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Severe acute respiratory syndrome coronavirus 2

ABSTRACT: A safe, effective and adaptable live-attenuated SARS-CoV-2 vaccine to reduce disease and transmission using one-to-stop genome modifications

PROVIDER: PRJNA1002985 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25549000_1.fastq.gz	Fastqsanger.gz
	SRR25549000_2.fastq.gz	Fastqsanger.gz
	SRR25549001_1.fastq.gz	Fastqsanger.gz
	SRR25549001_2.fastq.gz	Fastqsanger.gz
	SRR25549002_1.fastq.gz	Fastqsanger.gz

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Repurposing Live Attenuated Trivalent MMR Vaccine as Cost-effective Cancer Immunotherapy

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Transcriptional profiles of sorted CD8+ and CD4+ memory T cells from CP and NP and unvaccinated control RM 7 days prior to, and 4 and 14 days after wt SIVmac239 challenge by microarray analysis.

Project description:Live-attenuated SIV vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV/AIDS, yet the basis of their robust protection remains poorly understood. Here, we demonstrate that the degree of LAV-mediated protection against intravenous (IV) wildtype (wt) SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific, effector-differentiated T cells in lymph node (LN), but not with such T cell responses in blood or with other cellular, humoral and innate immune parameters. Maintenance of protective T cell responses was associated with persistent LAV replication in LN, which occurred almost exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid tissue-based, effector-differentiated, SIV-specific T cells that intercept and suppress early wt SIV amplification and, if present in sufficient frequencies, can completely control and perhaps clear infection -- an observation that provides rationale for development of safe, persistent vectors that can elicit and maintain such responses. There are two protection outcome groups, complete protect (CP) and non-protect (NP) animals. Memory T cells (CD4+ or CD8+) were sorted for three time points, seven days pre-challenge, four days post-challenge and fourteen days post-challenge.

2012-08-08 | E-GEOD-39968 | biostudies-arrayexpress

A recombination-resistant genome for live attenuated and stable PEDV vaccines by engineering the transcriptional regulatory sequences

Project description:Porcine epidemic diarrhea virus (PEDV) is a deadly coronavirus for neonatal piglets and no effective vaccines are available. Transcriptional regulatory sequences (TRSs) are critical in regulating coronavirus discontinuous transcription. Also, TRSs contribute to a high recombination rate of coronaviruses, leading to difficulty in developing safe live vaccines. We hypothesize that recoding the TRS core sequences (TRS-CS) of PEDV can make the recombination impossible between the engineered vaccine virus and field strains or wildtype viruses. We used an infectious clone-derived reporter PEDV, dORF3-EGFP, as the backbone to generate a remodeled TRS (RMT) mutant that carries the recoded leader and body TRS-CSs. The RMT and dORF3-EGFP showed comparable replication efficiency in Vero cells. However, the incompatibility between the rewired and wildtype TRS-CSs led to few EGFP in RMT-infected cells. Furthermore, RMT and dORF3-EGFP had a similar attenuated phenotype, replication efficiency, and protective immunogenicity in neonatal pigs. RNA sequencing analysis indicated that EGFP transcription directed by the heterogenous TRS-CSs was significantly reduced to an extremely low level. Meanwhile, recombinant viruses were not detected in Vero cells and in pigs that were co-infected with RMT and a PEDV S-INDEL strain, Iowa106. In vitro and in vivo passaging of the RMT did not result in reversion mutations in the rewired TRS-CSs, introduced gaps, and disrupted wildtype TRSs. In summary, the RMT mutant was resistant to recombination and genetically stable and can be further optimized (e.g., deletion of the EGFP) to serve as a platform to develop safe PEDV live attenuated vaccines.

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Project description:Live attenuated Lassa Virus Vaccine Candidate

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Project description:Live-attenuated SIV vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV/AIDS, yet the basis of their robust protection remains poorly understood. Here, we demonstrate that the degree of LAV-mediated protection against intravenous (IV) wildtype (wt) SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific, effector-differentiated T cells in lymph node (LN), but not with such T cell responses in blood or with other cellular, humoral and innate immune parameters. Maintenance of protective T cell responses was associated with persistent LAV replication in LN, which occurred almost exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid tissue-based, effector-differentiated, SIV-specific T cells that intercept and suppress early wt SIV amplification and, if present in sufficient frequencies, can completely control and perhaps clear infection -- an observation that provides rationale for development of safe, persistent vectors that can elicit and maintain such responses. There are four protection outcome groups: unvaccinated control (C), complete protect (CP), non-protect (NP) and partial protect (PP). Respectively for these groups, there are 7, 9, 6 and 4 animals sampled seven days pre-challenge (minus7PCD); 9, 13, 5 and 5 animals sampled four days post-challenge (4PCD) and 8, 11, 5 and 3 fourteen days post-challenge (14PCD).

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