Live-attenuated Mycobacterium tuberculosis vaccine MTBVAC versus BCG in adults and neonates: a randomised controlled, double-blind dose-escalation trial.

Adolescent Adult BCG Vaccine / administration & dosage Dose-Response Relationship, Drug Double-Blind Method Drug Administration Routes Female Humans Male Middle Aged Mycobacterium tuberculosis / immunology South Africa Tuberculosis / immunology Tuberculosis Vaccines / administration & dosage Vaccines, Attenuated / administration & dosage Young Adult

Journal

The Lancet. Respiratory medicine

ISSN: 2213-2619

Titre abrégé: Lancet Respir Med

Pays: England

ID NLM: 101605555

Informations de publication

Date de publication:
09 2019

Historique:

received: 03 03 2019

revised: 26 06 2019

accepted: 26 06 2019

pubmed: 17 8 2019

medline: 4 7 2020

entrez: 17 8 2019

Statut: ppublish

Résumé

Infants are a key target population for new tuberculosis vaccines. We assessed the safety and immunogenicity of the live-attenuated Mycobacterium tuberculosis vaccine candidate MTBVAC in adults and infants in a region where transmission of tuberculosis is very high. We did a randomised, double-blind, BCG-controlled, dose-escalation trial at the South African Tuberculosis Vaccine Initiative site near Cape Town, South Africa. Healthy adult community volunteers who were aged 18-50 years, had received BCG vaccination as infants, were HIV negative, had negative interferon-γ release assay (IGRA) results, and had no personal history of tuberculosis or current household contact with someone with tuberculosis were enrolled in a safety cohort. Infants born to HIV-negative women with no personal history of tuberculosis or current household contact with a person with tuberculosis and who were 96 h old or younger, generally healthy, and had not yet received routine BCG vaccination were enrolled in a separate infant cohort. Eligible adults were randomly assigned (1:1) to receive either BCG Vaccine SSI (5 × 10 Between Sept 29, 2015, and Nov 16, 2015, 62 adults were screened and 18 were enrolled and randomly assigned, nine each to the BCG and MTBVAC groups. Between Feb 12, 2016, and Sept 21, 2016, 36 infants were randomly assigned-eight to the BCG group, nine to the 2·5 × 10 MTBVAC had acceptable reactogenicity, and induced a durable CD4 cell response in infants. The evidence of immunogenicity supports progression of MTBVAC into larger safety and efficacy trials, but also confounds interpretation of tests for M tuberculosis infection, highlighting the need for stringent endpoint definition. Norwegian Agency for Development Cooperation, TuBerculosis Vaccine Initiative, UK Department for International Development, and Biofabri.

Sections du résumé

BACKGROUND

METHODS

We did a randomised, double-blind, BCG-controlled, dose-escalation trial at the South African Tuberculosis Vaccine Initiative site near Cape Town, South Africa. Healthy adult community volunteers who were aged 18-50 years, had received BCG vaccination as infants, were HIV negative, had negative interferon-γ release assay (IGRA) results, and had no personal history of tuberculosis or current household contact with someone with tuberculosis were enrolled in a safety cohort. Infants born to HIV-negative women with no personal history of tuberculosis or current household contact with a person with tuberculosis and who were 96 h old or younger, generally healthy, and had not yet received routine BCG vaccination were enrolled in a separate infant cohort. Eligible adults were randomly assigned (1:1) to receive either BCG Vaccine SSI (5 × 10

FINDINGS

Between Sept 29, 2015, and Nov 16, 2015, 62 adults were screened and 18 were enrolled and randomly assigned, nine each to the BCG and MTBVAC groups. Between Feb 12, 2016, and Sept 21, 2016, 36 infants were randomly assigned-eight to the BCG group, nine to the 2·5 × 10

INTERPRETATION

MTBVAC had acceptable reactogenicity, and induced a durable CD4 cell response in infants. The evidence of immunogenicity supports progression of MTBVAC into larger safety and efficacy trials, but also confounds interpretation of tests for M tuberculosis infection, highlighting the need for stringent endpoint definition.

FUNDING

Norwegian Agency for Development Cooperation, TuBerculosis Vaccine Initiative, UK Department for International Development, and Biofabri.

Identifiants

DOI: 10.1016/S2213-2600(19)30251-6 PMID: 31416768

pubmed: 31416768

pii: S2213-2600(19)30251-6

doi: 10.1016/S2213-2600(19)30251-6

pii:

doi:

Substances chimiques

BCG Vaccine 0

MTBVAC vaccine 0

Tuberculosis Vaccines 0

Vaccines, Attenuated 0

Banques de données

ClinicalTrials.gov

['NCT02729571']

Types de publication

Comparative Study Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

757-770

Investigateurs

Hadn Africa (H)

Denis Arendsen (D)

Natasja Botes (N)

Yolundi Cloete (Y)

Marwou De Kock (M)

Margaret Erasmus (M)

Lungisa Jack (L)

Fazlin Kafaar (F)

Xoliswa Kalepu (X)

Nondumiso Gloria Khomba (NG)

Sandra Kruger (S)

Thelma Leopeng (T)

Lebohang Makhethe (L)

Angelique Mouton (A)

Humphrey Mulenga (H)

Munyaradzi Musvosvi (M)

Julia Noble (J)

Fajwa Opperman (F)

Tim Reid (T)

Susan Rossouw (S)

Constance Schreuder (C)

Erica Smit (E)

Marcia Steyn (M)

Petrus Tyambethu (P)

Elma Van Rooyen (E)

Ashley Veldsman (A)

Commentaires et corrections

Type : CommentIn