Innate immunemodulator containing adjuvant formulated HA based vaccine protects mice from lethal infection of highly pathogenic avian influenza H5N1 virus.

The highly pathogenic avian influenza (HPAI) H5N1 viruses and their spillover into the human population pose substantial economic and public health threats. Although antiviral drugs have some effect in treating influenza infection, vaccination is still the most effective intervention to prevent possible pandemic outbreaks. We have developed a novel H5 influenza vaccine to improve the world's pandemic preparedness. We produced a hemagglutinin (HA) of HPAI H5N1 virus A/Alberta/01/2014 (AB14) using both mammalian (m) and bacterial (b) expression systems. The purified recombinant proteins were formulated with a proprietary adjuvant (TriAdj) and their efficacy as vaccine candidates was evaluated in mice. Intramuscular delivery of two doses of TriAdj formulated mammalian expressed HA (m-HA/TriAdj) was shown to provide full protection against a lethal challenge of AB14 in mice. In contrast, bacterially expressed HA with TriAdj (b-HA/TriAdj), b-HA without adjuvant, and m-HA without adjuvant resulted in no protection in immunized mice. Furthermore, m-HA/TriAdj elicited significantly higher levels of balanced Th1 and Th2 responses and neutralizing antibody titres. All the mice in the m-HA/TriAdj group survived a lethal AB14 H5N1 challenge and showed no signs of disease or infection as demonstrated by no loss of body weight or detectable virus in the lungs. Our results suggest that m-HA formulated with TriAdj has potential to protect against pandemic H5N1 in the event of its cross over to the human host.

Retro-inversion enhances the adjuvant and CpG co-adjuvant activity of host defence peptide Bac2A.

Host defence peptides (HDPs) have a variety of potential therapeutic applications, including as vaccine adjuvants, energizing efforts for modification strategies to address their toxicity and instability. Here we compare l, d and RI-Bac2A as vaccine adjuvants. d and RI-Bac2A are equally resistant to proteolytic degradation with no increases in toxicity, however, only RI-Bac2A maintains adjuvant activity of the natural peptide through conserved induction of a Th2 immune response. As HDPs potentiate the adjuvant activity of CpG ODNs, the isomers were also evaluated as co-adjuvants. l-Bac2A has no significant co-adjuvant activity while CpG/RI-Bac2A induces antibody titres significantly higher than CpG (P<0.01), CpG/l-Bac2A (P<0.01) or CpG/d-Bac2A (P<0.01). None of the isomers influence ODN duration or distribution but l and RI-Bac2A promote ODN uptake into B cells and antigen presenting cells. The enhanced adjuvant and co-adjuvant of RI-Bac2A is hypothesized to result from an undefined combination of increased stability and retained biological activity supporting application of retro-inversion to this, and potentially other HDPs.

Veterinary vaccines: alternatives to antibiotics?

The prevention of infectious diseases of animals by vaccination has been routinely practiced for decades and has proved to be one of the most cost-effective methods of disease control. However, since the pioneering work of Pasteur in the 1880s, the composition of veterinary vaccines has changed very little from a conceptual perspective and this has, in turn, limited their application in areas such as the control of chronic infectious diseases. New technologies in the areas of vaccine formulation and delivery as well as our increased knowledge of disease pathogenesis and the host responses associated with protection from disease offer promising alternatives for vaccine formulation as well as targets for the prevention of bacterial disease. These new vaccines have the potential to lessen our reliance on antibiotics for disease control, but will only reach their full potential when used in combination with other intervention strategies.

Use of animal models in the development of human vaccines.

Over the past 100 years, animal infectious disease research has played a crucial role in the development of human vaccines. In fact, many of today's vaccines are based on utilizing animal pathogens, either in the form of an attenuated vaccine or as a vaccine vector. Vaccine development has become increasingly complex with chronic and newly emerging diseases, a demand for therapeutic vaccines for noninfectious diseases, extended vaccine in the neonate and the elderly, and increasing concerns regarding vaccine safety. Furthermore, the evaluation of quantity and quality of immune responses and the ability to efficiently translate the results of basic research into the clinic are critical to ensure that vaccines meet their therapeutic potential. Here, we review the importance of animal models for developing and testing novel human vaccines, discuss the limitations of existing animal models in knowledge translation, and summarize the needs and criteria for future animal models. We argue that efficient translation of basic vaccine research to clinical therapies will depend upon the availability of appropriate animal models to address each of the questions which arise during vaccine development.