Arbovax’s unique strategy for vaccine development is based on production of stable mutations of insect-vectored viruses that are capable of successful replication in insect cells but that yield only abortive infections in mammalian cells. Successful development of these mutations has resulted in new methods for the production of vaccine strains of an important class of human and animal pathogens.

Research conducted in Dr. Brown’s laboratory demonstrated dramatic differences in both the process of virus assembly in insect and mammalian cells and in the way that mammalian and insect cells respond to virus infection. The Company’s R&D plan is based upon the assumption that the differences observed in the process of virus replication and host response reflect fundamental differences in the biology of the vertebrate and invertebrate cells. These differences have been exploited to develop a method for production of viral mutants that are capable of efficient replication in the invertebrate cell but are incapable of productive replication in vertebrate cells. These mutants are the basis for the development of vaccines against insect-vectored, membrane-containing viruses.

Membranes of insect cells differ dramatically from those of mammalian cells in both chemical composition and structural properties. Membranes of viruses produced in these cells reflect those differences. Insect cell membranes are thinner in cross-section than the membranes of mammals because insects have no cholesterol in their membranes. Membrane-spanning domains of proteins integrated into insect membranes do not need to be as long as those integrated into the membranes of mammals.

Using molecular cloning techniques we have produced deletion mutations in the membrane-spanning domains of viral envelope glycoproteins. These mutations restrict the ability of the virus to replicate to the cells of the insect host. Virus produced from insect cells can infect mammals but do not produce significant progeny virus. The result is development of immunity in the absence of disease.

The diagram below graphically illustrates the procedure as applied to Sindbis virus.

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