (48.2%) at Day 180.
Conclusions
We found one dose of rVSVΔG-ZEBOV-GP to be highly immunogenic at 28- and 180-days post vaccination among frontline workers in Guinea. We also found a cellular response that increased with time.
Journal Article > ResearchFull Text
Vaccine. 2019 November 15; Volume 37 (Issue 48); 7165-7170.; DOI:10.1016/j.vaccine.2019.09.094
Grantz KH, Claudot P, Kambala M, Kouyate M, Soumah A, et al.
Vaccine. 2019 November 15; Volume 37 (Issue 48); 7165-7170.; DOI:10.1016/j.vaccine.2019.09.094
BACKGROUND
Alongside the clinical aspects of the immunogenicity and safety trial of an Ebola vaccine deployed among front-line workers, a qualitative study was conducted to describe motivations behind individuals’ decisions to participate – or not to participate – in the study.
METHODS
In July and August 2015, focus group discussions and semi-structured individual interviews were conducted in Conakry, Guinea. Individuals were eligible for the qualitative study if they met the inclusion criteria of the immunogenicity and safety study irrespective of their participation. Surveys were also conducted among several institution and department heads of staff included in the study as well as vaccine trial staff members. Discussion and interview transcripts were analyzed using content thematic analysis.
RESULTS
Interviews and focus groups were conducted among 110 persons, of whom about two-thirds (67%) participated in the vaccine trial. There was at least one group interview conducted at each participating trial site, along with numerous formal and informal interviews and conversations through the enrollment period. Participants were often motivated by a desire to save and protect themselves and others, contribute to scientific progress, or lead by example. Non-participants expressed concerns regarding the risk and costs of participation, particularly the fear of unknown side effects following vaccination, and distrust or fear of stigmatization.
CONCLUSIONS
Despite the unique nature of the 2014–2015 Ebola outbreak, front-line workers employed much of the same logic when choosing to participate as in other clinical trials in similar settings. Special consideration should be given to addressing perceived inequity, misunderstanding, and mistrust among the target populations in future trials.
CLINICAL TRIAL REGISTRY NUMBER
This trial is registered with the Pan African Clinical Trials Registry, number
PACTR201503001057193.
Alongside the clinical aspects of the immunogenicity and safety trial of an Ebola vaccine deployed among front-line workers, a qualitative study was conducted to describe motivations behind individuals’ decisions to participate – or not to participate – in the study.
METHODS
In July and August 2015, focus group discussions and semi-structured individual interviews were conducted in Conakry, Guinea. Individuals were eligible for the qualitative study if they met the inclusion criteria of the immunogenicity and safety study irrespective of their participation. Surveys were also conducted among several institution and department heads of staff included in the study as well as vaccine trial staff members. Discussion and interview transcripts were analyzed using content thematic analysis.
RESULTS
Interviews and focus groups were conducted among 110 persons, of whom about two-thirds (67%) participated in the vaccine trial. There was at least one group interview conducted at each participating trial site, along with numerous formal and informal interviews and conversations through the enrollment period. Participants were often motivated by a desire to save and protect themselves and others, contribute to scientific progress, or lead by example. Non-participants expressed concerns regarding the risk and costs of participation, particularly the fear of unknown side effects following vaccination, and distrust or fear of stigmatization.
CONCLUSIONS
Despite the unique nature of the 2014–2015 Ebola outbreak, front-line workers employed much of the same logic when choosing to participate as in other clinical trials in similar settings. Special consideration should be given to addressing perceived inequity, misunderstanding, and mistrust among the target populations in future trials.
CLINICAL TRIAL REGISTRY NUMBER
This trial is registered with the Pan African Clinical Trials Registry, number
PACTR201503001057193.
Journal Article > ResearchFull Text
Vaccine. 2019 November 15; Volume 37 (Issue 48); 7165-7170.; DOI:10.1016/j.vaccine.2019.09.094
Grantz KH, Claudot P, Kambala M, Kouyate M, Soumah A, et al.
Vaccine. 2019 November 15; Volume 37 (Issue 48); 7165-7170.; DOI:10.1016/j.vaccine.2019.09.094
BACKGROUND
Alongside the clinical aspects of the immunogenicity and safety trial of an Ebola vaccine deployed among front-line workers, a qualitative study was conducted to describe motivations behind individuals’ decisions to participate – or not to participate – in the study.
METHODS
In July and August 2015, focus group discussions and semi-structured individual interviews were conducted in Conakry, Guinea. Individuals were eligible for the qualitative study if they met the inclusion criteria of the immunogenicity and safety study irrespective of their participation. Surveys were also conducted among several institution and department heads of staff included in the study as well as vaccine trial staff members. Discussion and interview transcripts were analyzed using content thematic analysis.
RESULTS
Interviews and focus groups were conducted among 110 persons, of whom about two-thirds (67%) participated in the vaccine trial. There was at least one group interview conducted at each participating trial site, along with numerous formal and informal interviews and conversations through the enrollment period. Participants were often motivated by a desire to save and protect themselves and others, contribute to scientific progress, or lead by example. Non-participants expressed concerns regarding the risk and costs of participation, particularly the fear of unknown side effects following vaccination, and distrust or fear of stigmatization.
CONCLUSIONS
Despite the unique nature of the 2014–2015 Ebola outbreak, front-line workers employed much of the same logic when choosing to participate as in other clinical trials in similar settings. Special consideration should be given to addressing perceived inequity, misunderstanding, and mistrust among the target populations in future trials.
Alongside the clinical aspects of the immunogenicity and safety trial of an Ebola vaccine deployed among front-line workers, a qualitative study was conducted to describe motivations behind individuals’ decisions to participate – or not to participate – in the study.
METHODS
In July and August 2015, focus group discussions and semi-structured individual interviews were conducted in Conakry, Guinea. Individuals were eligible for the qualitative study if they met the inclusion criteria of the immunogenicity and safety study irrespective of their participation. Surveys were also conducted among several institution and department heads of staff included in the study as well as vaccine trial staff members. Discussion and interview transcripts were analyzed using content thematic analysis.
RESULTS
Interviews and focus groups were conducted among 110 persons, of whom about two-thirds (67%) participated in the vaccine trial. There was at least one group interview conducted at each participating trial site, along with numerous formal and informal interviews and conversations through the enrollment period. Participants were often motivated by a desire to save and protect themselves and others, contribute to scientific progress, or lead by example. Non-participants expressed concerns regarding the risk and costs of participation, particularly the fear of unknown side effects following vaccination, and distrust or fear of stigmatization.
CONCLUSIONS
Despite the unique nature of the 2014–2015 Ebola outbreak, front-line workers employed much of the same logic when choosing to participate as in other clinical trials in similar settings. Special consideration should be given to addressing perceived inequity, misunderstanding, and mistrust among the target populations in future trials.
Journal Article > ResearchFull Text
Lancet. 2017 February 1; Volume 389 (Issue 10068); 505-518.; DOI:10.1016/S0140-6736(16)32621-6
Henao-Restrepo AM, Camacho A, Longini I, Watson CH, Edmunds WJ, et al.
Lancet. 2017 February 1; Volume 389 (Issue 10068); 505-518.; DOI:10.1016/S0140-6736(16)32621-6
BACKGROUND
rVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa.
METHODS
We did an open-label, cluster-randomised ring vaccination trial (Ebola ça Suffit!) in the communities of Conakry and eight surrounding prefectures in the Basse-Guinée region of Guinea, and in Tomkolili and Bombali in Sierra Leone. We assessed the efficacy of a single intramuscular dose of rVSV-ZEBOV (2×107 plaque-forming units administered in the deltoid muscle) in the prevention of laboratory confirmed Ebola virus disease. After confirmation of a case of Ebola virus disease, we definitively enumerated on a list a ring (cluster) of all their contacts and contacts of contacts including named contacts and contacts of contacts who were absent at the time of the trial team visit. The list was archived, then we randomly assigned clusters (1:1) to either immediate vaccination or delayed vaccination (21 days later) of all eligible individuals (eg, those aged ≥18 years and not pregnant, breastfeeding, or severely ill). An independent statistician generated the assignment sequence using block randomisation with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 individuals vs >20 individuals). Ebola response teams and laboratory workers were unaware of assignments. After a recommendation by an independent data and safety monitoring board, randomisation was stopped and immediate vaccination was also offered to children aged 6–17 years and all identified rings. The prespecified primary outcome was a laboratory confirmed case of Ebola virus disease with onset 10 days or more from randomisation. The primary analysis compared the incidence of Ebola virus disease in eligible and vaccinated individuals assigned to immediate vaccination versus eligible contacts and contacts of contacts assigned to delayed vaccination. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193.
FINDINGS
In the randomised part of the trial we identified 4539 contacts and contacts of contacts in 51 clusters randomly assigned to immediate vaccination (of whom 3232 were eligible, 2151 consented, and 2119 were immediately vaccinated) and 4557 contacts and contacts of contacts in 47 clusters randomly assigned to delayed vaccination (of whom 3096 were eligible, 2539 consented, and 2041 were vaccinated 21 days after randomisation). No cases of Ebola virus disease occurred 10 days or more after randomisation among randomly assigned contacts and contacts of contacts vaccinated in immediate clusters versus 16 cases (7 clusters affected) among all eligible individuals in delayed clusters. Vaccine efficacy was 100% (95% CI 68·9–100·0, p=0·0045), and the calculated intraclass correlation coefficient was 0·035. Additionally, we defined 19 non-randomised clusters in which we enumerated 2745 contacts and contacts of contacts, 2006 of whom were eligible and 1677 were immediately vaccinated, including 194 children. The evidence from all 117 clusters showed that no cases of Ebola virus disease occurred 10 days or more after randomisation among all immediately vaccinated contacts and contacts of contacts versus 23 cases (11 clusters affected) among all eligible contacts and contacts of contacts in delayed plus all eligible contacts and contacts of contacts never vaccinated in immediate clusters. The estimated vaccine efficacy here was 100% (95% CI 79·3–100·0, p=0·0033). 52% of contacts and contacts of contacts assigned to immediate vaccination and in non-randomised clusters received the vaccine immediately; vaccination protected both vaccinated and unvaccinated people in those clusters. 5837 individuals in total received the vaccine (5643 adults and 194 children), and all vaccinees were followed up for 84 days. 3149 (53·9%) of 5837 individuals reported at least one adverse event in the 14 days after vaccination; these were typically mild (87·5% of all 7211 adverse events). Headache (1832 [25·4%]), fatigue (1361 [18·9%]), and muscle pain (942 [13·1%]) were the most commonly reported adverse events in this period across all age groups. 80 serious adverse events were identified, of which two were judged to be related to vaccination (one febrile reaction and one anaphylaxis) and one possibly related (influenza-like illness); all three recovered without sequelae.
INTERPRETATION
The results add weight to the interim assessment that rVSV-ZEBOV offers substantial protection against Ebola virus disease, with no cases among vaccinated individuals from day 10 after vaccination in both randomised and non-randomised clusters.
rVSV-ZEBOV is a recombinant, replication competent vesicular stomatitis virus-based candidate vaccine expressing a surface glycoprotein of Zaire Ebolavirus. We tested the effect of rVSV-ZEBOV in preventing Ebola virus disease in contacts and contacts of contacts of recently confirmed cases in Guinea, west Africa.
METHODS
We did an open-label, cluster-randomised ring vaccination trial (Ebola ça Suffit!) in the communities of Conakry and eight surrounding prefectures in the Basse-Guinée region of Guinea, and in Tomkolili and Bombali in Sierra Leone. We assessed the efficacy of a single intramuscular dose of rVSV-ZEBOV (2×107 plaque-forming units administered in the deltoid muscle) in the prevention of laboratory confirmed Ebola virus disease. After confirmation of a case of Ebola virus disease, we definitively enumerated on a list a ring (cluster) of all their contacts and contacts of contacts including named contacts and contacts of contacts who were absent at the time of the trial team visit. The list was archived, then we randomly assigned clusters (1:1) to either immediate vaccination or delayed vaccination (21 days later) of all eligible individuals (eg, those aged ≥18 years and not pregnant, breastfeeding, or severely ill). An independent statistician generated the assignment sequence using block randomisation with randomly varying blocks, stratified by location (urban vs rural) and size of rings (≤20 individuals vs >20 individuals). Ebola response teams and laboratory workers were unaware of assignments. After a recommendation by an independent data and safety monitoring board, randomisation was stopped and immediate vaccination was also offered to children aged 6–17 years and all identified rings. The prespecified primary outcome was a laboratory confirmed case of Ebola virus disease with onset 10 days or more from randomisation. The primary analysis compared the incidence of Ebola virus disease in eligible and vaccinated individuals assigned to immediate vaccination versus eligible contacts and contacts of contacts assigned to delayed vaccination. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201503001057193.
FINDINGS
In the randomised part of the trial we identified 4539 contacts and contacts of contacts in 51 clusters randomly assigned to immediate vaccination (of whom 3232 were eligible, 2151 consented, and 2119 were immediately vaccinated) and 4557 contacts and contacts of contacts in 47 clusters randomly assigned to delayed vaccination (of whom 3096 were eligible, 2539 consented, and 2041 were vaccinated 21 days after randomisation). No cases of Ebola virus disease occurred 10 days or more after randomisation among randomly assigned contacts and contacts of contacts vaccinated in immediate clusters versus 16 cases (7 clusters affected) among all eligible individuals in delayed clusters. Vaccine efficacy was 100% (95% CI 68·9–100·0, p=0·0045), and the calculated intraclass correlation coefficient was 0·035. Additionally, we defined 19 non-randomised clusters in which we enumerated 2745 contacts and contacts of contacts, 2006 of whom were eligible and 1677 were immediately vaccinated, including 194 children. The evidence from all 117 clusters showed that no cases of Ebola virus disease occurred 10 days or more after randomisation among all immediately vaccinated contacts and contacts of contacts versus 23 cases (11 clusters affected) among all eligible contacts and contacts of contacts in delayed plus all eligible contacts and contacts of contacts never vaccinated in immediate clusters. The estimated vaccine efficacy here was 100% (95% CI 79·3–100·0, p=0·0033). 52% of contacts and contacts of contacts assigned to immediate vaccination and in non-randomised clusters received the vaccine immediately; vaccination protected both vaccinated and unvaccinated people in those clusters. 5837 individuals in total received the vaccine (5643 adults and 194 children), and all vaccinees were followed up for 84 days. 3149 (53·9%) of 5837 individuals reported at least one adverse event in the 14 days after vaccination; these were typically mild (87·5% of all 7211 adverse events). Headache (1832 [25·4%]), fatigue (1361 [18·9%]), and muscle pain (942 [13·1%]) were the most commonly reported adverse events in this period across all age groups. 80 serious adverse events were identified, of which two were judged to be related to vaccination (one febrile reaction and one anaphylaxis) and one possibly related (influenza-like illness); all three recovered without sequelae.
INTERPRETATION
The results add weight to the interim assessment that rVSV-ZEBOV offers substantial protection against Ebola virus disease, with no cases among vaccinated individuals from day 10 after vaccination in both randomised and non-randomised clusters.
Journal Article > ResearchFull Text
Vaccine. 2018 September 25; Volume 37 (Issue 48); DOI:10.1016/j.vaccine.2018.09.009
Juan-Giner A, Tchaton M, Jemmy J-P, Soumah A, Boum Y II, et al.
Vaccine. 2018 September 25; Volume 37 (Issue 48); DOI:10.1016/j.vaccine.2018.09.009
As part of the ring vaccination trial in Guinea, Front Line Workers were invited to participate in a sub-study to provide additional information on the immunogenicity and safety of rVSVΔG/ZEBOV-GP. Here we summarize the information on the safety follow-up.