Review about vaccine technologies

[Ganseerpel]

Prevention
Making Better Influenza Virus Vaccines?

Peter Palese*<SUP></SUP>
*Mount Sinai School of Medicine, New York, New York, USA
Suggested citation for this article
<HR>

Killed and live influenza virus vaccines are effective in preventing and curbing the spread of disease, but new technologies such as reverse genetics could be used to improve them and to shorten the lengthy process of preparing vaccine seed viruses. By taking advantage of these new technologies, we could develop live vaccines that would be safe, cross-protective against variant strains, and require less virus per dose than conventional vaccines. Furthermore, pandemic vaccines against highly virulent strains such as the H5N1 virus can only be generated by reverse genetics techniques. Other technologic breakthroughs should result in effective adjuvants for use with killed and live vaccines, increasing the number of available doses. Finally, universal influenza virus vaccines seem to be within reach. These new strategies will be successful if they are supported by regulatory agencies and if a robust market for influenza virus vaccines against interpandemic and pandemic threats is made and sustained.

FText: http://www.cdc.gov/ncidod/EID/vol12no01/05-1043.htm

[kent nickell]

Re: Review about vaccine technologies

Excellent vaccine article... I highlighted a few things...

To allow sufficient time for manufacture, in the United States the US Food and Drug Administration (FDA) determines in February which vaccine strains should be included in the following winter's vaccine. Unfortunately, FDA recommendations are not always optimal. For example, in 2003 FDA rejected the use of the most appropriate H3N2 strain, A/Fujian/411/2002, and instead again used the same strain as in the 2002 formulation. This decision was made primarily because the A/Fujian/411/2002 strain had first been isolated in Madin Darby canine kidney (MDCK) cells rather than in embryonated eggs. Use of MDCK cells for virus isolation is not allowed by FDA's rules, which do not yet encompass advanced technologies or scientifically sound purification procedures based on limiting dilutions or cloning with DNA. Because of this bureaucratic roadblock, the H3N2 component of the 2003?2004 influenza virus vaccine was antigenically "off" and showed suboptimal efficacy. One hundred fifty-three pediatric deaths were associated with influenza infections during the 2003?2004 season in 40 states, whereas only 9 such deaths had been reported in the following season ( 3). Also, because the cumbersome classical reassortment technique used for preparing the appropriate seed strains makes the yearly process of manufacturing influenza virus vaccines unnecessarily lengthy, new variants first appearing early in the season are rarely considered for the vaccine formulation of the following winter.

As indicated, current FDA-licensed influenza vaccines are based on technologies developed in the 1960s and earlier. Through the breakthrough of reverse genetics techniques ( 13?15), infectious influenza viruses from plasmid DNAs transfected into tissue culture cells can now be rescued. This technology permits the construction of high-yield 6:2 seed viruses by mixing the 6 plasmid DNAs from a good-growing laboratory strain with the HA and NA DNAs obtained by cloning relevant genes from currently circulating viruses. Thus, within a 1- to 2-week period, the appropriate seed viruses could be generated for distribution to the manufacturers.

Such an approach would have several advantages over the present manufacturing process. First, it would dramatically accelerate the timeframe for obtaining seed viruses for annual production and thus allow more time to select the appropriate antigenic seed strains.

By engineering a virus with intermediate virulence and ability to induce interferon, one can construct ideal influenza virus vaccines that are both attenuated and highly immunogenic ( 17?20).

This process should translate into lower doses of live virus vaccine required to induce a robust and protective immune response. If a hundredfold lower dose is required, many more people could have access to influenza virus vaccines. This issue is clearly of paramount importance in the event of a new pandemic virus. Moreover, a live virus vaccine may give protective immunity in immunologically naive populations after a single administration,

Because live influenza virus vaccines appear to be more effective in immunologically naive populations and they can be intranasally administered, they would represent a more economical way of vaccinating large numbers of people.

Conclusions
Technologies are now in place to design and construct new influenza virus vaccines that have the potential to be cheaper and more cross-protective than current vaccine preparations, while at the same time being equally safe. The greatest problems for new and better vaccines appear to be associated with regulatory hurdles and the lack of an adequate market. Regarding the bureaucratic restrictions levied on vaccines by licensing agencies, the message has to come through "that small risks have to be tolerated for larger ones to be avoided" ( 34). Also, the message needs to be disseminated to the general public that vaccines have the best cost-benefit ratio of any medical treatment and that limitations of the tort law should be considered where vaccines are concerned. The public often views vaccines and prophylactic treatments in general as being of low priority. Many people also believe they should be free. Thus, the absence of a robust commercial market is a major difficulty, resulting in slow progress for research and development of new influenza vaccines and in dangerously thin supply lines. In fact, we are far from being prepared to deal with regular influenza outbreaks, and adequate measures to cope with a pandemic outbreak are only now being considered, but are not yet in place ( 35,36; and http://www.washingtonpost.com/wp-dyn...110101100.html ).

[gsgs]

Re: Review about vaccine technologies

he doesn't mention that actual flu-vaccinations of the general
population have little effect
and have been recommended to be abandonned.

[Jefferson et.al Cochrane database review, multy-study]