date: 2022-02-28T15:07:25Z
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pdf:docinfo:title: Replication-Deficient Lymphocytic Choriomeningitis Virus-Vectored Vaccine Candidate for the Induction of T Cell Immunity against Mycobacterium tuberculosis
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Keywords: Mycobacterium tuberculosis; vaccine; lymphocytic choriomeningitis virus (LCMV); T cell immunity; neonatal vaccination; replication-deficient LCMV vector; Bacille Calmette Guerin (BCG) heterologous prime-boost
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subject: 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.
dc:creator: Elodie Belnoue, Alexis Vogelzang, Natalie E. Nieuwenhuizen, Magdalena A. Krzyzaniak, Stephanie Darbre, Mario Kreutzfeldt, Ingrid Wagner, Doron Merkler, Paul-Henri Lambert, Stefan H. E. Kaufmann, Claire-Anne Siegrist and Daniel D. Pinschewer
dcterms:created: 2022-02-28T15:02:38Z
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title: Replication-Deficient Lymphocytic Choriomeningitis Virus-Vectored Vaccine Candidate for the Induction of T Cell Immunity against Mycobacterium tuberculosis
Last-Save-Date: 2022-02-28T15:07:25Z
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pdf:docinfo:keywords: Mycobacterium tuberculosis; vaccine; lymphocytic choriomeningitis virus (LCMV); T cell immunity; neonatal vaccination; replication-deficient LCMV vector; Bacille Calmette Guerin (BCG) heterologous prime-boost
pdf:docinfo:modified: 2022-02-28T15:07:25Z
meta:save-date: 2022-02-28T15:07:25Z
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dc:title: Replication-Deficient Lymphocytic Choriomeningitis Virus-Vectored Vaccine Candidate for the Induction of T Cell Immunity against Mycobacterium tuberculosis
modified: 2022-02-28T15:07:25Z
cp:subject: 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.
pdf:docinfo:subject: 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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pdf:docinfo:creator: Elodie Belnoue, Alexis Vogelzang, Natalie E. Nieuwenhuizen, Magdalena A. Krzyzaniak, Stephanie Darbre, Mario Kreutzfeldt, Ingrid Wagner, Doron Merkler, Paul-Henri Lambert, Stefan H. E. Kaufmann, Claire-Anne Siegrist and Daniel D. Pinschewer
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creator: Elodie Belnoue, Alexis Vogelzang, Natalie E. Nieuwenhuizen, Magdalena A. Krzyzaniak, Stephanie Darbre, Mario Kreutzfeldt, Ingrid Wagner, Doron Merkler, Paul-Henri Lambert, Stefan H. E. Kaufmann, Claire-Anne Siegrist and Daniel D. Pinschewer
meta:author: Elodie Belnoue, Alexis Vogelzang, Natalie E. Nieuwenhuizen, Magdalena A. Krzyzaniak, Stephanie Darbre, Mario Kreutzfeldt, Ingrid Wagner, Doron Merkler, Paul-Henri Lambert, Stefan H. E. Kaufmann, Claire-Anne Siegrist and Daniel D. Pinschewer
dc:subject: Mycobacterium tuberculosis; vaccine; lymphocytic choriomeningitis virus (LCMV); T cell immunity; neonatal vaccination; replication-deficient LCMV vector; Bacille Calmette Guerin (BCG) heterologous prime-boost
meta:creation-date: 2022-02-28T15:02:38Z
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meta:keyword: Mycobacterium tuberculosis; vaccine; lymphocytic choriomeningitis virus (LCMV); T cell immunity; neonatal vaccination; replication-deficient LCMV vector; Bacille Calmette Guerin (BCG) heterologous prime-boost
Author: Elodie Belnoue, Alexis Vogelzang, Natalie E. Nieuwenhuizen, Magdalena A. Krzyzaniak, Stephanie Darbre, Mario Kreutzfeldt, Ingrid Wagner, Doron Merkler, Paul-Henri Lambert, Stefan H. E. Kaufmann, Claire-Anne Siegrist and Daniel D. Pinschewer
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