Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in infants: a phase 2, randomised, double-blind, active-controlled trial in Guinea and Sierra Leone.

Animals Humans Infant Ebola Vaccines / adverse effects Hemorrhagic Fever, Ebola / prevention & control Ebolavirus Sierra Leone Guinea Antibodies, Viral Double-Blind Method Glycoproteins Fever

Journal

The Lancet. Global health

ISSN: 2214-109X

Titre abrégé: Lancet Glob Health

Pays: England

ID NLM: 101613665

Informations de publication

Date de publication:
11 2023

Historique:

received: 21 04 2023

revised: 11 08 2023

accepted: 17 08 2023

medline: 23 10 2023

pubmed: 20 10 2023

entrez: 20 10 2023

Statut: ppublish

Résumé

This study assessed the safety and immunogenicity of the Ad26.ZEBOV and MVA-BN-Filo Ebola virus (EBOV) vaccine regimen in infants aged 4-11 months in Guinea and Sierra Leone. In this phase 2, randomised, double-blind, active-controlled trial, we randomly assigned healthy infants (1:1 in a sentinel cohort, 5:2 for the remaining infants via an interactive web response system) to receive Ad26.ZEBOV followed by MVA-BN-Filo (Ebola vaccine group) or two doses of meningococcal quadrivalent conjugate vaccine (control group) administered 56 days apart. Infants were recruited at two sites in west Africa: Conakry, Guinea, and Kambia, Sierra Leone. All infants received the meningococcal vaccine 8 months after being randomly assigned. The primary objective was safety. The secondary objective was immunogenicity, measured as EBOV glycoprotein-binding antibody concentration 21 days post-dose 2, using the Filovirus Animal Non-Clinical Group ELISA. This study is registered with ClinicalTrials.gov (NCT03929757) and the Pan African Clinical Trials Registry (PACTR201905827924069). From Aug 20 to Nov 29, 2019, 142 infants were screened and 108 were randomly assigned (Ebola vaccine n=75; control n=33). The most common solicited local adverse event was injection-site pain (Ebola vaccine 15 [20%] of 75; control four [12%] of 33). The most common solicited systemic adverse events with the Ebola vaccine were irritability (26 [35%] of 75), decreased appetite (18 [24%] of 75), pyrexia (16 [21%] of 75), and decreased activity (15 [20%] of 75). In the control group, ten (30%) of 33 had irritability, seven (21%) of 33 had decreased appetite, three (9%) of 33 had pyrexia, and five (15%) of 33 had decreased activity. The frequency of unsolicited adverse events was 83% (62 of 75 infants) in the Ebola vaccine group and 85% (28 of 33 infants) in the control group. No serious adverse events were vaccine-related. In the Ebola vaccine group, EBOV glycoprotein-binding antibody geometric mean concentrations (GMCs) at 21 days post-dose 2 were 27 700 ELISA units (EU)/mL (95% CI 20 477-37 470) in infants aged 4-8 months and 20 481 EU/mL (15 325-27 372) in infants aged 9-11 months. The responder rate was 100% (74 of 74 responded). In the control group, GMCs for both age groups were less than the lower limit of quantification and the responder rate was 3% (one of 33 responded). Ad26.ZEBOV and MVA-BN-Filo was well tolerated and induced strong humoral responses in infants younger than 1 year. There were no safety concerns related to vaccination. Janssen Vaccines & Prevention and Innovative Medicines Initiative 2 Joint Undertaking. For the French translation of the abstract see Supplementary Materials section.

Sections du résumé

BACKGROUND

This study assessed the safety and immunogenicity of the Ad26.ZEBOV and MVA-BN-Filo Ebola virus (EBOV) vaccine regimen in infants aged 4-11 months in Guinea and Sierra Leone.

METHODS

In this phase 2, randomised, double-blind, active-controlled trial, we randomly assigned healthy infants (1:1 in a sentinel cohort, 5:2 for the remaining infants via an interactive web response system) to receive Ad26.ZEBOV followed by MVA-BN-Filo (Ebola vaccine group) or two doses of meningococcal quadrivalent conjugate vaccine (control group) administered 56 days apart. Infants were recruited at two sites in west Africa: Conakry, Guinea, and Kambia, Sierra Leone. All infants received the meningococcal vaccine 8 months after being randomly assigned. The primary objective was safety. The secondary objective was immunogenicity, measured as EBOV glycoprotein-binding antibody concentration 21 days post-dose 2, using the Filovirus Animal Non-Clinical Group ELISA. This study is registered with ClinicalTrials.gov (NCT03929757) and the Pan African Clinical Trials Registry (PACTR201905827924069).

FINDINGS

From Aug 20 to Nov 29, 2019, 142 infants were screened and 108 were randomly assigned (Ebola vaccine n=75; control n=33). The most common solicited local adverse event was injection-site pain (Ebola vaccine 15 [20%] of 75; control four [12%] of 33). The most common solicited systemic adverse events with the Ebola vaccine were irritability (26 [35%] of 75), decreased appetite (18 [24%] of 75), pyrexia (16 [21%] of 75), and decreased activity (15 [20%] of 75). In the control group, ten (30%) of 33 had irritability, seven (21%) of 33 had decreased appetite, three (9%) of 33 had pyrexia, and five (15%) of 33 had decreased activity. The frequency of unsolicited adverse events was 83% (62 of 75 infants) in the Ebola vaccine group and 85% (28 of 33 infants) in the control group. No serious adverse events were vaccine-related. In the Ebola vaccine group, EBOV glycoprotein-binding antibody geometric mean concentrations (GMCs) at 21 days post-dose 2 were 27 700 ELISA units (EU)/mL (95% CI 20 477-37 470) in infants aged 4-8 months and 20 481 EU/mL (15 325-27 372) in infants aged 9-11 months. The responder rate was 100% (74 of 74 responded). In the control group, GMCs for both age groups were less than the lower limit of quantification and the responder rate was 3% (one of 33 responded).

INTERPRETATION

Ad26.ZEBOV and MVA-BN-Filo was well tolerated and induced strong humoral responses in infants younger than 1 year. There were no safety concerns related to vaccination.

FUNDING

Janssen Vaccines & Prevention and Innovative Medicines Initiative 2 Joint Undertaking.

TRANSLATION

For the French translation of the abstract see Supplementary Materials section.

Identifiants

DOI: 10.1016/S2214-109X(23)00410-2 PMID: 37858585

pubmed: 37858585

pii: S2214-109X(23)00410-2

doi: 10.1016/S2214-109X(23)00410-2

pii:

doi:

Substances chimiques

Ebola Vaccines 0

smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic TU8J357395

Antibodies, Viral 0

Glycoproteins 0

Banques de données

ClinicalTrials.gov

['NCT03929757']

PACTR

['PACTR201905827924069']

Types de publication

Randomized Controlled Trial Clinical Trial, Phase II Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

e1743-e1752

Subventions

Organisme : Medical Research Council

ID : MR/S03286X/1

Pays : United Kingdom

Investigateurs

T Mooney (T)

L Conteh (L)

M S Bangura (MS)

M A Bangura (MA)

H Jalloh (H)

I Kamara (I)

M Kamara (M)

S Koroma (S)

M Sesay (M)

M T Sesay (MT)

A T Deen (AT)

A Kamara (A)

E L Kamara (EL)

Slm Kamara (S)

A H Koroma (AH)

I S Mansaray (IS)

M J Massaquoi (MJ)

A Nabie (A)

D Kowuor (D)

Y Njie (Y)

L Odeny (L)

M Sheku (M)

A B Jalloh (AB)

A Sow (A)

E Swaray (E)

F Mansaray (F)

T Sessie (T)

J-Hc Sunders (JH)

Si-S Turay (SS)

J Weekes (J)

M Pessima (M)

A Wurie (A)

M Conteh (M)

M I Jalloh (MI)

Pbd Kamara (P)

D P Kanneh (DP)

M Kanneh (M)

I Komeh (I)

M Koroma (M)

M Kuyateh (M)

F F Mansaray (FF)

B Leigh (B)

D Watson-Jones (D)

M Samai (M)

G F Deen (GF)

T Sesay (T)

P Piot (P)

B Greenwood (B)

S Lees (S)

H Larson (H)

M Afolabi (M)

D Ishola (D)

F Baiden (F)

F Faye (F)

D Tindanbil (D)

M M Kamara (MM)

I B Swaray (IB)

A Bangura (A)

A B Kamara (AB)

F E Morovia (FE)

J A Kallon (JA)

M Murray (M)

F Sesay (F)

F Suma (F)

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E M Choi (EM)

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J Foster (J)

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Commentaires et corrections

Type : CommentIn

Type : ErratumIn

Informations de copyright

Déclaration de conflit d'intérêts

Declaration of interests Janssen Vaccines & Prevention was the vaccine manufacturer and donated the vaccine for this study. BK, WvD, AG, DA, CM, ML, KL, CR, and MD were full-time employees of Janssen Pharmaceuticals at the time of the study and hold stock or stock options in Janssen Pharmaceuticals. All other authors declare funding from the Innovative Medicines Initiative 2 Joint Undertaking.