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Novel live attenuated virus vaccine overview

About this type of vaccine

Live attenuated vaccines historically have been the most effective intervention in the fight to prevent infectious diseases. Such vaccines have eliminated smallpox from the entire globe and polio from the Western hemisphere. The incidence of measles, mumps, rubella, and chickenpox have been greatly reduced in those regions with high percentages of vaccinated individuals.

In addition to their efficacy, live attenuated vaccines are relatively inexpensive to produce. However, there is an extremely low but finite risk with all of these vaccines that they can revert to being virulent again. In the case of the Sabin polio vaccine, some circulating poliovirus strains that have caused local epidemics have been traced to vaccine revertants. This means that live attenuated vaccines are unlikely to be used for certain high profile lethal diseases.

GVI’s live attenuated chimeric virus vaccine

We have licensed a technology that allows directed molecular construction of live attenuated virus vaccines using a genetic component from one virus and the antigenic elements from the virus targeted by the vaccine. These chimeric vaccines are predicted to be safe, very unlikely to revert, and highly efficacious.

HIV Chimeric Virus Vaccine Program

The search for an HIV vaccine has been ongoing for decades. In all that time, only one approach has appeared to be strongly protective in the monkey model for AIDS, which is known as simian immunodeficiency virus (SIV). Deletion of a portion of the SIV genome resulted in a virus that could grow in cell culture but failed to cause AIDS in monkeys. When animals inoculated with this attenuated virus were challenged again with virulent SIV, they were protected from the otherwise lethal infection. The mechanism by which protection is mediated is likely to be through a T-cell response elicited by the first inoculation. Although this suggested that a live attenuated vaccine might protect against HIV, the approach was considered far too risky to try in humans.

We feel that given the urgency of finding a successful vaccine strategy for HIV, and that given the success of a live attenuated vaccine approach in monkeys, our approach to a live attenuated chimeric virus vaccine might be both safe and successful.

We have constructed a model chimeric vaccine consisting of an alphavirus-derived RNA genome containing the genes for the two major structural proteins of SIV. This allows the RNA to be packaged in what is essentially an SIV particle. The chimeric particle should appear to the immune system exactly like authentic SIV. It should grow in the body until an immune response suppresses its growth, leaving the animal protected against infection with authentic SIV. Unlike attenuated SIV however, the chimeric vaccine will not be able to integrate its genome into the chromosomes of the cell or produce a chronic infection.

We have developed assays to quantitate the chimera, demonstrated infection of cells that is strictly dependent on the specific SIV receptors, selected for improved growth in cell cultures and are now preparing to vaccinate monkeys with the model chimeric vaccine.

The chimeric vaccine approach should be applicable to other diseases, such as hepatitis C, where chronic infection by the virulent virus would preclude development of a live attenuated vaccine.

This program has been supported by the International AIDS Vaccine Initiative (IAVI) and through IAVI, the Bill and Melinda Gates Foundation’s Collaboration for AIDS Vaccine Discovery (CAVD).

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