Abstract
Despite the fact that there had been multiple small outbreaks of Ebola Virus Disease, when a large outbreak occurred in 2014 there were no vaccines or drugs available for use. Clinical development of multiple candidate vaccines was then initiated in parallel with attempts to contain the outbreak but only one vaccine was eventually tested in a phase III trial. In order to be better prepared for future outbreaks of known human pathogens, platform technologies to accelerate vaccine development should be employed, allowing vaccine developers to take advantage of detailed knowledge of the vaccine platform and facilitating rapid progress to clinical trials and eventually to vaccine stockpiles. This review gives an example of one such vaccine platform, replication-deficient simian adenoviruses, and describes progress in human and livestock vaccine development for three outbreak pathogens, Ebola virus, Rift Valley Fever Virus and Middle East Respiratory Syndrome Coronavirus.
Highlights
Replication-deficient adenoviral vectors were originally developed for gene therapy applications, as they can be produced in an efficient manufacturing process, are able to infect cells expressing the coxsackie and adenovirus receptor (CAR) and express the encoded gene of interest within the infected cell
Human adenoviruses are highly immunogenic in mice and other species but as many humans have previously been infected by common human adenoviruses such as AdHu5, anti-vector antibodies generated after the initial infection can neutralise a vaccine based on the same adenovirus, reducing immunogenicity
A replicationdeficient human adenovirus 5 vaccine was protective in the same non-human primates (NHP) challenge model [6] but in a clinical trial, pre-existing immunity to the vaccine vector resulted in variable immune responses to the Ebola glycoprotein [7], with the result that the ChAd3-vectored vaccine, with very low pre-existing immunity to the vaccine vector was the preferred option for further clinical testing
Summary
Replication-deficient adenoviral vectors were originally developed for gene therapy applications, as they can be produced in an efficient manufacturing process, are able to infect cells expressing the coxsackie and adenovirus receptor (CAR) and express the encoded gene of interest within the infected cell. Human adenoviruses are highly immunogenic in mice and other species but as many humans have previously been infected by common human adenoviruses such as AdHu5, anti-vector antibodies generated after the initial infection can neutralise a vaccine based on the same adenovirus, reducing immunogenicity. The level of neutralising antibodies to simian adenoviruses is very low in human populations, and a number of differ-. Ent replication-deficient vaccine vectors such as ChAd3, ChAd63 [1] and ChAdOx1 [2] have been developed from simian adenoviruses
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