Human Papillomavirus Vaccine against Cervical Cancer

Cervical cancer is a disease affecting 500,000 women globally, claiming more than a quarter of a million lives a year. It is mainly caused by infection with the human papillomavirus (HPV). Only certain types of HPV (from a family of 100 related viruses), that are persistent and that survive the response of the immune system, lead to the formation of cancer. 1 Research has concluded that 2 types (high-risk) of HPV- 16 and 18 are associated with nearly 70% cervical cancer cases. 2The HPV is usually sexually transmitted. 1 With the advancement in science and technology, HPV vaccines have been constructed and approved by the U.S FDA. The HPV vaccine can prevent cervical cancer and other medical conditions such as genital warts, which are also caused by certain strains of HPV.
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The HPV vaccine developed is a subunit, recombinant vaccine which produces

antibodies in the host and targets the viruss major capsid protein- L1, when infection occurs. These antibodies are produced by immunizing the body with virus-like particles (VLP) that assemble by themselves following the expression of the L1 protein in a recombinant vector.
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These VLP are safe to use as a vaccine because they do not have

viral DNA and therefore cannot induce an infection in the recipient. A research study shows that the HPV 16 L1 VLP can be produced by cloning the c-DNA (obtained from PCR) of the L1 capsid protein (HPV 16) and by inserting it into a yeast expression vector YEGa-HIR525 (under the control of GAL10 promoter). The modified expression vector YEGa-HPV16 L1 is then transformed and expressed in an expression system- Saccharomyces cerevisiae Y2805, since it is safe and it efficiently yields high level of recombinant proteins. Using Western Blot Analysis, the recombinant yeasts expressing high levels of the L1 capsid proteins are selected. Purification of the HPV 16 L1 VLP is performed by ultra-centrifugation and gel filtration.
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Similarly, the HPV 18

L1 VLP too can be produced following the procedure for HPV 16 L1 VLP . 6

Currently, there are two U.S FDA approved vaccines- Gardasil (Merck and Co.) and Cervarix (GlaxoSmithKline) that helps prevent infections from certain types of HPV. Gardasil is a quadrivalent vaccine, providing protection against 4 HPV types- 6,11,16 and 18 whereas Cervarix is a bivalent vaccine, providing protection against 2 HPV types- 6 and 11. 1 Both the HPV vaccines market is for girls and young women aged between 9 to 26 years. One difference between the two vaccines is that the Gardasil vaccine helps protect women from cervical cancer (HPV 16 and 18) and genital warts (HPV 6 and 11). Another characteristic feature of Merck and Co.s product is that it can be administered in males, since it provides protection against the HPV-6 and 11 (this is especially helpful for gay men who have sex with other men). In Gardasil, the recombinant HPV L1 major capsid proteins (Type 6,11,16 and 18) are synthesized independently, using the Saccharomyces cerevisiae expression system. The cells are then harvested and disrupted and the VLP L1 proteins, which assemble by themselves, undergo the process of purification via chromatography.
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To boost the ability of an antigen to stimulate an

immune response, an adjuvant is used in the preparation of the vaccine. Merck and Co. uses a preformed aluminum-containing adjuvant (amorphous aluminum hydroxyphosphate sulfate), which adsorbs the VLP. 8 The use of the HPV vaccine against cervical cancer is limited only to girls and younger women. Merck and Co. is making attempts to expand the age barrier from 9-26 years to 27 45 years. Clinical studies have been conducted and results have shown that the Gardasil is effective in older women too. However, the U.S FDA has not yet approved the proposal, citing the lack of long-term data. 9 The HPV vaccine was involved in several controversies in the U.S. Firstly, the high cost (for three doses of the Gardasil vaccine, the bill is $ 360), which is not affordable by all families. The vaccine also received strong opposition from health insurance companies to cover the high cost. Secondly, religious and conservative groups opposed to making vaccination with HPV vaccine compulsory, citing the reason as violation of parental rights. Finally, these groups felt that young girls vaccinated would be under the wrong impression of being immunized against the sexually transmitted disease and therefore may indulge in early sexual activities. 10

REFERENCES 1. 2. 3. 4. 5. 6. http://www.cancer.gov/cancertopics/factsheet/Prevention/HPV-vaccine http://www.jci.org/articles/view/28607 http://www.cdc.gov/vaccines/vpd-vac/hpv/vac-faqs.htm Development of Prophylactic HPV Vaccines- Lutz Gissmann and Martin Mueller www.msk.or.kr/jsp/downloadPDF1.jsp?fileName=404-13.pdf http://resources.metapress.com/pdfpreview.axd?code=542375mm1jg18j25&size=largest 7. http://www.drstaiger.com/sitebuildercontent/sitebuilderfiles/protheroarticle.pdf 8. http://www.rxlist.com/gardasil-drug.htm 9. http://health.usnews.com/health-news/blogs/on-women/2010/02/17/gardasil-protectsolder-women-gay-men 10. http://en.wikipedia.org/wiki/HPV_vaccine#Opposition_in_the_United_States