Production of antigenically stable enterovirus A71 virus-like particles in as a vaccine candidate.

Enterovirus A71 (EVA71) causes widespread disease in young children with occasional fatal consequences. In common with other picornaviruses, both empty capsids (ECs) and infectious virions are produced during the viral lifecycle. While initially antigenically indistinguishable from virions, ECs readily convert to an expanded conformation at moderate temperatures.

Production of antigenically stable enterovirus A71 virus-like particles in as a vaccine candidate.

Enterovirus A71 (EVA71) causes widespread disease in young children with occasional fatal consequences. In common with other picornaviruses, both empty capsids (ECs) and infectious virions are produced during the viral lifecycle. While initially antigenically indistinguishable from virions, ECs readily convert to an expanded conformation at moderate temperatures.

Sustained detection of type 2 poliovirus in London sewage between February and July, 2022, by enhanced environmental surveillance.

Background: The international spread of poliovirus exposes all countries to the risk of outbreaks and is designated a Public Health Emergency of International Concern by WHO. This risk can be exacerbated in countries using inactivated polio vaccine, which offers excellent protection against paralysis but is less effective than oral vaccine against poliovirus shedding, potentially allowing circulation without detection of paralytic cases for long periods of time. Our study investigated the molecular properties of type 2 poliovirus isolates found in sewage with an aim to detect virus transmission in the community.

Cross-Antigenicity between EV71 Sub-Genotypes: Implications for Vaccine Efficacy.

Enterovirus A-71 (EV71) is a global, highly contagkkious pathogen responsible for severe cases of hand-food-mouth-disease (HFMD). The use of vaccines eliciting cross neutralizing antibodies (NTAbs) against the different circulating EV71 sub-genotypes is important for preventing HFMD outbreaks. Here, we tested the cross-neutralizing activities induced by EV71 genotype/sub-genotype A, B0-B4, C1, C2, C4, and C5 viruses using rats.

Differences in Antigenic Structure of Inactivated Polio Vaccines Made From Sabin Live-Attenuated and Wild-Type Poliovirus Strains: Impact on Vaccine Potency Assays.

Background: Following the declaration of wild-type 2 poliovirus eradication in 2015, the type 2 component was removed from the live-attenuated oral polio vaccine (OPV). This change implies a need to improve global coverage through routine immunization with inactivated polio vaccine (IPV), to ensure type 2 immunity. Several manufacturers use Sabin OPV strains for IPV production (sIPV), rather than the usual wild-type strains used for conventional IPV (cIPV).

Oncolytic Group B Adenovirus Enadenotucirev Mediates Non-apoptotic Cell Death with Membrane Disruption and Release of Inflammatory Mediators.

Enadenotucirev (EnAd) is a chimeric group B adenovirus isolated by bioselection from a library of adenovirus serotypes. It replicates selectively in and kills a diverse range of carcinoma cells, shows effective anticancer activity in preclinical systems, and is currently undergoing phase I/II clinical trials. EnAd kills cells more quickly than type 5 adenovirus, and speed of cytotoxicity is dose dependent.

Actin-resistant DNAse I Expression From Oncolytic Adenovirus Enadenotucirev Enhances Its Intratumoral Spread and Reduces Tumor Growth.

Spread of oncolytic viruses through tumor tissue is essential to effective virotherapy. Interstitial matrix is thought to be a significant barrier to virus particle convection between "islands" of tumor cells. One way to address this is to encode matrix-degrading enzymes within oncolytic viruses, for secretion from infected cells.

Improved in vitro human tumor models for cancer gene therapy.

Developing effective anticancer treatments is a particular challenge, as agents must contend with not only the target cellular biology, but also with the complex tumor microenvironment. Here we discuss various in vitro strategies that have sought to address this issue, with a particular focus on new methodologies that utilize clinical samples in basic research and their application in gene therapy and virotherapy.

Tissue-specific attenuation of oncolytic sindbis virus without compromised genetic stability.

Wild-type Sindbis virus (SV) shows promise as an oncolytic agent, although potential off-target replication is a safety concern. To remove possible pathology reflecting virus replication in liver, muscle, and/or hematopoietic cells, microRNA (miR)-response elements (MREs) to liver-specific miR122, muscle-specific miR133a and miR206, or hematopoietic-specific miR142-3p were inserted into the Sindbis viral genome. We compared the effectiveness of MREs in two distinct genomic locations and found better tissue-specific attenuation when they were inserted into the structural polyprotein coding region (up to 6000-fold selectivity with miR142-3p) rather than into the 3' untranslated region (up to 850-fold with miR142-3p).

Immunogenicity in mice of human metapneumovirus with a truncated SH glycoprotein.

The SH glycoprotein of human metapneumovirus (HMPV) is twice the size of that of human respiratory syncytial virus and possesses a large, hydrophilic luminal domain. The glycoprotein is located on the surface of the virion and of virus infected cells and, if immunogenic, might be expected to play a role in anti-viral immunity. Initial attempts to study anti-SH antibody immunogenicity were thwarted by the instability of the SH gene on passage both in human bronchial epithelial cells and in mice.

The characterization of monoclonal antibodies to human metapneumovirus and the detection of multiple forms of the virus nucleoprotein and phosphoprotein.

Little is known of the proteome of human metapneumovirus (HMPV). In this study a panel of monoclonal antibodies to the virus have been characterized and used to identify viral proteins present in infected cell lysates. Of thirteen anti-HMPV monoclonal antibodies four reacted with recombinant fusion glycoprotein and one with recombinant G glycoprotein by immunofuorescence but not in western blots suggesting that they recognize conformation dependent epitopes.

Virotherapy--cancer targeted pharmacology.

Building on their success in vaccination, many groups are now exploring the use of viruses as anticancer agents. In general, viral therapeutics provide the possibility to express anticancer proteins directly at the tumour site, decreasing exposure to normal tissue during delivery and maximising therapeutic index. Some viruses are also 'oncolytic', either naturally or by design, and these agents function to kill cancer cells selectively before spreading to infect adjacent cells and repeat the process.