Safety and immunogenicity of an Ad26.ZEBOV booster vaccine in Human Immunodeficiency Virus positive (HIV+) adults previously vaccinated with the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen against Ebola: A single-arm, open-label Phase II clinical trial in Kenya and Uganda.
Ad26.ZEBOV
Booster
Clinical trial
Ebola vaccine
HIV
MVA-BN-Filo
Journal
Vaccine
ISSN: 1873-2518
Titre abrégé: Vaccine
Pays: Netherlands
ID NLM: 8406899
Informations de publication
Date de publication:
07 Dec 2023
07 Dec 2023
Historique:
received:
23
05
2023
revised:
17
08
2023
accepted:
20
10
2023
medline:
4
12
2023
pubmed:
20
11
2023
entrez:
19
11
2023
Statut:
ppublish
Résumé
People living with HIV constitute an important part of the population in regions at risk of Ebola virus disease outbreaks. The two-dose Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen induces strong immune responses in HIV-positive (HIV+) adults but the durability of this response is unknown. It is also unclear whether this regimen can establish immune memory to enable an anamnestic response upon re-exposure to antigen. This paper describes an open-label, phase 2 trial, conducted in Kenya and Uganda, of Ad26.ZEBOV booster vaccination in HIV+ participants who had previously received the Ad26.ZEBOV, MVA-BN-Filo primary regimen. HIV+ adults with well-controlled infection and on highly active antiretroviral therapy were enrolled, vaccinated with booster, and followed for 28 days. The primary objectives were to assess Ad26.ZEBOV booster safety and antibody responses against the Ebola virus glycoprotein using the Filovirus Animal Non-Clinical Group ELISA. The Ad26.ZEBOV booster was well-tolerated in HIV+ adults with mostly mild to moderate symptoms. No major safety concerns or serious adverse events were reported. Four and a half years after the primary regimen, 24/26 (92 %) participants were still classified as responders, with a pre-booster antibody geometric mean concentration (GMC) of 726 ELISA units (EU)/mL (95 %CI 447-1179). Seven days after the booster, the GMC increased 54-fold to 38,965 EU/mL (95 %CI 23532-64522). Twenty-one days after the booster, the GMC increased 176-fold to 127,959 EU/mL (95 %CI 93872-174422). The responder rate at both post-booster time points was 100 %. The Ad26.ZEBOV booster is safe and highly immunogenic in HIV+ adults with well-controlled infection. The Ad26.ZEBOV, MVA-BN-Filo regimen can generate long-term immune memory persisting for at least 4·5 years, resulting in a robust anamnestic response. Pan African Clinical Trial Registry (PACTR202102747294430). gov (NCT05064956).
Sections du résumé
BACKGROUND
BACKGROUND
People living with HIV constitute an important part of the population in regions at risk of Ebola virus disease outbreaks. The two-dose Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen induces strong immune responses in HIV-positive (HIV+) adults but the durability of this response is unknown. It is also unclear whether this regimen can establish immune memory to enable an anamnestic response upon re-exposure to antigen.
METHODS
METHODS
This paper describes an open-label, phase 2 trial, conducted in Kenya and Uganda, of Ad26.ZEBOV booster vaccination in HIV+ participants who had previously received the Ad26.ZEBOV, MVA-BN-Filo primary regimen. HIV+ adults with well-controlled infection and on highly active antiretroviral therapy were enrolled, vaccinated with booster, and followed for 28 days. The primary objectives were to assess Ad26.ZEBOV booster safety and antibody responses against the Ebola virus glycoprotein using the Filovirus Animal Non-Clinical Group ELISA.
RESULTS
RESULTS
The Ad26.ZEBOV booster was well-tolerated in HIV+ adults with mostly mild to moderate symptoms. No major safety concerns or serious adverse events were reported. Four and a half years after the primary regimen, 24/26 (92 %) participants were still classified as responders, with a pre-booster antibody geometric mean concentration (GMC) of 726 ELISA units (EU)/mL (95 %CI 447-1179). Seven days after the booster, the GMC increased 54-fold to 38,965 EU/mL (95 %CI 23532-64522). Twenty-one days after the booster, the GMC increased 176-fold to 127,959 EU/mL (95 %CI 93872-174422). The responder rate at both post-booster time points was 100 %.
CONCLUSIONS
CONCLUSIONS
The Ad26.ZEBOV booster is safe and highly immunogenic in HIV+ adults with well-controlled infection. The Ad26.ZEBOV, MVA-BN-Filo regimen can generate long-term immune memory persisting for at least 4·5 years, resulting in a robust anamnestic response.
TRIAL REGISTRATION
BACKGROUND
Pan African Clinical Trial Registry (PACTR202102747294430).
CLINICALTRIALS
RESULTS
gov (NCT05064956).
Identifiants
pubmed: 37981473
pii: S0264-410X(23)01257-4
doi: 10.1016/j.vaccine.2023.10.055
pii:
doi:
Substances chimiques
Antibodies, Viral
0
Ebola Vaccines
0
smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
TU8J357395
Banques de données
ClinicalTrials.gov
['NCT05064956']
Types de publication
Clinical Trial, Phase II
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7573-7580Subventions
Organisme : Medical Research Council
ID : MC_UU_00027/5
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K019708/1
Pays : United Kingdom
Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Janssen Vaccines & Prevention B.V. was the vaccine manufacturer and donated the vaccine for this study. BKe, AG, CM, KL, and CR were full-time employees of Janssen, Pharmaceutical Companies of Johnson & Johnson at the time of the study. AG, CM, KL, and CR, declared ownership of shares in Janssen, Pharmaceutical Companies of Johnson & Johnson. All other authors declare funding from the Innovative Medicines Initiative 2 Joint Undertaking. GAM reports having received travel grant from the vaccine manufacturer to attend scientific meetings and present, after the study has completed.