Broad-spectrum human papillomavirus vaccines: new horizons but one step at a time.

This issue of the Journal presents the results of an experimental project describing the technology and the model system to generate novel human papillomavirus (HPV) vaccines. Rather than using the immune capacity of the L1 capsid epitopes, these prototypes are based on the unique properties of the L2 protein of the capsid to induce broad-spectrum (BS) HPV antigenic recognition and the formation of neutralizing antibodies to a large number of HPV types. The results open the door to a novel family of second-generation HPV vaccines with substantial potential value in the public health horizon. The developments and the clinical program will still require years of investigation, but the concept addresses in a meaningful way some of the recognized limitations of current vaccines, including the continuous screening requirements and at least partially the diffi culties related to the current vaccine cost. There are currently two vaccines that have contributed phase III clinical trial results: Gardasil which targets two oncogenic HPV types (16 and 18) and two nononcogenic HPV types (6 and 11) responsible for genital warts and respiratory papillomatosis, and Cervarix (GlaxoSmithKline Biologicals, Rixensart, Belgium), which targets two oncogenic HPV types (16 and 18) and is formulated with a novel adjuvant ASO4. These vaccines are currently licensed in more than 120 countries and have been introduced into routine vaccination programs in many developed countries (1 – 3). More than 40 million doses have already been distributed. Most of the critical phase III results are available for Gardasil, and fi nal results of the pivotal trial with Cervarix will be available in 2009. These two vaccines have shown to date high effi cacy against the predefi ned endpoint lesions (cervical intraepithelial neoplasia of grade 2 or more [CIN 2+]), adequate safety and tol-erability profi les, high immunogenicity, long-term duration of protection in the range of 6 – 7 years, and strong indications of its ability to induce immune memory [reviewed in (3 – 5)]. The global estimates of the protection against cervical cancer of the currently available vaccines range from 70% attributed to HPV-16 and HPV-18 to 75% – 85% related to a relatively small geographical variation and to additional nonvaccine-type cross-protection. None of the vaccines have shown therapeutic activity. Some of the limitations of current vaccines are presented in Table 1. Also shown are areas that could be, at least theoretically, overcome by BS HPV vaccines (Table 1) (6 – 9). …