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An Improved and High Throughput Respiratory Syncytial Virus (RSV) Micro-neutralization Assay

Respiratory syncytial virus-specific neutralizing antibodies (RSV NAbs) are an important marker of protection against RSV. A number of different assay ...

University of Queensland

Acute respiratory infection (ARI) is an important cause of morbidity in children. Mixed aetiology is frequent, with pathogenic viruses and bacteria co-detected in respiratory secretions. However, the clinical significance of these viral/bacterial co-infections has long been a controversial topic. While severe bacterial pneumonia following influenza infection has been well described, associations are less clear among infections caused by viruses that are more common in young children, such as respiratory syncytial virus. Although assessing the overall contribution of bacteria to disease severity is complicated by the presence of many confounding factors in clinical studies, understanding the role of viral/bacterial co-infections in defining the outcome of paediatric ARI will potentially reveal novel treatment and prevention strategies, improving patient outcomes. This review summarizes current evidence for the clinical significance of respiratory viral/bacterial co-infections in young children, discusses possible mechanisms of cooperative interaction between these pathogens and highlights areas that require further investigation.

Viral bacterial co-infection of the respiratory tract during early childhood.

Koala populations are in serious decline across many areas of mainland Australia, with infectious disease a contributing factor. Koala retrovirus (KoRV) is a gammaretrovirus present in most wild koala populations and captive colonies. Five subtypes of KoRV (A to E) have been identified based on amino acid sequence divergence in a hypervariable region of the receptor binding domain of the envelope protein. However, analysis of viral genetic diversity has been conducted primarily on KoRV in captive koalas housed in zoos in Japan, the United States, and Germany. Wild koalas within Australia have not been comparably assessed. Here we report a detailed analysis of KoRV genetic diversity in samples collected from 18 wild koalas from southeast Queensland. By employing deep sequencing we identified 108 novel KoRV envelope sequences and determined their phylogenetic diversity. Genetic diversity in KoRV was abundant and fell into three major groups; two comprised the previously identified subtypes A and B, while the third contained the remaining hypervariable region subtypes (C, D, and E) as well as four hypervariable region subtypes that we newly define here (F, G, H, and I). In addition to the ubiquitous presence of KoRV-A, which may represent an exclusively endogenous variant, subtypes B, D, and F were found to be at high prevalence, while subtypes G, H, and I were present in a smaller number of animals.

Phylogenetic Diversity of Koala Retrovirus within a Wild Koala Population.

Respiratory syncytial virus (RSV) causes severe lower respiratory tract illness in infants and young children. The significant morbidity and mortality rates associated with RSV infection make an effective RSV vaccine development a priority. Two neutralising antibody binding sites, Ø and II, located on the pre-fusion RSV F glycoprotein are prime candidates for epitope-focused vaccine design. We report on a vaccine strategy that utilises a lipid core peptide (LCP) delivery system with self-adjuvanting properties in conjunction with either the antigenic site Ø or II (B cell epitopes) along with PADRE as a T helper cell epitope. These LCP constructs adopted the desired helical conformation in solution and were recognised by their cognate antibodies D25 and Motavizumab, specific for site Ø and II on RSV F protein, respectively. The LCP constructs were capable of eliciting higher levels of antigen specific antibodies than those induced by antigens administered with complete Freund's adjuvant, demonstrating the potent adjuvanting properties of LCP delivery. However, the antibodies induced failed to recognise native F protein or neutralise virus infectivity. These results provide a note of caution in assuming that peptide vaccines, successfully designed to structurally mimic minimal linear B cell epitopes, will necessarily elicit the desired immune response.

Induction of high titred, non-neutralising antibodies by self-adjuvanting peptide epitopes derived from the respiratory syncytial virus fusion protein.

Keith Chappell

School of Chemistry and Molecular Bioscience

University of Queensland

An Improved and High Throughput Respiratory Syncytial Virus (RSV) Micro-neutralization Assay

Keith Chappell

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}School of Chemistry and Molecular Bioscience

University of Queensland

An Improved and High Throughput Respiratory Syncytial Virus (RSV) Micro-neutralization Assay

School of Chemistry and Molecular Bioscience