A Different Vaccine Approach

Traditional vaccines are reliant on a few primary approaches: empirically weakened Live Attenuated Virus (LAV), inactivated (killed) forms of the virus, or created from the pathogen’s individual protein components (subunit vaccines) through protein purification, recombinant technology methods, or a combination of both.

Vacunax takes a phylogenetic approach to identify key virus evolutionary elements that are target for recombinant modifications to produce a safe, host-range limited LAV (HR-LAV) vaccine. Vacunax identified phylogenetic information that codes for key structural elements of the transmembrane domain of arbovirus spike proteins which have evolved in length to span both the thinner invertebrate membrane, and thicker cholesterol containing vertebrate membranes. Removing specific amino acids from this transmembrane domain results in species restricted viruses which grow efficiently in insect cells, but produces very limited amounts of non-infectious (inactive) particles in vertebrate cells.

How It Works

Arbovirus diseases in humans originated as insect (invertebrate) viruses which evolved to overcome host range barriers to infection to facilitate cross-species transmission to a vertebrate host as part of their life cycle. The Vacunax vaccine platform is based on interfering with the key membrane structural elements of arbovirus assembly that are crucial to their cross-species replication.

Source: Arboviral Encephalitis by Guey-Chuen Perng and Wei-June Chen. Submitted: May 20th 2012. Reviewed: August 15th 2012. Published: January 9th 2013. DOI: 10.5772/52327

One of the important differences between vertebrate and invertebrate cells is the composition of the cell membrane bilayer from which maturing virus “bud”. Vacunax technology takes advantage of the lack of cholesterol in insect cell membranes, which makes them much thinner than vertebrate membranes.

This led Vacunax to identify genetic information that codes for structural elements of the transmembrane domain of arbovirus spike proteins which have evolved in length to span both the thinner invertebrate membrane, and thicker cholesterol containing vertebrate membranes. Removing key amino acids from this transmembrane domain results in species restricted viruses which grow efficiently in insect cells, but primarily produce large amounts of non-infectious (inactive) particles in vertebrate cells.

HR-LAV: The Better Vaccine Strategy

The goal of vaccination is to stimulate protective immunity while avoiding adverse events from the vaccine itself. Live Attenuated Vaccines (LAV), when possible and available, are the most complete and effective vaccines, for these activate both, antibodies and cell-mediated responses, and are the closest we can get from a natural infection without the disease.

However, past attenuation processes were unpredictable, not always applicable, and limited by safety concerns, primarily of which is reversion to wild-type virulence.

Although inactivated virus and subunit vaccines alleviate many of the safety concerns for LAV vaccines, in general they have poor immunogenicity, do not produce long lasting immunity, requiring multiple booster doses to sustain benefit, and thus are less efficacious than their LAV counterparts.

The Vacunax HR-LAV variants contain large genetic deletions, making reversion to wild-type virulence impossible. In the laboratory, and in animal trials, no wild-type reversions have been detected. As the non-infectious particles produced by SC-LAV in vertebrate hosts contain all the proteins of wild-type virus, they are found to stimulate both a robust and antigenically varied primary antibody response, as well as the full “wild-type” cellular response in vertebrate animals.

By fully mimicking the natural disease process the Vacunax HR-LAV vaccine technology provides immediate, sustained and long term protection from pathogenic virus infection.

Using this HR-LAV host range mutation strategy, Vacunax has produced vaccines for dengue (flavivirus), chikungunya (alphavirus) fever, and Zika virus, which have had very successful preclinical trials in mice and/or monkeys (ref). Vacunax can produce vaccines against any Arbovirus (insect vectored viruses) that contains a membrane bilayer, a group of viruses that cause over 150 zoonotic diseases in humans and in many domestic animals.

Benefits

Species replication barrier insures no possibility of reversion to wild type virulence

Optimal immunity conferred against full virus proteins, structural and non-structural

 

Single dose, sustained immune response for years or life long depending on virus

High throughput production by stirred-tank bioreactors (no fixed substrate required), and lower manufacturing cost.

Lyophilized for easier storage
and transport