The new face of vaccines - thank your neighborhood moth!

Did you know that cells from the ovaries of the moth Spodoptera frugiperda are now being used by scientists, as tiny factories to produce very important proteins? Welcome to the new technologies for vaccine development!

Immunizing people against a number of diseases is a well-established protocol, recognized and recommended by the WHO and other medical agencies. However, it remains a matter of contention for a small number of people.
 
In this recent Tilde Cafe discussion, Dr. Rachael Felberbaum outlined the history of vaccines and brought us into the 21st century with the story of how moths, and viruses that infect moths, are being used to benefit us in rapidly making effective vaccines, with fewer side-effects.

According to several sources, variolation — a method to immunize an individual against the smallpox virus (Variola), that involves taking material from an infected individual and applying it to an uninfected individual — was well established in Asia and the Middle East, long before Edward Jenner conducted his historic experiment in 1796. Jenner had used the pus from a milkmaid infected with cowpox, and applied it to an incision on child’s arm, which subsequently made the boy immune to smallpox. This was 220 years ago. We now know that only a fraction of all the proteins in a virus (in this instance the virus was in the pus) are responsible for a disease.
 
The science and technology underlying vaccine development has been relatively unchanged when compared to other biomedical advances. After Jenner’s work at the end of the 18th century, Louis Pasteur made a significant modification when he developed a vaccine against rabies: whereas Jenner had triggered protection to smallpox using live virus from the pus of a person infected with another less virulent disease (cowpox), Pasteur reduced the virulence (severity of infection) of the rabies virus by letting it dry out before administering it to a young boy who had been mauled by a dog. This was almost 100 years after Jenner’s experiments.

The next major innovations in vaccine development came in a burst about 70 years later, and a leading force in these efforts was Maurice Hilleman and his colleagues at E.R. Squibb and Sons (now Bristol-Myers Squibb), and later at Merck & Co. Over the course of his career, Hilleman developed 40 vaccines, 14 of which are currently on recommended vaccine schedules.
 
So, following Pasteur’s work, vaccines typically contained either live-attenuated viruses (resulting in reduced virulence of the virus) — such as the measles, mumps, rubella, flu and chickenpox vaccines; or viruses that had been inactivated by either heat, radiation or chemicals — such as the polio and hepatitis A vaccines. Irrespective of whether a vaccine is made of a live-attenuated virus, or an inactivated one, the initial steps involve infecting chicken eggs and then harvesting the virus particles from them. This has been a tried and tested method, but it is an expensive and cumbersome process because in many instances, one egg yields only one dose of a vaccine and it contains not just the infectious part of the virus, but other non-infectious viral proteins. The little chicken embryo is thus doing a lot of work making viral proteins that are useful to us, but also viral proteins that are of no use to us.
 
With advances in molecular biology which have enabled producing pure proteins for a variety of uses, the obvious next step was to develop a system to manufacture only the infectious part of the virus. Enter our favourite moth. Spodoptera frugiperda. Using a virus that only infects insect cells, and cannot infect mammalian cells, researchers have engineered that virus — a baculovirus — to contain the gene that codes for the infectious protein of interest. This bioengineered virus can then be made to infect the insect cells in large vat-like bioreactors where the virus hijacks the insect cell’s machinery, directing it to make all the proteins in the bioengineered baculovirus. The little insect cell factories churn out large amounts of the infectious viral protein, which is then purified and carefully processed for human use. Making vaccines using these 21st century technologies is not only more cost efficient and safe, but the time from start to finish is a fraction of that required for traditional vaccine production.

Currently, a few proteins made using the baculovirus:moth-ovary cell system are being tested for a variety of applications including vaccines and gene therapy. In 2013, FDA approved the first vaccine made using this technology for use by adults — Flublok. Because of the efficiency of the system, it is also being exploited to design vaccines for Zika and other viral diseases. A swift response to epidemics is critical in our increasingly mobile world — we are currently witnessing new outbreaks of polio in Nigeria, and yellow fever in the Democratic Republic of Congo. To have a quick and steady supply of vaccines for these and future outbreaks, it is not enough to rely on old technologies; instead new technologies such as described by Rachael, as well as continued innovations, are extremely important. Equally important is educating society about the importance of vaccines and vaccinations, as underscored by Dr. Felberbaum last week, and Professor Iwasaki last year.

For those who are mottephobes, or even those who have wondered about the raison d’être for moths — other than destroying your woolies — moths can give you a better life!

And in closing, here’s a silly moth-plus-biotechnology joke/riddle:

What do you get if you cross a firefly and a moth?
An insect who can find its way around a dark wardrobe!