Analysis of the protective efficacy of approved COVID-19 vaccines against Omicron variants and the prospects for universal vaccines.

By the end of 2022, different variants of Omicron had rapidly spread worldwide, causing a significant impact on the Coronavirus disease 2019 (COVID-19) pandemic situation. Compared with previous variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), these new variants of Omicron exhibited a noticeable degree of mutation. The currently developed platforms to design COVID-19 vaccines include inactivated vaccines, mRNA vaccines, DNA vaccines, recombinant protein vaccines, virus-like particle vaccines, and viral vector vaccines. Many of these platforms have obtained approval from the US Food and Drug Administration (FDA) or the WHO. However, the Omicron variants have spread in countries where vaccination has taken place; therefore, the number of cases has rapidly increased, causing concerns about the effectiveness of these vaccines. This article first discusses the epidemiological trends of the Omicron variant and reviews the latest research progress on available vaccines. Additionally, we discuss progress in the development progress and practical significance of universal vaccines. Next, we analyze the neutralizing antibody effectiveness of approved vaccines against different variants of Omicron, heterologous vaccination, and the effectiveness of multivalent vaccines in preclinical trials. We hope that this review will provide a theoretical basis for the design, development, production, and vaccination strategies of novel coronavirus vaccines, thus helping to end the SARS-CoV-2 pandemic.

The role of SARS-CoV-2 N protein in diagnosis and vaccination in the context of emerging variants: present status and prospects.

Despite many countries rapidly revising their strategies to prevent contagions, the number of people infected with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to surge. The emergent variants that can evade the immune response significantly affect the effectiveness of mainstream vaccines and diagnostic products based on the original spike protein. Therefore, it is essential to focus on the highly conserved nature of the nucleocapsid protein as a potential target in the field of vaccines and diagnostics. In this regard, our review initially discusses the structure, function, and mechanism of action of N protein. Based on this discussion, we summarize the relevant research on the in-depth development and application of diagnostic methods and vaccines based on N protein, such as serology and nucleic acid detection. Such valuable information can aid in designing more efficient diagnostic and vaccine tools that could help end the SARS-CoV-2 pandemic.

Detecting the Neuraminidase R294K Mutation in Avian Influenza A (H7N9) Virus Using Reverse Transcription Droplet Digital PCR Method.

The R294K mutation in neuraminidase (NA) causes resistance to oseltamivir in the avian influenza virus H7N9. Reverse transcription droplet digital polymerase chain reaction (RT-dd PCR) is a novel technique for detecting single-nucleotide polymorphisms. This study aimed to develop an RT-dd PCR method for detecting the R294K mutation in H7N9. Primers and dual probes were designed using the H7N9 NA gene and the annealing temperature was optimized at 58.0 °C. The sensitivity of our RT-dd PCR method was not significantly different from that of RT-qPCR (p = 0.625), but it could specifically detect R294 and 294K in H7N9. Among 89 clinical samples, 2 showed the R294K mutation. These two strains were evaluated using a neuraminidase inhibition test, which revealed that their sensitivity to oseltamivir was greatly reduced. The sensitivity and specificity of RT-dd PCR were similar to those of RT-qPCR and its accuracy was comparable to that of NGS. The RT-dd PCR method had the advantages of absolute quantitation, eliminating the need for a calibration standard curve, and being simpler in both experimental operation and result interpretation than NGS. Therefore, this RT-dd PCR method can be used to quantitatively detect the R294K mutation in H7N9.

Adenovirus Vaccine Containing Truncated SARS-CoV-2 Spike Protein S1 Subunit Leads to a Specific Immune Response in Mice.

The development of an efficient and safe coronavirus disease 2019 (COVID-19) vaccine is a crucial approach for managing the severe acute respiratory disease coronavirus 2 (SARS-CoV-2) pandemic in light of current conditions. In this study, we produced a shortened segment of the optimized SARS-CoV-2 spike gene (2043 bp, termed S1) that was able to encode a truncated S1 protein. The protein was tested to determine if it could elicit efficient immunization in mice against SARS-CoV-2. The presence of the S1 protein was confirmed with immunofluorescence and Western blotting. An adenovirus vaccine bearing the S1 gene fragment (Ad-S1) was administered intramuscularly to mice four times over 4 weeks. SARS-CoV-2 S1 protein humoral immunity was demonstrated in all immunized mice. The serum from immunized mice demonstrated excellent anti-infection activity in vitro. A robust humoral immune response against SARS-CoV-2 was observed in the mice after vaccination with Ad-S1, suggesting that the adenovirus vaccine may aid the development of vaccines against SARS-CoV-2 and other genetically distinct viruses.

Complex impacts of gallstone disease on metabolic syndrome and nonalcoholic fatty liver disease.

Background: Patients with gallstone disease (GSD) often have highly co-occurrence with metabolic syndrome (MetS) and Nonalcoholic fatty liver disease (NAFLD) both associated with insulin resistance (IR). Meanwhile, highly prevalence of NAFLD was found in patients who received cholecystectomy. However, the associations of GSD with MetS, NAFLD is inconsistent in the published literature. And risk of cholecystectomy on NAFLD is unclear. Methods: We searched the Medline EMBASE and WOS databases for literature that met our study topic. To be specific, studies with focus on associations between GSD and MetS/NAFLD, and risk evaluation on cholecystectomy and NAFLD incidence were enrolled for further analysis. The random effect model was used to calculate the combined relative ratio (RR) and odds ratio (OR)and 95% confidence interval (CI). Results: Seven and six papers with focus on connections between GSD and NAFLD/MetS prevalence. Correspondingly, seven papers with focus on risk of cholecystectomy on NAFLD occurrence were also enrolled into meta-analysis. After pooling the results from individual study, patients with GSD had higher risk of MetS (OR:1.45, 95%CI: 1.23-1.67, I2 = 41.1%, P=0.165). Risk of GSD was increased by 52% in NAFLD patients (pooled OR:1.52, 95%CI:1.24-1.80). And about 32% of increment on NAFLD prevalence was observed in patients with GSD (pooled OR: 1.32, 95%CI:1.14-1.50). With regard to individual MetS components, patients with higher systolic blood pressure were more prone to develop GSD, with combined SMD of 0.29 (96%CI: 0.24-0.34, P<0.05). Dose-response analysis found the GSD incidence was significantly associated with increased body mass index (BMI) (pooled OR: 1.02, 95%CI:1.01-1.03) in linear trends. Patients who received cholecystectomy had a higher risk of post-operative NAFLD (OR:2.14, 95%CI: 1.43-2.85), P<0.05). And this impact was amplified in obese patients (OR: 2.51, 95%CI: 1.95-3.06, P<0.05). Conclusion: Our results confirmed that controls on weight and blood pressure might be candidate therapeutic strategy for GSD prevention. And concerns should be raised on de-novo NAFLD after cholecystectomy.

Application of bioreactor technology for cell culture-based viral vaccine production: Present status and future prospects.

Bioreactors are widely used in cell culture-based viral vaccine production, especially during the coronavirus disease 2019 (COVID-19) pandemic. In this context, the development and application of bioreactors can provide more efficient and cost-effective vaccine production to meet the global vaccine demand. The production of viral vaccines is inseparable from the development of upstream biological processes. In particular, exploration at the laboratory-scale is urgently required for further development. Therefore, it is necessary to evaluate the existing upstream biological processes, to enable the selection of pilot-scale conditions for academic and industrial scientists to maximize the yield and quality of vaccine development and production. Reviewing methods for optimizing the upstream process of virus vaccine production, this review discusses the bioreactor concepts, significant parameters and operational strategies related to large-scale amplification of virus. On this basis, a comprehensive analysis and evaluation of the various process optimization methods for the production of various viruses (SARS-CoV-2, Influenza virus, Tropical virus, Enterovirus, Rabies virus) in bioreactors is presented. Meanwhile, the types of viral vaccines are briefly introduced, and the established animal cell lines for vaccine production are described. In addition, it is emphasized that the co-development of bioreactor and computational biology is urgently needed to meet the challenges posed by the differences in upstream production scales between the laboratory and industry.

An updated review of SARS-CoV-2 detection methods in the context of a novel coronavirus pandemic.

The World Health Organization has reported approximately 430 million confirmed cases of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), worldwide, including nearly 6 million deaths, since its initial appearance in China in 2019. While the number of diagnosed cases continues to increase, the need for technologies that can accurately and rapidly detect SARS-CoV-2 virus infection at early phases continues to grow, and the Federal Drug Administration (FDA) has licensed emergency use authorizations (EUAs) for virtually hundreds of diagnostic tests based on nucleic acid molecules and antigen-antibody serology assays. Among them, the quantitative real-time reverse transcription PCR (qRT-PCR) assay is considered the gold standard for early phase virus detection. Unfortunately, qRT-PCR still suffers from disadvantages such as the complex test process and the occurrence of false negatives; therefore, new nucleic acid detection devices and serological testing technologies are being developed. However, because of the emergence of strongly infectious mutants of the new coronavirus, such as Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (B.1.1.529), the need for the specific detection of mutant strains is also increasing. Therefore, this article reviews nucleic acid- and antigen-antibody-based serological assays, and compares the performance of some of the most recent FDA-approved and literature-reported assays and associated kits for the specific testing of new coronavirus variants.

Analysis of the Protective Efficacy of Approved COVID-19 Vaccines Against Various Mutants.

The outbreak of COVID-19 (caused by SARS-CoV-2) has posed a significant threat to global public health security because of its high pathogenicity and infectivity. To date, the pathogenic mechanism of this novel coronavirus (SARS-CoV-2) is still unclear, and there is no effective treatment. As one of the most effective strategies to prevent viral infection, vaccines have become a research hotspot. Based on the current understanding of SARS-CoV-2, the research and development of its vaccines cover almost all forms of current vaccine research, including inactivated vaccines, recombinant protein vaccines, viral vector vaccines, and nucleic acid vaccines. Moreover, with the spread of the new mutant virus, it is necessary to evaluate the protection rate of previous administered vaccines. This article reviews the candidate targets, vaccine types, research and development status, progress of SARS-CoV-2 vaccines, and the effectiveness of neutralizing antibodies against SARS-CoV-2 mutants (B.1.1.7, B.1.351, P.1, B.1.617.2, and B.1.1.529) induced by these vaccines, to provide a reference for follow-up research and prevention.