Scientific article
OA Policy
English

Replication-Deficient Lymphocytic Choriomeningitis Virus-Vectored Vaccine Candidate for the Induction of T Cell Immunity against Mycobacterium tuberculosis

Published inInternational journal of molecular sciences, vol. 23, no. 5, 2700
Publication date2022-02-28
First online date2022-02-28
Abstract

Mycobacterium tuberculosis(Mtb) represents a major burden to global health, and refined vaccines are needed. Replication-deficient lymphocytic choriomeningitis virus (rLCMV)-based vaccine vectors against cytomegalovirus have proven safe for human use and elicited robust T cell responses in a large proportion of vaccine recipients. Here, we developed an rLCMV vaccine expressing theMtbantigens TB10.4 and Ag85B. In mice, rLCMV elicited high frequencies of polyfunctionalMtb-specific CD8 and CD4 T cell responses. CD8 but not CD4 T cells were efficiently boosted upon vector re-vaccination. High-frequency responses were also observed in neonatally vaccinated mice, and co-administration of rLCMV with Expanded Program of Immunization (EPI) vaccines did not result in substantial reciprocal interference. Importantly, rLCMV immunization significantly reduced the lungMtbburden upon aerosol challenge, resulting in improved lung ventilation. Protection was associated with increased CD8 T cell recruitment but reduced CD4 T cell infiltration uponMtbchallenge. When combining rLCMV with BCG vaccination in a heterologous prime-boost regimen, responses to the rLCMV-encodedMtbantigens were further augmented, but protection was not significantly different from rLCMV or BCG vaccination alone. This work suggests that rLCMV may show utility for neonatal and/or adult vaccination efforts against pulmonary tuberculosis.

Keywords
  • Bacille Calmette Guerin (BCG) heterologous prime-boost
  • Mycobacterium tuberculosis
  • T cell immunity
  • Lymphocytic choriomeningitis virus (LCMV)
  • Neonatal vaccination
  • Replication-deficient LCMV vector
  • Vaccine
  • Animals
  • Antigens, Bacterial
  • BCG Vaccine
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Lymphocytic choriomeningitis virus / genetics
  • Mice
  • Mycobacterium tuberculosis / genetics
Citation (ISO format)
BELNOUE, Elodie et al. Replication-Deficient Lymphocytic Choriomeningitis Virus-Vectored Vaccine Candidate for the Induction of T Cell Immunity against Mycobacterium tuberculosis. In: International journal of molecular sciences, 2022, vol. 23, n° 5, p. 2700. doi: 10.3390/ijms23052700
Main files (1)
Article (Published version)
Identifiers
Journal ISSN1422-0067
275views
189downloads

Technical informations

Creation26/01/2023 13:05:00
First validation26/01/2023 13:05:00
Update16/03/2023 10:31:25
Status update16/03/2023 10:31:24
Last indexation01/11/2024 04:03:24
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack