Tuesday, March 17, 2015

Modified "Kunjin Virus" Represents Another Lead in the Pursuit of an Ebola Vaccine

A collaborative team of researchers from Australia, France and Russia are attempting to create an Ebola virus vaccine by modifying a naturally-attenuated strain of West Nile virus from Australia called Kunjin virus.   These researchers have replaced structural genes in the Kunjin genome with a recombinant Ebola virus envelope glycoprotein (EBOV-GP).   This swapping of genomic content has two important implications for the effectiveness of the vaccine.  First, the loss of native Kunjin structural genes means the virus can replicate its genome inside the host cells it infects but it cannot generate new virion particles.  In other words, the vaccine virus cannot create a productive infection and therefore has only a transient presence in the host.  Theoretically, a transient presence of the vaccine virus could generate a host immune response and stimulate long-term immunological memory without endangering host health.  Second, the inclusion of Ebola glycoproteins in the modified Kunjin vaccine virus will train the host immune system to recognize and resist Ebola, conferring protection against Ebola.  Because envelope proteins like EBOV-GP are the viral elements host immune cells first encounter in a natural Ebola infection, recognition of those proteins and initiation of an immune response can confer protection against Ebola even if the host immune system does not have trained cells that recognize other molecular components of the actual Ebola virus.

Several other promising Ebola vaccine candidates use a similar strategy of gene-swapping in attenuated viruses to train the host immune system to recognize Ebola antigens.  GlaxoSmithKline and the National Institute of Allergy and Infectious Diseases (NIAID) have introduced EBOV-GP into a chimpanzee adenovirus that is being fast-tracked through phase 1 clinical trials due to the ongoing Ebola outbreak.  Similarly, NewLink Genetics has repurposed a vesicular stomatitis virus (VSV)-based chickenpox vaccine as an Ebola vaccine by swapping the chickenpox envelope protein gene introduced into the VSV genome for the EBOV-GP protein gene.  Hopefully one of these promising candidates will prove successful in clinical trials and be deployed in West Africa to stem the tide of Ebola cases in that region.

To read more about this vaccine candidate visit:  http://jid.oxfordjournals.org/content/early/2015/02/28/infdis.jiv019.full.pdf+html

--Laurie Rumker

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