Ontology highlight
ABSTRACT:
PROVIDER: PRJNA795093 | ENA |
REPOSITORIES: ENA
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Project description:Live-attenuated viral vaccines have been successfully used to combat infectious disease for decades but due to their empirical derivation, little is known about their mechanisms of attenuation. This lack of understanding makes the development of next generation live attenuated vaccines difficult. The success of the 17D vaccine and availability of the parent virus, Asibi, makes it an excellent model to understand the molecular basis of attenuation of a live attenuated vaccine and the effects of viral diversity on vaccine function. Due to the differences in genetic diversity between WT Asibi virus and its 17D vaccine derivative, we investigated the changes in genetic diversity of 17D and Asibi viruses following treatment with ribavirin.
2020-01-01 | E-MTAB-8504 | biostudies-arrayexpress
Project description:Zika virus (ZIKV) is a mosquito-transmitted positive-sense RNA virus in the family Flaviviridae. Live attenuated vaccines have been successfully used to combat infection by flaviviruses, such as yellow fever and Japanese encephalitis viruses. A Zika virus harboring combined mutations in the envelope protein glycosylation site and in the nonstructural 4B protein amino acid 36 (ZE4B-36) was generated and assessed for stability, attenuation, and protection against infection. To determine the genetic stability of its RNA genome, ZE4B-36 was serially passaged in vitro in Vero cells. Virus harvested from passages (P)1 to P6 was subjected to next generation sequencing and downstream analysis to determine its nucleotide sequence variability. Specifically, single nucleotide variant analysis showed that the ZE4B-36 genome decreased its genetic diversity and resulted in a more stable nucleotide sequence. Thus, in addition to showing attenuation and protection, ZE4B-36 is a stable live attenuated virus that possesses characteristics important for a vaccine to combat Zika disease.
2021-12-31 | E-MTAB-9496 | biostudies-arrayexpress
Project description:With the advent of advanced sequencing technology, studies of RNA viruses have shown that genetic diversity contribute to both attenuation and virulence. The differences in genetic diversity of wild-type Asibi virus and 17D-204 vaccine provides an unique opportunity to investigate RNA population theory in the context of a well described live attenuated vaccine. Utilizing infectious clone-derived viruses containing some of the amino acid substitutions that differentiate yellow fever wild-type Asibi strain from 17D vaccine and recovered in a controlled experiment, establishes that the genetic diversity differences that exist between wild-type Asibi and 17D-204 vaccine viruses are not influenced by either different passage history or source of samples, but rather resulted from the attenuation of wild-type Asibi virus to yield the 17D vaccine sub-strains.
2018-10-16 | E-MTAB-6614 | biostudies-arrayexpress
Project description:To understand the mechanistic basis of local innate and adaptive immunity against infectious bronchitis virus (IBV) at the molecular level, we examined the gene transcription profile of tracheal epithelial layers at 3 days after infection of chickens with an attenuated IBV-Massachusetts strain. Keywords: Disease State Analysis, Early mucosal immune response, FHCRC 13k chicken array
2006-11-03 | GSE6211 | GEO
Project description:Very few live attenuated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are currently in pre-clinical or clinical development. We rationally attenuated SARS-CoV-2 (isolate WA1/2020) by removing the polybasic cleavage site within the spike protein and the open reading frames (ORFs) 6-8, and by introducing a pair of mutations into the non-structural protein 1 (Nsp1). The derived virus (WA1-DPRRA-ORF6-8-Nsp1K164A/H165A) became severely attenuated in both the K18-human ACE2 (hACE2) transgenic mice and in Syrian hamsters. Transcriptomic profiling of nasal turbinates and lung tissues of infected Syrian hamsters confirmed that WA1-DPRRA-ORF6-8-Nsp1K164A/H165A attenuated the upregulation of proinflammatory pathways. A single intranasal immunization of just 100 PFU of the WA1-DPRRA-ORF6-8-Nsp1K164A/H165A elicited binding and neutralizing antibody responses in Syrian hamsters and completely protected against SARS-CoV-2-induced weight loss and pneumonia. These data demonstrate the feasibility of rational attenuation of SARS-CoV-2. WA1-DPRRA-ORF6-8-Nsp1K164A/H165A represents a promising live attenuated vaccine candidate.
2022-04-04 | GSE199922 | GEO
Project description:Live attenuated vaccines are often superior to dead vaccines, yet the immunological mechanisms remain largely obscure. We have recently uncovered an inherent capacity of antigen-presenting cells (APC) to discriminate live from killed bacteria by virtue of vita-PAMPs. Here we found that innate recognition of bacterial viability strongly promotes the differentiation of fully functional T follicular helper (TFH) cells. We identify TLR8 and its signaling adaptor MyD88 as critical sensor for bacterial viability in human APC, activation of which is required and sufficient to induce selective transcriptional remodeling and the production of TFH promoting signals like IL-12. Activators of other TLRs including licensed vaccine adjuvants fail to do so. Consequently, vita-PAMP receptors such as TLR8 represent promising targets for adjuvants to improve the efficacy of modern inanimate subunit vaccines. Human monocytes were infected with live or heat-killed E. coli for 6h.
2016-04-06 | E-GEOD-68255 | biostudies-arrayexpress
Project description:Ribosome profiling (Ribo-Seq) (maps positions of translating ribosomes on the transcriptome) and RNA-Seq (quantifies the transcriptome) analysis of chicken (Gallus gallus) cells infected with Infectious Bronchitis Virus (IBV) strains Beaudette and M41.
2019-06-18 | E-MTAB-7849 | biostudies-arrayexpress
Project description:Infectious hematopoietic necrosis virus (IHNV) is a virus of the genus Novirhabdovirus and the causative agent of infectious hematopoietic necrosis (IHN), one of the most serious threats to salmonid fishes. IHN outbreaks can cause more than 80% mortality rates in certain cases. Studying the transcriptional responses to the secondary immunization with a live attenuated IHNV vaccine will help us understand how fish previously immunized respond when they encounter again the same pathogen and how effective this type of vaccination is.This experiment was aimed at understanding the transcriptomic response of rainbow trout to an IHNV secondary nasal vaccination.
2022-02-18 | E-MTAB-4788 | biostudies-arrayexpress