Vaccines are proving to be highly effective in controlling hospitalization and deaths associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as shown by clinical trials and real-world evidence. However, a deadly second wave of coronavirus disease 2019 (COVID-19), infected by SARS-CoV-2 variants, especially the Delta (B.1.617.2) variant, with an increased number of post-vaccination breakthrough infections were reported in the world recently. Actually, Delta variant not only resulted in a severe surge of vaccine breakthrough infections which was accompanied with high viral load and transmissibility, but also challenged the development of effective vaccines. Therefore, the biological characteristics and epidemiological profile of Delta variant, the current status of Delta variant vaccine breakthrough infections and the mechanism of vaccine breakthrough infections were discussed in this article. In addition, the significant role of the Delta variant spike (S) protein in the mechanism of immune escape of SARS-CoV-2 was highlighted in this article. In particular, we further discussed key points on the future SARS-CoV-2 vaccine research and development, hoping to make a contribution to the early, accurate and rapid control of the COVID-19 epidemic.
Glypican-3 (GPC3) is a key biomarker for early diagnosis of human hepatocellular carcinoma (HCC) due to its overexpression in most HCC tumor tissues. Recently, peptides with high affinity to GPC3 have attracted more attention because of their high biocompatibility, non-immunogenicity, fast clearing and easy modification. Herein, we have designed an innovative GPC3 targeting peptide (sequence: DYEMHLWWGTEL, denoted as IPA) by using structure-based virtual simulation. The higher binding abilities of IPA over the reported peptide (YP) were displayed on different cell lines, showing a positive correlation with GPC3 expressions, which were further verified by the GPC3 protein binding assay. The GPC3 targeting specificity of IPA was proved by peptide blocking and siRNA experiment. The localized anchor of peptide IPA on the cell membranes of HepG2 and Huh-7 with GPC3 overexpression confirmed the GPC3 binding capacity. By connecting a near-infrared dye MPA, the in vivo identification ability of IPA to GPC3 was also demonstrated on GPC3-positive (HepG2) and GPC3-negative (U87) xenograft-bearing mice. These results indicated that the designed IPA presented desirable GPC3 targeting ability, showing promising prospects in detecting the expression of GPC3 for HCC targeting imaging.
Background: Mycoplasma pneumoniae can be divided into different subtypes on the basis of the sequence differences of adhesive protein P1, but the relationship between different subtypes, macrolide resistance and clinical manifestations are still unclear. In the present study, we established a molecular beacon based real-time polymerase chain reaction (real-time PCR) p1 gene genotyping method, analyzed the macrolide resistance gene mutations and the relationship of clinical characteristics with the genotypes. Methods: A molecular beacon based real-time PCR p1 gene genotyping method was established, the mutation sites of macrolide resistance genes were analyzed by PCR and sequenced, and the relationship of clinical characteristics with the genotypes was analyzed. Results: The detection limit was 1–100 copies/reaction. No cross-reactivity was observed in the two subtypes. In total, samples from 100 patients with positive M. pneumoniae detection results in 2019 and 2021 were genotyped using the beacon based real-time PCR method and P1-1 M. pneumoniae accounted for 69.0%. All the patients had the A2063G mutation in the macrolide resistance related 23S rRNA gene. Novel mutations were also found, which were C2622T, C2150A, C2202G and C2443A mutations. The relationship between p1 gene genotyping and the clinical characteristics were not statistically related. Conclusion: A rapid and easy clinical application molecular beacon based real-time PCR genotyping method targeting the p1 gene was established. A shift from type 1 to type 2 was found and 100.0% macrolide resistance was detected. Our study provided an efficient method for genotyping M. pneumoniae, valuable epidemiological monitoring information and clinical treatment guidance to control high macrolide resistance.
29 October 2020 in Human Vaccines & Immunotherapeutics
The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still spreading globally. The scientific community is attempting to procure an effective treatment and prevention strategy for COVID-19. A rising number of vaccines for COVID-19 are being developed at an unprecedented speed. Development platforms include traditional inactivated or live attenuated virus vaccines, DNA or RNA vaccines, recombinant viral vector vaccines, and protein or peptide subunit vaccines. There are 23 vaccines in the clinical evaluation stage and at least 140 candidate vaccines in preclinical evaluation. In this review, we describe research regarding basic knowledge on the virus, updates on the animal models, current landscape of vaccines in clinical evaluation and updated research results on vaccine development. Safe and effective COVID-19 vaccines require further investigation.