FYI...Gardisal and Cervarix are VLP's which are very very...

FYI...Gardisal and Cervarix are VLP's which are very very different to oral vaccines.

Oral vaccines for HPV/cervical cancer have more or less not moved forward in development for the past 5 years or so and with no meaningful funding provided and for a reason.

This IMO is why PRR may be able to secure a development project in this area on what at face value appears favourable terms and creates a sexy equity story to the ill informed.

If Ian Frazer gives this development program a glowing endorsement I will gladly eat my words and be completely behind this in-licensed program and may even buy into PRR at current levels.

Rgds

Prof

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There has been a great deal of effort to promote the production of an oral HPV vaccine in food plants or tobacco. The belief has been that the plant based oral vaccines would be cheap to produce for the developing world where the need for the vaccine is the greatest. Tobacco plants were modified to produce HPV 16 protein and produced sufficient antigen to elicit a weak immune response in rabbits [11]. Tobacco and potato were used to produce HPV 16 virus like particles. Feeding transgenic potato tubers to mice produced an LI antibody response in only 3 of 24 mice and that response was transient [12]. The oral administration of HPV-like particles produced in potato produced a weak immune response in mice, which was enhanced by oral boosting with virus-like particles produced in insect cell culture [13]. A vaccine against the papilloma virus oncogene product causing human cervical cancer was produced using a potato virus-X vector carrying an antigen of the viral oncogene-encoded protein [14]. These cancer vaccines are an important effort to control cancer, but environmental release of the vaccines in crop plants could greatly increase people’s susceptibility to specific cancers through the development of oral tolerance.

Plant-based vaccines are mainly geared towards mucosal immunization following oral intake. Oral vaccines may elicit oral tolerance on repetitive exposure. Oral tolerance is the animal’s response to antigens in food. Thus, after repeated exposure to an oral antigen, the mucosal immune system ceases to view the antigen as foreign, leaving the animal susceptible to the pathogen for which the vaccine is supposed to protect against [15]. The problem of oral tolerance has been mentioned in at least one review of plant-based vaccines [16]. Oral tolerance to pathogens is one main threat from the contamination of our food supply with vaccine genes, this threat is seldom discussed by promoters of plant genetic modification or by science journals reporting the studies.

Last year, I pointed out the drawbacks of using food crops to produce vaccines or therapeutic antibodies [17]. Genes from tests sites or production farms can be spread by pollen or mechanical dispersal of seeds. Debris from transgenic crops producing the antibody can spread both the genes and the vaccine proteins by contaminating surface and groundwater. Such debris may also spread with dust in the air, impacting on the airway mucosa directly. The plant-based systems for producing HPV 16 L1 vaccine included potato & tobacco, and banana, maize and rice have been discussed as systems for producing the vaccine.

The fission yeast S. pombe developed to produce HPV vaccine is also of questionable safety. Pombe beer is produced locally in many parts of Africa and pollution of that yeast with vaccine genes is a strong possibility should the recombinant yeast be dispersed widely. Exposure of an entire population of women and men of all ages to oral immunization with polluted crops, beer, water or air would lead to untoward consequences. A single exposure to antigen might immunize both females and males, possibly limiting males as virus vectors and protect females from infection as well. However, constant exposure to viral antigen would likely cause oral tolerance rendering females defenseless against the virus and rendering males strong vectors for the cancer virus.

In conclusion, the HPV recombinant vaccines produced in protected laboratory environments pose little obvious threat to humans or to the environment. The virus-like structures making up the vaccine do not contain DNA and cannot be replicated in the cell. In the event that trans-capsidation (virus DNA being incorporated into the vaccine structures) took place the recombinant virus would replicate only the original DNA and protein of the capsid. However, once oral vaccines are produced in crop plants or in yeast, there is a distinct danger of oral tolerance developing that not only cancels out the protective effects of the vaccine against infection, but could also leave females absolutely defenseless against the virus while turning males into carriers spreading the virus.

The recombinant vaccines producing viral proteins without viral DNA are acceptable, but production of oral vaccines in plants or yeast should be banned.