COVID-19 vaccine candidates and vaccine development platforms available worldwide / 药物分析学报

The pandemic caused by the worldwide spread of the coronavirus,which first appeared in 2019,has been named coronavirus disease 19 (COVID-19).More than 4.5 million deaths have been recorded due to the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),according to the World Health Organization.COVID-19 Dashboard in September 2021.Apart from the wildtype,other variations have been successfully transmitted early in the outbreak although they were not discovered until March 2020.Modifications in the SARS-CoV-2 genetic material,such as mutation and recombi-nation,have the ability to modify the viral life span,along with transitivity,cellular tropism,and symptom severity.Several processes are involved in introducing novel vaccines to the population,including vaccine manufacturing,preclinical studies,Food and Drug Administration permission or cer-tification,processing,and marketing.COVID-19 vaccine candidates have been developed by a number of public and private groups employing a variety of strategies,such as RNA,DNA,protein,and viral vectored vaccines.This comprehensive review,which included the most subsequent evidence on unique features of SARS-CoV-2 and the associated morbidity and mortality,was carried out using a systematic search of recent online databases in order to generate useful knowledge about the COVID-19 updated versions and their consequences on the disease symptoms and vaccine development.

Functional effects of a tandem duplication polymorphism in the 5'flanking region of the DRD4 gene.

BACKGROUND: Several polymorphisms have been identified in the 5'flanking region of the human dopamine D(4) receptor gene (DRD4), including a tandem duplication polymorphism. This comprises a 120-base-pair repeat sequence that is known to have different allele frequencies in various populations around the world. Furthermore, various studies have revealed evidence of linkage to attention-deficit/hyperactivity disorder and association with schizophrenia and methamphetamine abuse. The location of the polymorphism in the 5'regulatory region of the DRD4 gene and the fact that it consists of potential transcription factor binding sites suggest that it might confer differential transcriptional activity of the alleles. METHODS: We investigated the functional effects of this gene variant with transient transfection methods in four human cell lines and then assessed transcriptional activity with luciferase reporter gene assays. RESULTS: The longer allele has lower transcriptional activity than the shorter allele in SK-N-MC, SH-SY5Y, HEK293, and HeLa cell lines. CONCLUSIONS: This evidence suggests that the duplication might have a role in regulating the expression of the DRD4 gene and provides an understanding of the biological mechanisms underlying the etiology of neuropsychiatric disorders such as ADHD, schizophrenia, and metamphetamine abuse.

Joint analysis of the DRD5 marker concludes association with attention-deficit/hyperactivity disorder confined to the predominantly inattentive and combined subtypes.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable, heterogeneous disorder of early onset, consisting of a triad of symptoms: inattention, hyperactivity, and impulsivity. The disorder has a significant genetic component, and theories of etiology include abnormalities in the dopaminergic system, with DRD4, DAT1, SNAP25, and DRD5 being implicated as major susceptibility genes. An initial report of association between ADHD and the common 148-bp allele of a microsatellite marker located 18.5 kb from the DRD5 gene has been followed by several studies showing nonsignificant trends toward association with the same allele. To establish the postulated association of the (CA)(n) repeat with ADHD, we collected genotypic information from 14 independent samples of probands and their parents, analyzed them individually and, in the absence of heterogeneity, analyzed them as a joint sample. The joint analysis showed association with the DRD5 locus (P=.00005; odds ratio 1.24; 95% confidence interval 1.12-1.38). This association appears to be confined to the predominantly inattentive and combined clinical subtypes.

Association analysis of MAOA and COMT with neuroticism assessed by peers.

There are several reported associations between depressive disorders, panic disorder, and obsessive-compulsive disorder (OCD) and a variety of polymorphisms in the monoamine oxidase A (MAOA) gene. Associations have also been reported between the catechol-O-methyltransferase (COMT) gene and both OCD and bipolar depression. However, the role of these markers has not been explored for the personality trait of neuroticism (N), a normally distributed quantitative trait, which is highly genetically correlated with anxiety and depression and may be a vulnerability to either type of disorder. We explored the possible role of MAOA, COMT, and their interaction on N using a selected extremes design. From a sample of 2,085 individuals, each assessed for N by two independent peers rather than using self-report questionnaires, we selected 57 individuals from the top 10% of scores, and 62 individuals from the bottom 10%. Using selected extreme low subjects as the controls, rather than an unselected control group gives roughly twice the power of a standard case-control design. We typed a functional variable number tandem repeat (VNTR) in the MAOA gene promoter, and a functional polymorphism in the coding region of the COMT gene. Two novel alleles in the MAOA VNTR were identified on the basis of their size, and their structure examined by sequencing analysis. We found weak evidence for association with COMT genotype, when the females and males were considered separately, and for MAOA genotype in males only. There was no significant interaction between COMT and MAOA.

Evaluation of the genes for the adrenergic receptors alpha 2A and alpha 1C and Gilles de la Tourette Syndrome.

Gilles de la Tourette Syndrome (GTS) has long been known to be familial, and evidence from twin studies indicates that it has a substantial genetic component. Our genome scan of sibling pair families with GTS found evidence suggestive of linkage to several chromosomal locations. On the basis of these findings, we have begun to study additional markers in these regions, with some of the markers located in candidate genes. Two candidate genes stand out in these regions: the adrenergic receptor alpha 1C(1A) (ADRA1C) located on chromosome 8p and the adrenergic receptor alpha 2A (ADRA2A) located on chromosome 10q. The adrenergic system has been suggested to play a role in GTS based on the reduction of symptoms with the adrenergic receptor agonists, clonidine and guanfacine. We examined the inheritance of polymorphisms in the ADRA2A and ADRA1C genes in 113 nuclear families identified through a GTS proband. We found no significant evidence for linkage using the transmission disequilibrium test for these two genes. Based on our families, we conclude that these genes are not major genetic factors contributing to the susceptibility to GTS.