Natural killer cell transcriptomics following vaccinia virus infection of mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE225180 | GEO | 2023/02/13
REPOSITORIES: GEO
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Project description:Successful vaccination against smallpox with conventional vaccinia virus is usually determined by the development of a vesicular skin lesion at the site of vaccinia inoculation, called a ‘take’. Although previous vaccination is known to be associated with attenuation of the take, the immunology that underlies a no-take in vaccinia-naïve individuals is not well understood. We hypothesized that antibody profiling of individuals before and after receiving vaccinia would reveal differences between takes and no-takes that may help better understand the phenomenon. Using vaccinia proteome microarrays and recombinant protein ELISAs we first examined the antibody response in vaccinia-naïve individuals that failed to take after receiving different doses of the replication competent smallpox vaccines, DryVax® and APSV. Most that received diluted vaccine failed to respond, whereas 4 other no-takes receiving diluted vaccine, and 4 receiving undiluted vaccine, mounted an antibody response. Interestingly, their antibody profiles were not significantly different from controls that did show a take. However, we did find elevated antibody titers in no-takes prior to receiving DryVax® that was significantly different from takes. Although the sample size studied was small, we conclude the failure to take in responders correlates with pre-existing immunity of unknown etiology that may attenuate the skin reaction in a way similar to previous smallpox vaccination. Antibody profiling was peformed on sera from vaccinees receiving smallpox vaccines, either Wyeth DryVax or Aventis Pasteur Vaccine ('WetVax') in NIH-sponsored clinical trials. These samples comprise 23 vaccinia naïve no-takes, and 50 vaccinia naïve takes and 25 previoulsy vaccinated takes as controls. Samples from d0 (day of vaccination) and at the peak of the antibody repsonse (d28) were taken from each donor and probed in triplicate against the proteome arrays.
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Project description:Transcriptional analysis of global gene expression changes in naïve subjects in response to smallpox vaccination with either DryVax or the replication-competent, attenuated LC16m8 vaccinia virus.
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Project description:Successful vaccination against smallpox with conventional vaccinia virus is usually determined by the development of a vesicular skin lesion at the site of vaccinia inoculation, called a ‘take’. Although previous vaccination is known to be associated with attenuation of the take, the immunology that underlies a no-take in vaccinia-naïve individuals is not well understood. We hypothesized that antibody profiling of individuals before and after receiving vaccinia would reveal differences between takes and no-takes that may help better understand the phenomenon. Using vaccinia proteome microarrays and recombinant protein ELISAs we first examined the antibody response in vaccinia-naïve individuals that failed to take after receiving different doses of the replication competent smallpox vaccines, DryVax® and APSV. Most that received diluted vaccine failed to respond, whereas 4 other no-takes receiving diluted vaccine, and 4 receiving undiluted vaccine, mounted an antibody response. Interestingly, their antibody profiles were not significantly different from controls that did show a take. However, we did find elevated antibody titers in no-takes prior to receiving DryVax® that was significantly different from takes. Although the sample size studied was small, we conclude the failure to take in responders correlates with pre-existing immunity of unknown etiology that may attenuate the skin reaction in a way similar to previous smallpox vaccination.
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