Currently Approved Prophylactic HPV Vaccines

Diane M Harper

Disclosures

Expert Rev Vaccines. 2009;8(12):1663-1679. 

In This Article

The Two Vaccines

The two HPV vaccines, Cervarix® (GlaxoSmithKline, Middlesex, UK) and Gardasil® (Silgard®; Merck & Co., Inc., NJ, USA), contain a protein mimic of the L1 outermost protein capsid (VLPs) specific to the two most common HPV types causing cervical cancer, HPV-16 and -18 (Table 1). Gardasil also includes the VLPs for HPV-6 and -11, the most common HPV types causing genital warts. Along with the HPV type-specific VLPs, which direct the antibody response, the vaccines contain an adjuvant whose dual purpose is to prolong the immune response for as long as possible with the smallest amount of antigen (VLP) possible.

The primary mechanism of action of the prophylactic vaccines is the anti-HPV L1 humoral response,[12] which has been proven in animal studies to prevent acquisition and disease in unvaccinated animals after a viral challenge. Therefore, one of the goals of the prophylactic vaccines is to induce a robust antibody response that can only be achieved by combining the antigen with an adjuvant.

The adjuvant systems are different for each vaccine. Gardasil's system is based on the traditional general adjuvant principles while Cervarix's system is based on an adjuvant hypothesized to be targeted to the specific receptors for HPV infection. Cervarix contains monophosphoryl lipid A, a mimic of Toll-like receptor 4, which is hypothesized to function as a link between viruses, such as HPV, and the activation of the innate immune system. Having primed the innate immune system, the antigen-presenting cells stimulate the adaptive immune response by activating T cells, then B cells. The B cells proliferate into plasma cells, immediately making large quantities of antibody, and into memory B cells, which, upon later stimulation, can reactivate the plasma cells to replenish the neutralizing antibodies. This adjuvant system is called the AS04 adjuvant system. The AS04 system provides higher titers of antibodies than an aluminum adjuvant alone in humans, and the titers remain elevated above aluminium-induced antibody titers for at least 48 months.[13] The adjuvant system for Gardasil contains a proprietary aluminum hydroxyphosphate sulfate system which, in mice, provides more superior binding to HPV-16 than a simple aluminum adjuvant.[14] The results of the human trials for these two novel HPV vaccines provides early data upon which to design HPV-associated disease and cancer-prevention strategies.

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