Intranasal influenza-vectored COVID-19 vaccines confer broad protection against SARS-CoV-2 XBB variants in hamsters.

The XBB.1.5 subvariant has garnered significant attention due to its exceptional immune evasion and transmissibility.

Immunogenicity and safety of an ORF7-deficient skin-attenuated and neuro-attenuated live vaccine for varicella: a randomised, double-blind, controlled, phase 2a trial.

Background: The Oka varicella vaccine strain remains neurovirulent and can establish lifelong latent infection, raising safety concerns about vaccine-related herpes zoster. In this study, we aimed to evaluate the immunogenicity and safety of a skin-attenuated and neuro-attenuated varicella vaccine candidate (v7D vaccine).

Methods: We did this randomised, double-blind, controlled, phase 2a clinical trial in Jiangsu, China.

Safety and efficacy of the intranasal spray SARS-CoV-2 vaccine dNS1-RBD: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

Background: The live-attenuated influenza virus vector-based intranasal SARS-CoV-2 vaccine (dNS1-RBD, Pneucolin; Beijing Wantai Biological Pharmacy Enterprise, Beijing, China) confers long-lasting and broad protection in animal models and is, to our knowledge, the first COVID-19 mucosal vaccine to enter into human trials, but its efficacy is still unknown. We aimed to assess the safety and efficacy (but not the immunogenicity) of dNS1-RBD against COVID-19.

Methods: We did a multicentre, randomised, double-blind, placebo-controlled, adaptive design, phase 3 trial at 33 centres (private or public hospitals, clinical research centres, or Centre for Disease Control and Prevention) in four countries (Colombia, Philippines, South Africa, and Viet Nam).

Parvovirus B19 DNA and antibodies in Chinese plasma donors, plasma pools and plasma derivatives.

Background: Human parvovirus B19 (B19V) is a common contaminant found in plasma pools and plasma derivatives. Previous studies were mainly focused on limited aspects, further assessment of prevalence of B19V DNA and antibodies in plasma donors, the contamination of B19V in pooled plasma and plasma derivatives should be performed in China.

Study Design And Methods: Individual plasma donors' samples from four provinces and pooled plasma from four Chinese blood product manufacturers were collected and screened using B19V DNA diagnostic kits between October 2018 and May 2020.

Safety and immunogenicity of a skin- and neuro-attenuated live vaccine for varicella: a randomized, double-blind, controlled, dose-escalation and age de-escalation phase 1 clinical trial.

Background: Despite the success in decreasing varicella-related disease burden, live-attenuated Oka vaccine strain of varicella-zoster virus (vOka) remains neuro-virulence and may establish latency and reactivate, raising safety concerns. Here we aimed to evaluate the safety and immunogenicity of a skin- and neuro-attenuated varicella vaccine candidate (v7D).

Methods: This is a randomized, double-blind, placebo-controlled, dose-escalation and age de-escalation phase 1 clinical trial conducted in Liuzhou, China (ChiCTR1900022284).

A microfluidic system for rapid nucleic acid analysis based on real-time convective PCR at point-of-care testing.

A microfluidic system for rapid nucleic acid analysis based on real-time convective PCR is developed. To perform 'sample-in, answer-out' nucleic acid analysis, a microfluidic chip is developed to efficiently extract nucleic acid, and meanwhile convective PCR (CPCR) is applied for rapid nucleic acid amplification. With an integrated microfluidic chip consisting of reagent pre-storage chambers, a lysis & wash chamber, an elution chamber and a waste chamber, nucleic acid extraction based on magnetic beads can be automatically performed for a large size of test sample within a limited time.

Oncolytic virus expressing PD-1 inhibitors activates a collaborative intratumoral immune response to control tumor and synergizes with CTLA-4 or TIM-3 blockade.

Background: Oncolytic viruses (OVs) are capable to inflame the tumor microenvironment (TME) and elicit infiltrating tumor-specific T cell responses. However, OV treatment negatively alters the cancer-immune set point in tumors to attenuate the antitumor immune response, which suggests the necessity of dissecting the immune landscape of the virus-treated tumors and developing novel strategies to maximize the potential of OVs. The aim of this study is to investigate the effect of the single-chain variable fragment (scFv)-armed OVs targeting PD-1 on the TME, and ultimately overcome localized immunosuppression to sensitize tumors to immunotherapies.

Safety and immunogenicity of a live-attenuated influenza virus vector-based intranasal SARS-CoV-2 vaccine in adults: randomised, double-blind, placebo-controlled, phase 1 and 2 trials.

Background: All currently available SARS-CoV-2 vaccines are administered by intramuscular injection. We aimed to evaluate the safety and immunogenicity of a live-attenuated influenza virus vector-based SARS-CoV-2 vaccine (dNS1-RBD) administered by intranasal spray in healthy adults.

Methods: We did double-blind, randomised, placebo-controlled phase 1 and 2 trials, followed by a phase 2 extension trial, at a single centre in Jiangsu, China.

A live attenuated virus-based intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2.

Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 d after single-dose vaccination or 9 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight.

Development of a skin- and neuro-attenuated live vaccine for varicella.

Varicella caused by the primary infection of varicella-zoster virus (VZV) exerts a considerable disease burden globally. Current varicella vaccines consisting of the live-attenuated vOka strain of VZV are generally safe and effective. However, vOka retains full neurovirulence and can establish latency and reactivate to cause herpes zoster in vaccine recipients, raising safety concerns.

Cryo-EM structures reveal the molecular basis of receptor-initiated coxsackievirus uncoating.

Enterovirus uncoating receptors bind at the surface depression ("canyon") that encircles each capsid vertex causing the release of a host-derived lipid called "pocket factor" that is buried in a hydrophobic pocket formed by the major viral capsid protein, VP1. Coxsackievirus and adenovirus receptor (CAR) is a universal uncoating receptor of group B coxsackieviruses (CVB). Here, we present five high-resolution cryoEM structures of CVB representing different stages of virus infection.

Recombinant SARS-CoV-2 RBD with a built in T helper epitope induces strong neutralization antibody response.

Without approved vaccines and specific treatments, COVID-19 is spreading around the world with above 26 million cases and approximately 864 thousand deaths until now. An efficacious and affordable vaccine is urgently needed. The Val308 - Gly548 of spike protein of SARS-CoV-2 linked with Gln830 - Glu843 of Tetanus toxoid (TT peptide) (designated as S1-4) and without TT peptide (designated as S1-5) were expressed and renatured.

Near-atomic cryo-electron microscopy structures of varicella-zoster virus capsids.

Varicella-zoster virus (VZV) is a medically important human herpesvirus that causes chickenpox and shingles, but its cell-associated nature has hindered structure studies. Here we report the cryo-electron microscopy structures of purified VZV A-capsid and C-capsid, as well as of the DNA-containing capsid inside the virion. Atomic models derived from these structures show that, despite enclosing a genome that is substantially smaller than those of other human herpesviruses, VZV has a similarly sized capsid, consisting of 955 major capsid protein (MCP), 900 small capsid protein (SCP), 640 triplex dimer (Tri2) and 320 triplex monomer (Tri1) subunits.

A uniform quantitative enzyme-linked immunosorbent assay for Coxsackievirus A16 antigen in vaccine.

Coxsackievirus A16 (CV-A16), one of major etiological agents of hand, foot and mouth disease (HFMD), causes outbreaks of the disease in young children all over the world. In order to promote the prevention and control of HFMD, the research and development of CV-A16 vaccine have been carried out in China. However, due to lacking of a recognized CV-A16 antigen detection method, the evaluation and quality control (QC) of vaccine effectiveness are greatly limited.

Identification of Antibodies with Non-overlapping Neutralization Sites that Target Coxsackievirus A16.

Hand, foot, and mouth disease is a common childhood illness primarily caused by coxsackievirus A16 (CVA16), for which there are no current vaccines or treatments. We identify three CVA16-specific neutralizing monoclonal antibodies (nAbs) with therapeutic potential: 18A7, 14B10, and NA9D7. We present atomic structures of these nAbs bound to all three viral particle forms-the mature virion, A-particle, and empty particle-and show that each Fab can simultaneously occupy the mature virion.

Serological survey of neutralizing antibodies to eight major enteroviruses among healthy population.

Human enteroviruses (EVs) are the most common causative agents infecting human, causing many harmful diseases, such as hand, foot, and mouth disease (HFMD), herpangina (HA), myocarditis, encephalitis, and aseptic meningitis. EV-related diseases pose a serious worldwide threat to public health. To gain comprehensive insight into the seroepidemiology of major prevalent EVs in humans, we firstly performed a serological survey for neutralizing antibodies (nAbs) against Enterovirus A71 (EV-A71), Coxsackie virus A16 (CV-A16), Coxsackie virus A6 (CV-A6), Coxsackie virus A10 (CV-A10), Coxsackie virus B3 (CV-B3), Coxsackie virus B5 (CV-B5), Echovirus 25 (ECHO25), and Echovirus 30 (ECHO30) among the healthy population in Xiamen City in 2016, using micro-neutralization assay.

Atomic structures of Coxsackievirus A6 and its complex with a neutralizing antibody.

Coxsackievirus A6 (CVA6) has recently emerged as a major cause of hand, foot and mouth disease in children worldwide but no vaccine is available against CVA6 infections. Here, we demonstrate the isolation of two forms of stable CVA6 particles-procapsid and A-particle-with excellent biochemical stability and natural antigenicity to serve as vaccine candidates. Despite the presence (in A-particle) or absence (in procapsid) of capsid-RNA interactions, the two CVA6 particles have essentially identical atomic capsid structures resembling the uncoating intermediates of other enteroviruses.

A novel method of multiple nucleic acid detection: Real-time RT-PCR coupled with probe-melting curve analysis.

A novel method, real-time reverse transcription PCR (real-time RT-PCR) coupled with probe-melting curve analysis, has been established to detect two kinds of samples within one fluorescence channel. Besides a conventional TaqMan probe, this method employs another specially designed melting-probe with a 5' terminus modification which meets the same label with the same fluorescent group. By using an asymmetric PCR method, the melting-probe is able to detect an extra sample in the melting stage effectively while it almost has little influence on the amplification detection.

Characterization and analysis of real-time capillary convective PCR toward commercialization.

Almost all the reported capillary convective polymerase chain reaction (CCPCR) systems to date are still limited to research use stemming from unresolved issues related to repeatability, reliability, convenience, and sensitivity. To move CCPCR technology forward toward commercialization, a couple of critical strategies and innovations are discussed here. First, single- and dual-end heating strategies are analyzed and compared between each other.

A neonatal mouse model of coxsackievirus A10 infection for anti-viral evaluation.

Epidemiological data indicate that coxsackievirus A10 (CVA10) has become one of the main causative agents of hand, foot and mouth disease (HFMD) and in recent years has often been found to co-circulate with other enteroviruses, which poses a challenge for the prevention and control of HFMD. Although most CVA10-associated HFMD cases present mild symptoms, severe manifestations and even death can also occur. However, the study of the pathogenesis and the development of drugs and vaccines for CVA10 infection are still far from complete.

Evaluation of immunity to varicella zoster virus with a novel double antigen sandwich enzyme-linked immunosorbent assay.

Varicella is a highly contagious disease caused by primary infection of Varicella zoster virus (VZV). Varicella can be severe or even lethal in susceptible adults, immunocompromised patients and neonates. Determination of the status of immunity to VZV is recommended for these high-risk populations.

A neonatal mouse model for the evaluation of antibodies and vaccines against coxsackievirus A6.

Coxsackievirus A6 (CA6) can induce atypical hand, foot, and mouth disease, which is characterized by severe rash, onychomadesis and a higher rate of infection in adults. Increasing epidemiological data indicated that outbreaks of CA6-associated hand, foot, and mouth disease have markedly increased worldwide in recent years. However, the current body of knowledge on the infection, pathogenic mechanism, and immunogenicity of CA6 is still very limited.

A Low-Cost and Fast Real-Time PCR System Based on Capillary Convection.

A low-cost and fast real-time PCR system in a pseudo-isothermal manner with disposable capillary tubes based on thermal convection for point-of-care diagnostics is developed and tested. Once stable temperature gradient along the capillary tube has been established, a continuous circulatory flow or thermal convection inside the capillary tube will repeatedly transport PCR reagents through temperature zones associated with the DNA denaturing, annealing, and extension stages of the reaction. To establish stable temperature gradient along the capillary tube, a dual-temperature heating strategy with top and bottom heaters is adopted here.

A highly conserved epitope-vaccine candidate against varicella-zoster virus induces neutralizing antibodies in mice.

Varicella-zoster virus (VZV) is a highly infectious agent of varicella and herpes zoster (HZ). Vaccination is by far the most effective way to prevent these diseases. More safe, stable and efficient vaccines, such as epitope-based vaccines, now have been increasingly investigated by many researchers.