Listeria-vectored multi-antigenic tuberculosis vaccine protects C57BL/6 and BALB/c mice and guinea pigs against Mycobacterium tuberculosis challenge

© 2022. The Author(s)..

Mycobacterium tuberculosis (Mtb) infects one-third of the world's population and is a leading cause of death from a single infectious agent. New TB vaccines are urgently needed to augment immunity conferred by the current modestly protective BCG vaccine. We have developed live attenuated recombinant Listeria monocytogenes (rLm)-vectored TB vaccines expressing five [Mpt64/23.5-EsxH/TB10.4-EsxA/ESAT6-EsxB/CFP10-Ag85B/r30] (rLmMtb5Ag) or nine (additionally EsxN-PPE68-EspA-TB8.4) immunoprotective Mtb antigens (rLmMtb9Ag) and evaluated them for safety, immunogenicity and efficacy as standalone vaccines in two mouse models and an outbred guinea pig model. In immunogenicity studies, rLmMtb5Ag administered subcutaneously induces significantly enhanced antigen-specific CD4+ and CD8+ T-cell responses in C57BL/6 and BALB/c mice, and rLmMtb9Ag induces antigen-specific CD4+ and CD8+ T-cell proliferation in guinea pigs. In efficacy studies, both rLmMtb5Ag and rLmMtb9Ag are safe and protect C57BL/6 and BALB/c mice and guinea pigs against aerosol challenge with highly virulent Mtb. Hence, multi-antigenic rLm vaccines hold promise as new vaccines against TB.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:5

Enthalten in:

Communications biology - 5(2022), 1 vom: 20. Dez., Seite 1388

Sprache:

Englisch

Beteiligte Personen:

Jia, Qingmei [VerfasserIn]
Masleša-Galić, Saša [VerfasserIn]
Nava, Susana [VerfasserIn]
Horwitz, Marcus A [VerfasserIn]

Links:

Volltext

Themen:

82115-62-6
Antigens, Bacterial
Interferon-gamma
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Tuberculosis Vaccines

Anmerkungen:

Date Completed 22.12.2022

Date Revised 07.07.2023

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s42003-022-04345-1

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM350511578