Biomedical subjects

Yan Zhi

Publications and source records attributed to Yan Zhi.

7 recordsLinked to original sources

PubMed2026

Isolation and Characterization of a Naturally Occurring Brevundimonas vesicularis Strain Exhibiting High Phytoene Accumulation.

Phytoene, a colorless precursor of carotenoids, has attracted increasing attention because of its favorable bioavailability, antioxidant activity, and potential applications in functional foods, nutraceuticals, and animal nutrition. However, its industrial utilization remains limited by low natural abundance and the dependence of current production strategies on genetic engineering or metabolic pathway manipulation. In this study, we identified and characterized a naturally occurring Brevundimonas vesicularis strain (Bv-xms2024) exhibiting pronounced phytoene accumulation without genetic modification. The strain was comprehensively characterized using morphological, biochemical, molecular, genomic, metabolomic, and transcriptional analyses. Quantitative LC-MS/MS analysis demonstrated that Bv-xms2024 accumulated phytoene to 420.42 ± 98.11 μg/g dry biomass after 96 h of cultivation, substantially exceeding the levels of downstream carotenoids, including β-carotene and astaxanthin. Optimization of cultivation parameters identified 25 °C, pH 7.0, and 96 h as the optimal conditions for phytoene accumulation, while serial passaging confirmed stable production over 20 generations. Genome annotation identified the carotenoid biosynthetic gene repertoire, while RT-qPCR analysis revealed a temporal shift from early upregulation of crtE and crtB to later upregulation of downstream pathway genes, consistent with the observed phytoene-dominant carotenoid profile. Short-term tolerance evaluations in mice and chickens revealed no observable adverse effects under the tested conditions. Collectively, these findings identify Bv-xms2024 as a promising natural microbial resource for phytoene production and provide a basis for further process development and strain-level safety evaluation.

Brevundimonas vesicularis↗

PubMed2006

Heparin binding directs activation of T cells against adeno-associated virus serotype 2 capsid.

Activation of T cells to the capsid of adeno-associated virus (AAV) serotype 2 vectors has been implicated in liver toxicity in a recent human gene therapy trial of hemophilia B. To further investigate this kind of toxicity, we evaluated T-cell responses to AAV capsids after intramuscular injection of vectors into mice and nonhuman primates. High levels of T cells specific to capsids of vectors based on AAV2 and a phylogenetically related AAV variant were detected. Vectors from other AAV clades such as AAV8 (ref. 3), however, did not lead to activation of capsid-specific T cells. Through the generation of AAV2-AAV8 hybrids and the creation of site-directed mutations, we mapped the domain that directs the activation of T cells to the RXXR motif on VP3, which was previously shown to confer binding of the virion to heparan sulfate proteoglycan (HSPG). Evaluation of natural and engineered AAV variants showed direct correlations between heparin binding, uptake into human dendritic cells (DCs) and activation of capsid-specific T cells. The role of heparin binding in the activation of CD8(+) T cells may be useful in modulating the immunogenicity of antigens and improving the safety profile of existing AAV vectors for gene therapy.

Animals↗

PubMed2006

Efficacy of severe acute respiratory syndrome vaccine based on a nonhuman primate adenovirus in the presence of immunity against human adenovirus.

Replication-deficient human adenovirus type 5 (AdH5) vectors can induce strong transgene product-specific cellular and humoral responses. However, many adult humans have neutralizing antibodies (NAbs) against AdH5 as a result of natural infection with this virus. Therefore, a chimpanzee adenovirus C7 (AdC7) vector was developed to circumvent interference by preexisting immunity to AdH5. This study evaluated the impact of preexisting immunity to human adenovirus on the efficacy of adenovirus-based vaccines against the coronavirus that causes severe acute respiratory syndrome (SARS-CoV). Efficacy was assessed after intramuscular injection of the vector into mice and was measured as the frequency of SARS-CoV-specific T cells and NAbs against SARS-CoV. Immunogenicity of the AdH5-based vaccine was significantly attenuated or completely abolished when the preexisting anti-AdH5 NAb titer was higher than 40. Because 27% of human serum samples from the United States tested so far have an anti-AdH5 NAb titer higher than 40, our results suggested that a significant percentage of humans with preexisting anti-AdH5 immunity would not be candidates for vaccination with an AdH5-based genetic vaccine. In contrast, preexisting anti-AdH5 NAbs have a minimal effect on the potency of the AdC7-based genetic vaccine. Taken together, our studies warrant the further development of AdC7 as a vaccine carrier for human trials.

Adenoviruses, Human↗

PubMed2006

Generation of an adenoviral vaccine vector based on simian adenovirus 21.

Adenoviral vectors can be used to generate potent humoral and cellular immune responses to transgene products. Use of adenoviral vectors based on non-human isolates may allow for their utilization in populations harbouring neutralizing antibodies to common human serotypes. A vector chimera was constructed using simian adenovirus 22 (a serotype belonging to the species Human adenovirus E) and simian adenovirus 21 (a serotype belonging to the species Human adenovirus B) expressing the Ebola (Zaire) virus glycoprotein (Ad C5/C1-ZGP). This chimeric adenovirus vector was used as a model to test its efficacy as a genetic vaccine and comparisons were made to a vector based on the commonly used human adenovirus C serotype 5 (Adhu5-ZGP). Ebola glycoprotein-specific T- and B-cell responses were measured in B10BR mice vaccinated with either Adhu5-ZGP or Ad C5/C1-ZGP vectors. Both vectors resulted in Ebola glycoprotein-specific gamma interferon-expressing T cells, although the Ad C5/C1-ZGP vector appeared to induce lower frequencies with kinetics slower than those elicited by the Adhu5-ZGP vector. The total immunoglobulin G response to Ebola glycoprotein was similar in sera from mice vaccinated with either vector. Two rhesus macaques vaccinated with the Ad C5/C1-ZGP vector were found to mount T-cell and antibody responses to the Ebola glycoprotein. It was found that a single administration of the chimeric Ad C5/C1-ZGP vector protected mice against a lethal challenge with a mouse-adapted strain of the Ebola (Zaire) virus.

Adenoviruses, Simian↗

PubMed2005

Chimpanzee adenovirus vaccine protects against Zaire Ebola virus.

This study evaluated the use of a chimpanzee-based adenovirus vaccine in mouse and Guinea pigs models of Zaire Ebola virus (ZEBOV) infection. Vaccine vector expressing the envelope glycoprotein of ZEBOV was created from the molecular clone of chimpanzee adenovirus pan7 (AdC7). AdC7 vaccine stimulated robust T and B cell responses to ZEBOV in naïve mice inducing complete protection to an otherwise lethal challenge of ZEBOV. Complete protection to Zaire Ebola virus was also observed in Guinea pigs vaccinated with a relatively low dose of AdC7 (5 x 10(9)/kg). Pre-existing immunity to AdHu5 was generated in mice following pre-exposure to AdHu5 or administration of pooled human immune globulin. Pre-existing immunity to human adenoviruses severely compromised the efficacy of the human AdHu5 vaccine but not the chimpanzee AdC7 vaccine. These results validate further development of Chimpanzee-based vaccine and highlight the impact of pre-existing immunity to the vaccine carrier.

Adenoviruses, Human↗

PubMed2005

Identification of murine CD8 T cell epitopes in codon-optimized SARS-associated coronavirus spike protein.

The causative agent of severe acute respiratory syndrome (SARS) has been identified as a new type of coronavirus, SARS-associated coronavirus (SARS-CoV). CD8 T cells play an important role in controlling diseases caused by other coronaviruses and in mediating vaccine-induced protective immunity in corresponding animal models. The spike protein, a main surface antigen of SARS-CoV, is one of the most important antigen candidates for vaccine design. Overlapping peptides were used to identify major histocompatibility complex class I-restricted epitopes in mice immunized with vectors encoding codon-optimized SARS-CoV spike protein. CD8 T-cell responses were mapped to two H-2(b)-restricted epitopes (S436-443 and S525-532) and one H-2(d)-restricted epitope (S366-374). The identification of these epitopes will facilitate the evaluation of vaccine strategies in murine models of SARS-CoV infection. Furthermore, codon and promoter optimizations can greatly enhance the overall immunogenicity of spike protein in the context of replication-defective human and simian adenoviral vaccine carriers. The optimized recombinant adenoviral vaccine vectors encoding spike can generate robust antigen-specific cellular immunity in mice and may potentially be useful for control of SARS-CoV infection.

Adenoviruses, Human↗

PubMed2005

SARS vaccine: progress and challenge.

Severe acute respiratory syndrome (SARS) emerged in 2002 as a severe and highly contagious infectious disease that rapidly spread to a number of different countries. The collaborative efforts of the global scientific community have provided, within a short period of time, substantial insights into the molecular biology and immunology of SARS-CoV. Although the outbreak has been contained, there is continuous concern that the virus may resurface into the human population through seasonal changes, animal reservoirs or laboratory accidents. The severe morbidity and mortality associated with SARS make it imperative that an effective vaccine be developed to prevent reemergence and epidemics in the future.

Animals↗