Salivary Blockade Protects the Lower Respiratory Tract of Mice from Lethal Influenza Virus Infection.

It is possible to model the progression of influenza virus from the upper respiratory tract to the lower respiratory tract in the mouse using viral inoculum delivered in a restricted manner to the nose. In this model, infection with the A/Udorn/307/72 (Udorn) strain of virus results ultimately in high viral titers in both the trachea and lungs. In contrast, the A/Puerto Rico/8/34 (PR8) strain causes an infection that is almost entirely limited to the nasal passages.

Synthetic B-Cell Epitopes Eliciting Cross-Neutralizing Antibodies: Strategies for Future Dengue Vaccine.

Dengue virus (DENV) is a major public health threat worldwide. A key element in protection from dengue fever is the neutralising antibody response. Anti-dengue IgG purified from DENV-2 infected human sera showed reactivity against several peptides when evaluated by ELISA and epitope extraction techniques.

Enterovirus-Specific Anti-peptide Antibodies.

Enterovirus 71 (EV-71) is the main causative agent of hand, foot, and mouth disease (HFMD) which is generally regarded as a mild childhood disease. In recent years, EV71 has emerged as a significant pathogen capable of causing high mortalities and severe neurological complications in large outbreaks in Asia. A formalin-inactivated EV71 whole virus vaccine has completed phase III trial in China but is currently unavailable clinically.

Initial evidence on differences among Enterovirus 71, Coxsackievirus A16 and Coxsackievirus B4 in binding to cell surface heparan sulphate.

Cell surface heparan sulphate (HS) mediates infection for many viruses from diverse families. We demonstrated significant antiviral potencies for a number of HS mimetics against a cloned strain of Enterovirus 71 (EV71) in a previous study. Thus, the involvement of HS in mediating viral infection of isolates of human enteroviruses was investigated in Vero and human neural cells in the present work.

Development of antiviral agents toward enterovirus 71 infection.

Enterovirus 71 (EV71) infection remains a public health problem at a global level, particularly in the Asia-Pacific region. The infection normally manifests as hand-foot-mouth disease; however, it is capable of developing into potentially fatal neurological complications. There is currently no approved vaccine or antiviral substance available for the prevention or treatment of EV71 infection.

Identification of traditional medicinal plant extracts with novel anti-influenza activity.

The emergence of drug resistant variants of the influenza virus has led to a need to identify novel and effective antiviral agents. As an alternative to synthetic drugs, the consolidation of empirical knowledge with ethnopharmacological evidence of medicinal plants offers a novel platform for the development of antiviral drugs. The aim of this study was to identify plant extracts with proven activity against the influenza virus.

A colorimetric-based accurate method for the determination of enterovirus 71 titer.

The 50 % tissue culture infectious dose (TCID50) is still one of the most commonly used techniques for estimating virus titers. However, the traditional TCID50 assay is time consuming, susceptible to subjective errors and generates only quantal data. Here, we describe a colorimetric-based approach for the titration of Enterovirus 71 (EV71) using a modified method for making virus dilutions.

Global impact of heparin on gene expression profiles in neural cells infected by enterovirus 71.

Objectives: Heparan sulphate mimetics, particularly heparin (Hep), have previously been shown to considerably inhibit infection of enterovirus 71 (EV71) in Vero cells. Therefore, in this study, a genome-wide DNA microarray was performed to gain insight into the mechanism(s) of action of Hep against infection of a human neural cell line, SK-N-SH, with a clinical strain of EV71.

Methods: This study focused on a selection of EV71-induced genes whose expression profiling was exclusively affected by the antiviral activity of Hep.

In vitro evaluation of the antiviral activity of heparan sulfate mimetic compounds against Enterovirus 71.

Enterovirus 71 (EV71) is the causative agent of hand foot and mouth disease (HFMD) and can also cause fatal neurological complications for which currently there is no vaccine or approved antiviral drug. Despite suggestions that heparan sulfate (HS)-like compounds are effective antivirals against various viruses, no research has been undertaken to examine their effects upon EV71. Therefore, this study aimed to investigate the in vitro anti-EV71 effect of HS mimetics (heparin, heparan sulfate, and pentosan polysulfate).

Structural requirement for the agonist activity of the TLR2 ligand Pam2Cys.

Synthetic lipopeptides have demonstrated great potential as a vaccine strategy for eliciting cellular and humoral immunity. One of the most potent lipid moieties used is S-[2,3-bis(palmitoyloxy)propyl]cysteine (Pam2Cys). Pam2Cys binds to and activates dendritic cells by engagement of Toll like receptor 2 (TLR 2).

A self-adjuvanting multiepitope immunogen that induces a broadly cross-reactive antibody to hepatitis C virus.

Unlabelled: We describe a peptide-based strategy for HCV vaccine design that addresses the problem of variability in hypervariable region 1 (HVR1). Peptides representing antibody epitopes of HVR1 from genotype 1a were synthesized and incorporated into multideterminant immunogens that also included lipid moieties and helper T (T(h)) cell epitopes. Mice inoculated with these polyepitopes generated strong antibody responses.

Exploiting information inherent in binding sites of virus-specific antibodies: design of an HCV vaccine candidate cross-reactive with multiple genotypes.

Background/aims: The role of antibody in hepatitis C virus (HCV) infection remains unclear although many reports attest to its role in viral clearance. Here we describe epitopes that are recognized by antibody present in the serum of infected patients and show that such epitopes can induce neutralizing antibodies.

Methods: Human serum containing hyperimmune anti-HCV IgG was used to extract epitopes from a library of synthetic peptides that encompassed the sequences of the E1 and E2 proteins of HCV genotype 1a H77.

Induction of neutralizing antibody responses to hepatitis C virus with synthetic peptide constructs incorporating both antibody and T-helper epitopes.

We describe a peptide-based strategy for hepatitis C virus (HCV) vaccine design that exploits synthetic peptides representing antibody epitopes of the hypervariable region 1 (HVR1) of the E2 glycoprotein and also less variable regions immediately downstream of HVR1. These epitopes were linked to a T-helper (T(h)) epitope (KLIPNASLIENCTKAEL) derived from the Morbillivirus canine distemper virus. Antibody titres induced by the two vaccine candidates T(h)-A (E2 amino acid 384-414) and T(h)-B (E2 amino acid 390-414) were significantly higher than those produced against vaccines lacking the T(h) epitope (P<0.