Intravenous BCG induces a more potent airway and lung immune response than intradermal BCG in SIV-infected macaques.
Solomon JauroErica C LarsonJanelle L GleimBrendon M WahlbergMark A RodgersJulia C ChehabAlondra E Lopez-VelazquesCassaundra L AmeelJaime A TomkoJennifer L SakalTodd DeMarcoH Jake BorishPauline MaielloE Lake PotterMario RoedererPhilana Ling LinJoAnne L FlynnCharles A ScangaPublished in: bioRxiv : the preprint server for biology (2024)
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is one of the leading causes of death due to an infectious agent. Coinfection with HIV exacerbates Mtb infection outcomes in people living with HIV (PLWH). Bacillus Calmette-Guérin (BCG), the only approved TB vaccine, is effective in infants, but its efficacy in adolescents and adults is limited. Here, we investigated the immune responses elicited by BCG administered via intravenous (IV) or intradermal (ID) routes in Simian Immunodeficiency Virus (SIV)-infected Mauritian cynomolgus macaques (MCM) without the confounding effects of Mtb challenge. We assessed the impact of vaccination on T cell responses in the airway, blood, and tissues (lung, thoracic lymph nodes, and spleen), as well as the expression of cytokines, cytotoxic molecules, and key transcription factors. Our results showed that IV BCG induces a robust and sustained immune response, including tissue-resident memory T (T RM ) cells in lungs, polyfunctional CD4+ and CD8αβ+ T cells expressing multiple cytokines, and CD8αβ+ T cells and NK cells expressing cytotoxic effectors in airways. We also detected higher levels of mycobacteria-specific IgG and IgM in the airways of IV BCG-vaccinated MCM. Although IV BCG vaccination resulted in an influx of T RM cells in lungs of MCM with controlled SIV replication, MCM with high plasma SIV RNA (>10 5 copies/mL) typically displayed reduced T cell responses, suggesting that uncontrolled SIV or HIV replication would have a detrimental effect on IV BCG-induced protection against Mtb.
Keyphrases
- mycobacterium tuberculosis
- immune response
- pulmonary tuberculosis
- induced apoptosis
- lymph node
- antiretroviral therapy
- hiv infected
- cell cycle arrest
- transcription factor
- nk cells
- hiv positive
- dendritic cells
- human immunodeficiency virus
- cystic fibrosis
- poor prognosis
- hiv aids
- oxidative stress
- emergency department
- spinal cord
- high dose
- young adults
- gene expression
- cell death
- physical activity
- patient safety
- toll like receptor
- working memory
- south africa
- dna binding
- diabetic rats
- long non coding rna
- endothelial cells
- mass spectrometry
- bacillus subtilis