Pitt scientists use novel biomedical technology to ramp up the production of swine flu vaccines

June 19, 12:48 PMPittsburgh Medical Technology ExaminerRuben Dagda

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(University of Pittsburgh)

     Since the number of swine flu related cases has surpassed the 30,000 mark a week ago, the World Health Organization has raised the status of the swine flu pandemic to level 6.  Back in May, one of my articles highlighted the  strategies developed by epidemiologists and public health officials in Pennsylvania around the world to solve this health crisis. It is worrisome that the number of swine-flu reported cases have increased in Allegheny Pennsylvania alone in the past couple of weeks, giving a somber indication that many people who are pre-symptomatic carriers of swine flu may actually develop the disease this winter. As a testament of this observation, there has been a dramatic rise in the number of confirmed cases from 40  to 1024 in one month (a 20-fold increase from May 20 to June 20). Keep in mind that this tally does not include the number of unreported cases or asymptomatic carriers that can infect more people.
     In order to counter a predicted dramatic rise in swine flu case for the upcoming winter, the Center for Vaccine Research at the University of Pittsburgh, one of 13 sophisticated and top-notch centers founded three years ago for the purpose of fighting world-wide pandemics, has employed a novel molecular biology technique that will be used for rapidly and efficiently scale up the production of flu vaccines compared to conventional methods. In January of this year, the Center for Vaccine Research strategically initially geared production of a vaccine targeted against the H5N1 virus, a virus which causes the avian flu and is of still great concern. However, the outbreak of the H1N1 swine flu virus in April obligated the organization to shift its strategy toward producing a new prototype of the swine flu virus vaccine also. What will happen this winter is a black box at this point. There is a lingering fear among scientists and epidemiologists that the “apparent” latency of the virus exhibited during this summer may eventually resurface this winter into a full-blown and uncontrollable second wave of swine flu and clinical symptoms may be actually manifested in millions of asymptomatic carriers.

    Traditionally, flu vaccines are developed by infecting fertilized chicken eggs followed by heat or chemical inactivation of the virus. This process is slow, tedious and time-consuming which requires about six months produce a flu vaccine, a timeline that does not meet the high world-wide demand for swine flu vaccines. It is conceivable that millions of people may be infected and develop the disease by the time a swine flue vaccine is generated by conventional methods of vaccine production and distributed to medical clinics and hospitals. However, there is an alternate solution that offers more than glimmer of hope. The University of Pittsburgh Center for Vaccine Research , in addition to a few other academic institutions in the country, have adopted an alternate technique that cuts down the amount of production costs and the time to create a prototype and efficiently up-scales vaccine production. 

    The new protocol involves generating vaccines that consists of virus-like particles (VLPs) which induce a stronger and longer-lasting immune response against flu viruses than conventional vaccines. Virus like particles (VLPs) consist of structural related proteins that form the outer shell and surface proteins which may or may not be imbedded in lipid bilayers. However, unlike conventional methods that generates vaccines using “whole” virus”, the 3D structure of virus like particles do not completely resemble the infectious virus but are hollow shells that lack the RNA required for replication. In other words, VLPs are essentially harmless, non-infectious, replication-deficient virus used for immunization. Moreover, unlike conventional vaccines, VLPs are more efficient in eliciting both T cell and B cell immune responses. As of right now, VLP vaccines have been successfully created for the papilloma and the hepatitis C virus. Moreover, the US Army Medical Research Institute of Infectious Diseases have used this method successfully developed an Ebola vaccine using VLPs and was successful in  preventing both the infection and the development of hemorrhagic fever in mice. As a token of fortune, the viral genome of the H1N1 virus has been already sequenced weeks before the swine flu was considered a global pandemic. Thus by knowing the H1N1 genome and by using molecular biology techniques, Pittsburgh scientists are able express only certain key structural proteins or the complete outer shells of the H1N1 virus in mammalian cells. The viral coat proteins are then extracted from infected mammalian cells, purified by ultraspeed centrifugation techniques and VLPs may be chopped into little protein pieces by enzymatic digestion. The resulting extract of VLP is then used to immunize individuals to boost their immune systems.

    Although there are a few remaining skeptics who question the efficacy of VLP vaccines, Ted Ross, a University of Pittsburgh's Center for Vaccine Research assistant professor, has claimed that a couple of on-going promising clinical trials have shown that vaccines employing VLPs exert protection against two known threats: the 1918 Spanish influenza virus and the H5N1 avian influenza virus. Thus, this novel method of vaccine production allows public health officials to respond more quickly to unexpected influenza pandemics. It is now plausible to generate VLP vaccines in mass quantities in as little as 12 weeks compared to conventional vaccines which require up-to nine months. An additional caveat of conventional vaccines is that it requires the physical isolation of whole virus from infected individuals or a site of investigation whereas knowing the DNA sequence of the whole genome, or a few key structural coat proteins and/or receptors may be sufficient to create VLP vaccines. More importantly, since all influenza viruses rapidly mutate and giving rise to multiple strains each year that cause human flu, this novel protocol allows the sufficient flexibility and time to generate more swine flu vaccines in the case that any influenza strain undergoes mutations. Although the full-blown resurgence of the H1N1 influenza is expected to happen this winter, VLP vaccines and the creation of more "strategic vaccine research centers" will definitely counteract and lower the rate of mortality.
 

a. Press release regarding influenza vaccine production in Western Pennsylvania:    pittsburgh.bizjournals.com/pittsburgh/stories/2009/05/11/story1.html

b. Production of viral-like particle vaccines in Pittsburgh:  www.biologynews.net/archives/2009/05/18/new_vaccine_strategy_might_offer_protection_against_pandemic_influenza_strains.html 

c.  Production strategies of H5N1 vaccines in Pittsburgh: www.upmc.com/MediaRelations/NewsReleases/2006/Pages/PromisingAvianFluVaccine.aspx