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

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...

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Autores principales: Belnoue, Elodie, Vogelzang, Alexis, Nieuwenhuizen, Natalie E., Krzyzaniak, Magdalena A., Darbre, Stephanie, Kreutzfeldt, Mario, Wagner, Ingrid, Merkler, Doron, Lambert, Paul-Henri, Kaufmann, Stefan H. E., Siegrist, Claire-Anne, Pinschewer, Daniel D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911050/
https://www.ncbi.nlm.nih.gov/pubmed/35269842
http://dx.doi.org/10.3390/ijms23052700
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author Belnoue, Elodie
Vogelzang, Alexis
Nieuwenhuizen, Natalie E.
Krzyzaniak, Magdalena A.
Darbre, Stephanie
Kreutzfeldt, Mario
Wagner, Ingrid
Merkler, Doron
Lambert, Paul-Henri
Kaufmann, Stefan H. E.
Siegrist, Claire-Anne
Pinschewer, Daniel D.
author_facet Belnoue, Elodie
Vogelzang, Alexis
Nieuwenhuizen, Natalie E.
Krzyzaniak, Magdalena A.
Darbre, Stephanie
Kreutzfeldt, Mario
Wagner, Ingrid
Merkler, Doron
Lambert, Paul-Henri
Kaufmann, Stefan H. E.
Siegrist, Claire-Anne
Pinschewer, Daniel D.
author_sort Belnoue, Elodie
collection PubMed
description 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 the Mtb antigens TB10.4 and Ag85B. In mice, rLCMV elicited high frequencies of polyfunctional Mtb-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 lung Mtb burden upon aerosol challenge, resulting in improved lung ventilation. Protection was associated with increased CD8 T cell recruitment but reduced CD4 T cell infiltration upon Mtb challenge. When combining rLCMV with BCG vaccination in a heterologous prime-boost regimen, responses to the rLCMV-encoded Mtb antigens 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.
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spelling pubmed-89110502022-03-11 Replication-Deficient Lymphocytic Choriomeningitis Virus-Vectored Vaccine Candidate for the Induction of T Cell Immunity against Mycobacterium tuberculosis Belnoue, Elodie Vogelzang, Alexis Nieuwenhuizen, Natalie E. Krzyzaniak, Magdalena A. Darbre, Stephanie Kreutzfeldt, Mario Wagner, Ingrid Merkler, Doron Lambert, Paul-Henri Kaufmann, Stefan H. E. Siegrist, Claire-Anne Pinschewer, Daniel D. Int J Mol Sci Article 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 the Mtb antigens TB10.4 and Ag85B. In mice, rLCMV elicited high frequencies of polyfunctional Mtb-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 lung Mtb burden upon aerosol challenge, resulting in improved lung ventilation. Protection was associated with increased CD8 T cell recruitment but reduced CD4 T cell infiltration upon Mtb challenge. When combining rLCMV with BCG vaccination in a heterologous prime-boost regimen, responses to the rLCMV-encoded Mtb antigens 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. MDPI 2022-02-28 /pmc/articles/PMC8911050/ /pubmed/35269842 http://dx.doi.org/10.3390/ijms23052700 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Belnoue, Elodie
Vogelzang, Alexis
Nieuwenhuizen, Natalie E.
Krzyzaniak, Magdalena A.
Darbre, Stephanie
Kreutzfeldt, Mario
Wagner, Ingrid
Merkler, Doron
Lambert, Paul-Henri
Kaufmann, Stefan H. E.
Siegrist, Claire-Anne
Pinschewer, Daniel D.
Replication-Deficient Lymphocytic Choriomeningitis Virus-Vectored Vaccine Candidate for the Induction of T Cell Immunity against Mycobacterium tuberculosis
title Replication-Deficient Lymphocytic Choriomeningitis Virus-Vectored Vaccine Candidate for the Induction of T Cell Immunity against Mycobacterium tuberculosis
title_full Replication-Deficient Lymphocytic Choriomeningitis Virus-Vectored Vaccine Candidate for the Induction of T Cell Immunity against Mycobacterium tuberculosis
title_fullStr Replication-Deficient Lymphocytic Choriomeningitis Virus-Vectored Vaccine Candidate for the Induction of T Cell Immunity against Mycobacterium tuberculosis
title_full_unstemmed Replication-Deficient Lymphocytic Choriomeningitis Virus-Vectored Vaccine Candidate for the Induction of T Cell Immunity against Mycobacterium tuberculosis
title_short Replication-Deficient Lymphocytic Choriomeningitis Virus-Vectored Vaccine Candidate for the Induction of T Cell Immunity against Mycobacterium tuberculosis
title_sort replication-deficient lymphocytic choriomeningitis virus-vectored vaccine candidate for the induction of t cell immunity against mycobacterium tuberculosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911050/
https://www.ncbi.nlm.nih.gov/pubmed/35269842
http://dx.doi.org/10.3390/ijms23052700
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