Structural-based designed modular capsomere comprising HA1 as low-cost poultry influenza vaccine

Conference Dates

June 12-17, 2016


Influenza is a severe respiratory tract infection caused by influenza viruses. The increasing number of highly pathogenic avian influenza (HPAI) virus outbreaks, generally H5 and H7 subtypes, underlines the threat of a possible pandemic. The recent HPAI H5 outbreak in domestic poultry and wild birds in US from December 2014 to June 2015, affecting almost 50 million birds and resulting in $3.3 billion economic losses due to the death and culling of poultry, has demonstrated the lack of capabilities to control the rapid spread of avian influenza. Poultry vaccination has been shown to not only reduce the virus spread in animals but also reduce the virus transmission to humans, preventing potential pandemic development. However, existing vaccine technologies could not respond to a new virus outbreak rapidly and at a cost and scale that is commercially viable for mass poultry vaccination. Here, we developed modular capsomeres, building blocks of virus-like particle, as a low-cost poultry influenza vaccine. Modified murine polyomavirus (MuPyV) VP1 capsomere was used to present structural-based designed influenza Hemagglutinin (HA1) antigen. Six constructs of modular capsomeres presenting three truncated versions of HA1 and two constructs of modular capsomeres presenting non-modified HA1 have been generated. Modular capsomeres presenting HA1 were successfully produced in stable forms using Escherichia coli, without the need for protein refolding process. This adjuvanted modular capsomere (CapHA1) induced strong antibody responses (almost 105 endpoint titre) when administered into chickens, similar to titres obtained in the group administered with insect cell-based HA1 proteins. Based on our process simulation, 320 million doses of modular capsomere vaccines can be produced in 2.3 days, at a cost of less than 1 cent per dose. The result presented here indicated that this platform for bacterially-produced modular capsomere could potentially translate into a rapid-response and low-cost vaccine manufacturing technology suitable for poultry vaccination.

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