23 October 2009

Vaccines based on virus–like particles - fast, effective, safe

The excitement around the H1N1 flu (the so-called "swine flu") has increased the interest of the scientific community in a new type of vaccines, the active component of which are virus-like particles (VLP). Such vaccines, thanks to the speed of manufacture, should solve the long-standing problem of the timely appearance of vaccines against the rapidly mutating influenza virus.

The key biomedical feature of the VLP vaccine is the nature of the antigen - the component that causes the development of an immune response in a vaccinated individual. VLP vaccines do not include traditionally used killed or weakened viruses, but small protein structures grown in plants or insects. For the body's immune system, they look like real viruses, but they do not contain viral genetic material.

The virus-like particle (above), in fact, is a copy of the virus envelope, which, in the absence of genetic material, does not pose any danger to the body. The absence of genetic material also excludes formalin and detergent treatment from the production process, which is necessary for the neutralization of viruses, but weakens the immunogenicity of viral antigens.

However, the most important advantage of VLP vaccines is the speed of their production. The finished vaccine can be made available to doctors as early as 3-4 months after the outbreak is registered and the genetic sequence of the virus is deciphered. This achievement is very significant compared to the 7 months that, despite the panic in the media, it took to develop a vaccine against the H1N1 influenza virus.

Virus-like particles have been talked about as a promising approach for more than 20 years. It seems that in the near future they will finally make mankind happy with their appearance. Over the past decade, scientists have solved almost all production and technical problems, starting from the creation of effective antigens and ending with their mass production. The decisive step was to obtain approval from the US Food and Drug Administration for the first VLP vaccine Gardasil, which is also the first effective vaccine against human papillomavirus, which causes the appearance of genital warts and is associated with cervical cancer. This event was a real breakthrough, as the US Food and Drug Administration, which is very conservative with regard to vaccines, recognized the safety of VLP vaccines.

After that, the development of influenza VLP vaccines quickly gained momentum. VLP vaccines against avian, swine and seasonal influenza, as well as against Ebola hemorrhagic fever, have already shown good results in animal experiments. This month, two leading developers of influenza VLP vaccines, Novavax (Maryland, USA) and Medicago (Quebec, Canada), are already starting clinical trials of two influenza VLP vaccines. Several more vaccines have been successfully tested on animals and are waiting for their turn.

Companies use different manufacturing processes in the manufacture of their vaccines. Medicago grows virus-like particles in transgenic tobacco plants that are easily manipulated, do not require special care and grow quickly in high-tech greenhouses that can be built in almost any conditions. The company's specialists inject genetic information about the virus envelope proteins into fully formed tobacco plants, after which the plants begin to produce these viral envelopes in their cells. After a few weeks, the biomass is harvested and processed in order to isolate virus-like particles.

Novavax chose a different approach – the use of insect cell cultures. The company's specialists grow virus-like particles in a line of identical "immortalized" cells isolated 20 years ago from the body of a grass scooper caterpillar (Spodoptera frugiperda). Baculovirus is injected into caterpillar cells – a virus that infects only insects – modified to resemble the flu virus. Cells respond to such interference by producing and secreting virus-like particles similar to those of the influenza virus, but lacking viral RNA.

Compared to traditional methods, these technologies are low-cost and require little time. For clarity, we will give the following facts: this week Novavax started phase 1 of a clinical trial of an experimental swine flu vaccine with the participation of 400 people. The genetic sequence of the H1N1 virus was deciphered in early May of this year, since then the company's specialists have developed a technology for the production of virus-like particles, launched their small-scale production and tested the finished product on animals. During this period, manufacturers of traditional vaccines have just begun to supply the first batches of drugs that did not require either fresh developments or animal testing, but only minimal testing with the participation of volunteers.

Of course, the production of VLP vaccines may still face various difficulties. However, judging by the results already obtained, if the current research does not reveal any fundamental flaw in the approach, VLP vaccines will soon satisfy the need of humanity for effective, safe and timely protection against epidemics of influenza and other diseases.

Evgenia Ryabtseva, Alexander Chubenko
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Technology Review: Delivering a Virus Imposter Quicker.

23.10.2009

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