The potential for production of freeze-dried oral vaccines using alginate hydrogel microspheres as protein carriers

Oral administration of dry vaccine formulations is acknowledged to offer major clinical and logistical benefits by eliminating the cold chain required for liquid preparations. A model antigen, bovine serum albumin (BSA) was encapsulated in alginate microspheres using aerosolisation. Hydrated microspheres 25 to 65 μm in size with protein loading of 3.3 % w/w were obtained. Environmental scanning electron microscopy indicated a stabilizing effect of encapsulated protein on alginate hydrogels revealed by an increase in dehydration resistance. Freeze drying of alginate microspheres without use of a cryoprotectant resulted in fragmentation and subsequent rapid loss of the majority of the protein load in simulated intestinal fluid in 2 h, whereas intact microspheres were observed following freeze-drying of BSA-loaded microspheres in the presence of maltodextrin. BSA release from freeze-dried preparations was limited to less than 7 % in simulated gastric fluid over 2 h, while 90 % of the protein load was gradually released in simulated intestinal fluid over 10 h. SDS-PAGE analysis indicated that released BSA largely preserved its molecular weight. These findings demonstrate the potential for manufacturing freeze-dried oral vaccines using alginate microspheres.

The vaccination-challenge trial: the gold standard test to evaluate the protective efficacy of infectious coryza vaccines

Infectious coryza is an upper respiratory tract disease of chickens with the major impact occurring in multi-age flocks. We investigated the relationship between the level of antibodies, as detected by a haemagglutination-inhibition (HI) assay, in infectious coryza-vaccinated chickens and the protection against challenge in those chickens. In one experiment, chickens given a single dose of either of two infectious coryza vaccines lacked a detectable HI response to vaccination but showed significant levels of protection 11 weeks after vaccination. In contrast, in chickens given two doses of an infectious coryza vaccine and challenged 3 weeks after the second vaccine dose, there was a strong serological response with 36/40 birds having a HI titre of 1/20 or greater. In this trial there was an apparent relationship between titre and subsequent protection, with none of the 32 chickens with a titre of 1/40 or 1/80 showing any clinical signs and only one of the same group yielding the challenge organism on culture. In contrast, three of the four vaccinated chickens with a HI titre less than 1/5 developed the typical clinical signs of coryza and yielded the challenge organism on culture. Overall, our results suggest that HI titres cannot be regarded as a definitive predictor of vaccine efficacy. We suggest that the vaccination-challenge trial is the gold standard for the evaluation of the immune response to infectious coryza vaccines.

Equine influenza in Australia

Letter to the editor.

Australia’s first Pharmacists Immunisation Pilot – about the service

Background: The first phase of the Queensland Pharmacist Immunisation Pilot (QPIP) ran between April and August 2014, to pilot pharmacists administering influenza vaccinations for the flu season for the first time in Australia. Aim: An aim was to investigate factors facilitating implementation of a pharmacist vaccination service in the community pharmacy setting. Method: The QPIP pharmacies were divided into two arms; the South East Queensland arm consisting of 51 Terry White Chemists (TWCs), and 29 pharmacies in the North Queensland (NQ) arm. The TWCs featured pharmacies which previously provided a vaccination service and that were experienced with using an online booking system, providing an opportunity to capture booking data. Results: The TWCs delivered 9902 (90%) of the influenza vaccinations in QPIP. Of these, 48.5% of the vaccines were delivered via appointments made using the online booking system, while 13.3% were in-store bookings. Over one-third (38.2%) of the vaccinations delivered in were “walk-ins” where the vaccination was delivered ‘on the spot’ as spontaneous or opportunistic vaccinations. The absence of a booking system meant all vaccinations delivered in the NQ arm were “walk-ins”. The online-booking data showed 10:00 am and Tuesday being the most popular time and day for vaccinations. Patients preferred having their vaccinations in private consultation rooms, over areas which used a screen to partition off a private area. Discussion: The presence of an online booking system appeared to increase the efficiency and penetration of the of vaccine service delivery. Also, as the level of privacy afforded to patients increased, the number of patients vaccinated also increased. Conclusions: As pharmacist-delivered vaccination services start to progressively roll out across Australia; these findings pave the way for more efficient and effective implementation of the service.

Positive results in a real-time PCR for type A influenza associated with the use of an inactivated vaccine.

A real-time reverse transcription polymerase chain reaction (qRT-PCR) test for the matrix gene of type A influenza viruses was used during the 2007 Australian equine influenza (EI) outbreak in order to confirm diagnosis and, later, eradication of the virus. During the EI outbreak, horses being exported required vaccination and individual proof of freedom from EI. At the end of the outbreak, positive results were obtained from four horses destined for export, because of contamination of the samples with the vaccine. This report highlights the need for EI testing and vaccination to occur on separate days and with the collection of swabs for testing to precede vaccination.

The first five days: field and laboratory investigations during the early stages of the equine influenza outbreak in Australia, 2007.

Until August 2007, Australia was one of only three countries internationally recognised to be free of equine influenza (EI). This report documents the diagnosis of the first cases of EI in Australian horses and summarises the investigations that took place over the next 5 days. During that time, a multifocal outbreak was identified across eastern New South Wales and south-eastern Queensland. The use of an influenza type A pan-reactive real-time reverse transcription polymerase chain reaction allowed rapid confirmation of suspect cases of EI.

The August 2007 equine influenza response management framework.

This section outlines the most important issues addressed in the management of the response in the two infected states, New South Wales and Queensland. There were differences in the management of the response between the states for logistic, geographic and organisation structural reasons. Issues included the use of control centres, information centres, the problems associated with the lack of trained staff to undertake all the roles, legislative issues, controls of horse movements, the availability of resources for adequate surveillance, the challenges of communication between disparate groups and tracing the movements of both humans and horses.

High-level coordination and strategy in the 2007 equine influenza outbreak response.

The equine influenza (EI) outbreak presented many challenges that required high-level coordination and decision making, as well as the development of new approaches for satisfactory and consistent resolution. This paper outlines the elements of the national coordination arrangements, preparatory arrangements in place prior to the outbreak that facilitated national coordination, and some of the issues faced and resolved in the response.

Significant features of the epidemiology of equine influenza in Queensland, Australia, 2007.

An outbreak of equine influenza (EI) caused by influenza A H3N8 subtype virus occurred in the Australian states of Queensland and New South Wales in August 2007. Infection in the Australian horse population was associated with the introduction of infection by horses from overseas. The first case of EI in Queensland was detected on 25 August 2007 at an equestrian sporting event. Infection subsequently spread locally and to other clusters through horse movements prior to the implementation of an official standstill. There were five main clusters of infected properties during this outbreak and several outliers, which were investigated to find the potential mechanism of disease spread. To contain the outbreak, Queensland was divided into infection status zones, with different movement controls applied to each zone. Vaccination was implemented strategically in infected areas and within horse subpopulations. Control and eventual eradication of EI from Queensland was achieved through a combination of quarantine, biosecurity measures, movement control, rapid diagnostic testing and vaccination.

Risk-based surveillance for avian influenza control along poultry market chains in South China: The value of social network analysis.

Over the past two decades, the poultry sector in China went through a phase of tremendous growth as well as rapid intensification and concentration. Highly pathogenic avian influenza virus (HPAIV) subtype H5N1 was first detected in 1996 in Guangdong province, South China and started spreading throughout Asia in early 2004. Since then, control of the disease in China has relied heavily on wide-scale preventive vaccination combined with movement control, quarantine and stamping out. This strategy has been successful in drastically reducing the number of outbreaks during the past 5 years. However, HPAIV H5N1 is still circulating and is regularly isolated in traditional live bird markets (LBMs) where viral infection can persist, which represent a public health hazard for people visiting them. The use of social network analysis in combination with epidemiological surveillance in South China has identified areas where the success of current strategies for HPAI control in the poultry production sector may benefit from better knowledge of poultry trading patterns and the LBM network configuration as well as their capacity for maintaining HPAIV H5N1 infection. We produced a set of LBM network maps and estimated the associated risk of HPAIV H5N1 within LBMs and along poultry market chains, providing new insights into how live poultry trade and infection are intertwined. More specifically, our study provides evidence that several biosecurity factors such as daily cage cleaning, daily cage disinfection or manure processing contribute to a reduction in HPAIV H5N1 presence in LBMs. Of significant importance is that the results of our study also show the association between social network indicators and the presence of HPAIV H5N1 in specific network configurations such as the one represented by the counties of origin of the birds traded in LBMs. This new information could be used to develop more targeted and effective control interventions.

Bayesian estimation of the dynamics of pandemic (H1N1) 2009 influenza transmission in Queensland: A space–time SIR-based model

Background A pandemic strain of influenza A spread rapidly around the world in 2009, now referred to as pandemic (H1N1) 2009. This study aimed to examine the spatiotemporal variation in the transmission rate of pandemic (H1N1) 2009 associated with changes in local socio-environmental conditions from May 7–December 31, 2009, at a postal area level in Queensland, Australia. Method We used the data on laboratory-confirmed H1N1 cases to examine the spatiotemporal dynamics of transmission using a flexible Bayesian, space–time, Susceptible-Infected-Recovered (SIR) modelling approach. The model incorporated parameters describing spatiotemporal variation in H1N1 infection and local socio-environmental factors. Results The weekly transmission rate of pandemic (H1N1) 2009 was negatively associated with the weekly area-mean maximum temperature at a lag of 1 week (LMXT) (posterior mean: −0.341; 95% credible interval (CI): −0.370–−0.311) and the socio-economic index for area (SEIFA) (posterior mean: −0.003; 95% CI: −0.004–−0.001), and was positively associated with the product of LMXT and the weekly area-mean vapour pressure at a lag of 1 week (LVAP) (posterior mean: 0.008; 95% CI: 0.007–0.009). There was substantial spatiotemporal variation in transmission rate of pandemic (H1N1) 2009 across Queensland over the epidemic period. High random effects of estimated transmission rates were apparent in remote areas and some postal areas with higher proportion of indigenous populations and smaller overall populations. Conclusions Local SEIFA and local atmospheric conditions were associated with the transmission rate of pandemic (H1N1) 2009. The more populated regions displayed consistent and synchronized epidemics with low average transmission rates. The less populated regions had high average transmission rates with more variations during the H1N1 epidemic period.

Development of immunotherapies and vaccines against visceral leishmaiasis

Visceral leishmaniasis (VL) is a chronic parasitic disease prevalent in tropical and sub- tropical countries. This study focused on the development of immune-based therapy with immune checkpoint inhibitors and/or activators, as well as cytokines as a way to treat VL either alone or in combination with conventional drugs. Since many chronic infectious diseases share mechanisms of immune suppression, these findings have broader implications for other infectious diseases, such as HIV, tuberculosis and malaria.

Protection Conferred by Infectious Coryza Vaccines Against Emergent Avibacterium paragallinarum Serovar C-1

Infectious coryza is an upper respiratory disease of chickens caused by Avibacterium paragallinarum. Outbreaks of infectious coryza caused by Av. paragallinarum serovar C-1 isolates in coryza-vaccinated flocks in Ecuador and Mexico have been reported. In the current study, the protection conferred by four commercially available, trivalent infectious coryza vaccines in chickens challenged with a serovar C-1 isolate from an apparent coryza vaccine failure in a layer flock in Mexico was evaluated. Only one infectious coryza vaccine provided a good protection level (83%) in vaccinated chickens. These results might explain the infectious coryza outbreaks in vaccinated flocks that have been observed in the field.

Are organisations prepared for e-health implementation to respond to pandemic influenza?

E-health can facilitate communication and interactions among stakeholders involved in pandemic responses. Its implementation, nevertheless, represents a disruptive change in the healthcare workplace. Organisational preparedness assessment is an essential requirement prior to e-health implementation; including this step in the planning process can increase the chances of programme success. The objective of this study is to develop an e-health preparedness assessment model for pandemic influenza (EHPM4P). Following the Analytic Hierarchy Process (AHP), 20 contextual interviews were conducted with domain experts from May to September 2010. We examined the importance of all preparedness components within a fivedimensional hierarchical framework that was recently published. We also calculated the relative weight for each component at all levels of the hierarchy. This paper presents the hierarchical model (EHPM4P) that can be used to precisely assess healthcare organisational and providers' preparedness for e-health implementation and potentially maximise e-health benefits in the context of an influenza pandemic. Copyright © 2013 Inderscience Enterprises Ltd.