Project description:To determine the blood transcriptional response to intravenous (IV) BCG vaccination in rhesus macaques and identify correlates of vaccine-mediated protection against Mycobacterium tuberculosis (Mtb) challenge.
Project description:To determine the blood transcriptional response to BCG vaccination administered via different routes in rhesus macaques and identify correlates of vaccine-mediated protection against Mycobacterium tuberculosis (Mtb) challenge.
Project description:Vaccination against tuberculosis by intradermal Bacillus Calmette-Guérin (BCG) injection saves many lives, supposedly by inducing adaptive immune memory in lymphocytes. Epidemiologically, BCG vaccination is also associated with reduced childhood mortality unrelated to TB, which is attributed to innate immune memory, also termed trained immunity. We recently demonstrated improved protection against tuberculosis infection in highly susceptible rhesus macaques by mucosal BCG vaccination, correlating with a unique local but no peripheral immune profile. Here, we investigated local and peripheral innate immune function after intradermal versus mucosal vaccination with M. bovis BCG or the live attenuated, M. tuberculosis-derived candidate, MTBVAC. The results demonstrate an augmented frequency of trained immunity in monocytes after respiratory mucosal administration of live attenuated mycobacterial vaccines compared to intradermal immunization, with MTBVAC being equally potent as BCG. These results provide further support to strategies for improving TB vaccination and, more broadly, modulating innate immunity via mucosal surfaces.
Project description:Vaccination triggers the production of antigen-specific antibodies, including IgG. IgG molecules are glycosylated at the Fc region, and these glycan modifications markedly influence Fc receptor binding and downstream immune functions. Notably, infections with enveloped viruses such as SARS-CoV-2 can trigger the production of afucosylated IgG, which enhances FcγRIIIa binding and promotes antibody-dependent cellular cytotoxicity. Despite its importance, the glycosylation profiles of antigen-specific IgG following vaccination remain understudied, particularly in animal models. In this study, we investigated the Fc glycosylation patterns of antigen-specific IgG in hamsters and rhesus macaques following immunization with the Ad26.COV2.S COVID-19 vaccine. Overall, our findings demonstrate that IgG Fc glycosylation dynamics in these animal models largely parallel those in humans. For example, we observed a transient afucosylated IgG response in both species, resembling the response previously reported in humans. These results indicate that IgG Fc glycosylation responses to vaccination in macaques and hamsters recapitulate key features of the human response, supporting their use as translational models for adenovirus vector-based vaccination studies.
Project description:The century-old Mycobacterium bovis Bacillus Calmette-Guerin (BCG) remains the only licensed vaccine against tuberculosis (TB). Despite this, there is still a lot to learn about the immune response induced by BCG, both in terms of phenotype and specificity. Here, we investigated the BCG-specific gene expression changes induced in PBMCs and CD4 memory T cells by BCG in individuals pre- and 8m post vaccination. We also determined whether reactivity against a peptide pool defined in individuals with controlled latent TB infection (MTB300), and with peptides homologous to peptides found in BCG, was boosted following BCG vaccination.
Project description:Rhesus macaques vaccinated by rhesus cytomegalovirus vectors expressing simian immunodeficiency virus proteins (RhCMV/SIV) activate gene expression signature associated with IL15. To examine the gene expression signature activated by IL15, we performed longitudinal examinations of rhesus macaques during IL15 treament.
Project description:This SuperSeries is composed of the following subset Series: GSE33090: Dramatic effects of social behavior on gene regulation in rhesus macaques [Individual_expression] GSE34127: Dramatic effects of social behavior on gene regulation in rhesus macaques [Cell type_expression] GSE34128: Dramatic effects of social behavior on gene regulation in rhesus macaques [Bisulfite_seq] Refer to individual Series
Project description:Single cell RNA sequencing analysis was performed on bronchoalveolar lavage samples obtained from Rhesus macaques infected intranasally/intratracheally with SARS-CoV-2 after vaccination with mRNA-1273 vaccine
