Late gene expression–deficient cytomegalovirus vectors elicit conventional T cells that do not protect against SIV

Hansen, Scott G.; Womack, Jennie; Perez, Wilma; Schmidt, Kimberli A.; Marshall, Emily E.; Iyer, Ravi; Cleveland-Rubeor, Hillary C.; Otero, Claire E.; Taher, Husam; Burgt, Nathan H. Vande; Barfield, Richard; Randall, Kurt T.; Morrow, David W.; Hughes, Colette M.; Selseth, Andrea N.; Gilbride, Roxanne M.; Ford, Julia C.; Caposio, Patrizia; Tarantal, Alice F.; Chan, Cliburn; Malouli, Daniel; Barry, Peter A.; Permar, Sallie R.; Picker, Louis J.; Frueh, Klaus

doi:10.1172/jci.insight.164692

Cited by 8 publications

(2 citation statements)

References 56 publications

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“…Rhesus macaques, a non-human primate species, have been widely used in recent years for researching human diseases. For instance, they have been used in cytomegalovirus model 25 and Ebola virus model 26 , Alzheimer’s disease model 27 , liver disease model 28 , and type 2 diabetes model 29 . As the understanding of the mechanisms involving intestinal microbiota has advanced, scientists have discovered its association with the development of various diseases 30 .…”

Section: Discussionmentioning

confidence: 99%

Metagenomic comparison of intestinal microbiota between normal and liver fibrotic rhesus macaques (Macaca mulatta)

Wei,

Li,

Zhu

et al. 2024

Sci Rep

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Liver fibrosis is an important pathological process in chronic liver disease and cirrhosis. Recent studies have found a close association between intestinal microbiota and the development of liver fibrosis. To determine whether there are differences in the intestinal microbiota between rhesus macaques with liver fibrosis (MG) and normal rhesus macaques (MN), fecal samples were collected from 8 male MG and 12 male MN. The biological composition of the intestinal microbiota was then detected using 16S rRNA gene sequencing. The results revealed statistically significant differences in ASVs and Chao1 in the alpha-diversity and the beta-diversity of intestinal microbiota between MG and MN. Both groups shared Prevotella and Lactobacillus as common dominant microbiota. However, beneficial bacteria such as Lactobacillus were significantly less abundant in MG (P = 0.02). Predictive functional analysis using PICRUSt2 gene prediction revealed that MG exhibited a higher relative abundance of functions related to substance transport and metabolic pathways. This study may provide insight into further exploration of the mechanisms by which intestinal microbiota affect liver fibrosis and its potential future use in treating liver fibrosis.

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Section: Discussionmentioning

confidence: 99%

Metagenomic comparison of intestinal microbiota between normal and liver fibrotic rhesus macaques (Macaca mulatta)

Wei,

Li,

Zhu

et al. 2024

Sci Rep

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“…First, based on extensive work on rhCMV strain RhCMV68-1, vaccines with RhCMV68-1 expressing SIV immunogens elicited high magnitude, broad effector memory (TEM)-skewed CD8 + T cell responses in the absence of an antibody response in 100% of animals, and demonstrated arrest and clearance of SIV in nearly 60% of vaccinated rhesus macaques, with similar efficacy maintained in CMV seropositive animals [ 28 , 29 ▪▪ , 30 , 31 ▪ , 56 ▪ , 100 ]. Second, the RhCMV68-1 vaccine generates unconventional MHC-E-restricted HIV-specific CD8 + T cells [ 31 ▪ , 56 ▪ , 101 ]. MHC-E is highly conserved and has limited polymorphism compared to classical MHC-I, thus potentially increasing the likelihood that conserved epitopes could be found when adapting the CMV platform for use in humans [ 29 ▪▪ , 102 ].…”

Section: T Cell-based Vaccine Delivery Platformsmentioning

confidence: 99%

Generating and measuring effective vaccine-elicited HIV-specific CD8+ T cell responses

Borgo,

Rutishauser

2023

Current Opinion in HIV and AIDS

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Purpose of review There is growing consensus that eliciting CD8+ T cells in addition to antibodies may be required for an effective HIV vaccine for both prevention and cure. Here, we review key qualities of vaccine-elicited CD8+ T cells as well as major CD8+ T cell-based delivery platforms used in recent HIV vaccine clinical trials. Recent findings Much progress has been made in improving HIV immunogen design and delivery platforms to optimize CD8+ T cell responses. With regards to viral vectors, recent trials have tested newer chimp and human adenovirus vectors as well as a CMV vector. DNA vaccine immunogenicity has been increased by delivering the vaccines by electroporation and together with adjuvants as well as administering them as part of a heterologous regimen. In preclinical models, self-amplifying RNA vaccines can generate durable tissue-based CD8+ T cells. While it may be beneficial for HIV vaccines to recapitulate the functional and phenotypic features of HIV-specific CD8+ T cells isolated from elite controllers, most of these features are not routinely measured in HIV vaccine clinical trials. Summary Identifying a vaccine capable of generating durable T cell responses that target mutationally vulnerable epitopes and that can rapidly intercept infecting or rebounding virus remains a challenge for HIV. Comprehensive assessment of HIV vaccine-elicited CD8+ T cells, as well as comparisons between different vaccine platforms, will be critical to advance our understanding of how to design better CD8+ T cell-based vaccines for HIV.

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Programming cytomegalovirus as an HIV vaccine

Picker¹,

Lifson²,

Gale³

et al. 2023

Trends in Immunology

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Late gene expression–deficient cytomegalovirus vectors elicit conventional T cells that do not protect against SIV

Cited by 8 publications

References 56 publications

Metagenomic comparison of intestinal microbiota between normal and liver fibrotic rhesus macaques (Macaca mulatta)

Metagenomic comparison of intestinal microbiota between normal and liver fibrotic rhesus macaques (Macaca mulatta)

Generating and measuring effective vaccine-elicited HIV-specific CD8+ T cell responses

Programming cytomegalovirus as an HIV vaccine

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