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Replication-Deficient Lymphocytic Choriomeningitis Virus-Vectored Vaccine Candidate for the Induction of T Cell Immunity against <i>Mycobacterium tuberculosis</i>
oleh: 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, Daniel D. Pinschewer
Format: | Article |
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Diterbitkan: | MDPI AG 2022-02-01 |
Deskripsi
<i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) 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 <i>Mtb</i> antigens TB10.4 and Ag85B. In mice, rLCMV elicited high frequencies of polyfunctional <i>Mtb</i>-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 <i>Mtb</i> 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 <i>Mtb</i> challenge. When combining rLCMV with BCG vaccination in a heterologous prime-boost regimen, responses to the rLCMV-encoded <i>Mtb</i> 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.