Biology subjects

Potchen, N.

Publications and source records attributed to Potchen, N..

2 recordsLinked to original sources

bioRxiv2024

Bacterial vaginosis-driven changes in vaginal T cell phenotypes and their implications for HIV susceptibility

Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome that is prevalent among reproductive-age females worldwide. Adverse health outcomes associated with BV include an increased risk of sexually-acquired HIV, yet the immunological mechanisms underlying this association are not well understood. To investigate BV-driven changes to cervicovaginal tract (CVT) and circulating T cell phenotypes, participants with or without BV provided vaginal tract (VT) and ectocervical (CX) tissue biopsies and PBMC samples. High-parameter flow cytometry revealed an increased frequency of cervical conventional CD4+ T cells (Tconv) expressing CCR5. However, we found no difference in number of CD3+CD4+CCR5+ cells in the CX or VT of BV+ vs BV- individuals, suggesting that BV-driven increased HIV susceptibility may not be solely attributed to increased CVT HIV target cell abundance. Flow cytometry also revealed that individuals with BV have an increased frequency of dysfunctional CX and VT CD39+ Tconv and CX tissue-resident CD69+CD103+ Tconv, reported to be implicated in HIV acquisition risk and replication. Many soluble immune factor differences in the CVT further support that BV elicits diverse and complex CVT immune alterations. Our comprehensive analysis expands on potential immunological mechanisms that may underlie the adverse health outcomes associated with BV including increased HIV susceptibility.

immunology↗

bioRxiv2023

The Regulation of Nucleic Acid Vaccine Responses by the Microbiome

SummaryNucleic acid vaccines, including both RNA and DNA platforms, are key technologies that have considerable promise in combating both infectious disease and cancer. However, little is known about the extrinsic factors that regulate nucleic acid vaccine responses and which may determine their effectiveness. The microbiome is recognized as a significant regulator of immune development and response, whose role in regulating some traditional vaccine platforms has recently been discovered. Using germ-free and specific-pathogen-free mouse models in combination with different protein, DNA, and mRNA vaccine regimens, we demonstrate that the microbiome is a significant regulator of nucleic acid vaccine immunogenicity. While the presence of the microbiome enhances CD8+ T cell responses to mRNA lipid nanoparticle (LNP) immunization, the microbiome suppresses immunoglobulin and CD4+ T cell responses to DNA-prime, DNA-protein-boost immunization, indicating contrasting roles for the microbiome in the regulation of these different nucleic acid vaccine platforms. In the case of mRNA-LNP vaccination, germ-free mice display reduced dendritic cell/macrophage activation that may underlie the deficient vaccine response. Our study identifies the microbiome as a relevant determinant of nucleic acid vaccine response with implications for their continued therapeutic development and deployment.

immunology↗