PubMed Health⌕ Search

Biomedical subjects

Margaret Stanley

Publications and source records attributed to Margaret Stanley.

7 recordsLinked to original sources
PubMed2006

Chapter 12: Prophylactic HPV vaccines: underlying mechanisms.

Human papillomavirus virus-like particles (HPV VLP) can be generated by the synthesis and self-assembly in vitro of the major virus capsid protein L1. HPV L1 VLPs are morphologically and antigenically almost identical to native virions, and this technology has been exploited to produce HPV L1 VLP subunit vaccines. The vaccines elicit high titres of anti-L1 VLP antibodies that persist at levels 10 times that of natural infections for at least 48 months. At present the assumption is that the protection achieved by these vaccines against incident HPV infection and HPV-associated ano-genital pathology is mediated via serum neutralising Immunoglobulin G (IgG). However, since there have been very few vaccine failures thus far, immune correlates of protection have not been established. The available evidence is that the immunodominant neutralising antibodies generated by L1 VLPs are type-specific and are not cross-neutralising, although highly homologous HPV pairs share minor cross-neutralisation epitopes. Important issues remaining to be addressed include the duration of protection and genotype replacement.

Antibodies, Viral↗
PubMed2006

Immune responses to human papillomavirus.

The immune system uses innate and adaptive immunity to recognize and combat foreign agents that invade the body, but these methods are sometimes ineffective against human papillomavirus (HPV). HPV has several mechanisms for avoiding the immune system. HPV infects, and multiplies in keratinocytes, which are distant from immune centers and have a naturally short lifespan. The naturally short life cycle of the keratinocyte circumvents the need for the virus to destroy the cell, which would trigger inflammation and immune response. In addition, HPV downregulates the expression of interferon genes. Despite viral immune evasion, the immune system effectively repels most HPV infections, and is associated with strong localized cell mediated immune responses. New prophylactic L1 virus-like protein vaccines for HPV 16 and 18 and HPV 6, 11, 16, and 18 are in phase 3 trials. Available data suggests that these vaccines are safe, produce high levels of antibodies, and are effective at preventing HPV infection.

Antibodies, Viral↗
PubMed2005

HPV vaccines.

The ability to generate human papillomavirus virus (HPV)-like particles by the synthesis and self-assembly in vitro of the major virus capsid protein L1 has transformed our prospects for preventing cervical carcinoma in women. These particles provide vaccines that are immunogenic and safe, and data from proof-of-principle efficacy trials strongly suggest that they will protect against persistent HPV infection and cervical intraepithelial neoplasia. However, the duration of protection provided by these vaccines is not known, the antibody responses induced are HPV-type-specific and immunisation must occur pre-exposure to the virus. Second-generation vaccines could include an early antigen for protection post exposure and alternative delivery systems might be needed for the developing world. Therapeutic vaccines for low-grade intraepithelial disease are realistic but high-grade disease presents major hurdles for immunotherapies.

Cancer Vaccines↗
PubMed2003

Chapter 17: Genital human papillomavirus infections--current and prospective therapies.

Many therapies are available for the treatment of human papillomavirus (HPV)-associated disease, particularly external genital warts. However, at present, these therapies aim to remove the lesion rather than specifically target HPV infection. When disease and infection are local, as in cervical intraepithelial neoplasia (CIN), excisional therapies removing lesion and transformation-susceptible cells are highly effective. However, when infection is regional, as is usually the case for the anogenital warts, vulval intraepithelial neoplasia (VIN), anal intraepithelial neoplasia (AIN), penile intraepithelial neoplasia, and vaginal intraepithelial neoplasia, then current treatments are generally inadequate, with high recurrence rates. Future therapies will be directly or indirectly antiviral, targeting HPV protein functions or enhancing the ability of the immune system to resolve infection or inducing apoptosis indirectly in HPV-infected cells. In the short to the medium term, immunotherapies for low-grade disease are the most likely to be in the clinic. Vaccines targeting the E1 and E2 early proteins combined with immunomodulators or conventional adjuvants that induce a strong cell-mediated HPV antigen-specific response and good immune memory would be the predicted combination. Vaccines designed to target high-grade intraepithelial disease, even when used in combination with immunomodulators, are unlikely to effect lesion clearance in more than a fraction of the cases. However, they may have a role as adjunct therapy after cervical conization to prevent the recurrence of CIN or HPV reinfection. They certainly appear to have a role in multifocal disease, such as VIN and AIN, where partial clearance may be effected and lesion size reduced enough for effective ablative or excisional therapy. It seems unlikely that anti-HPV chemotherapies specifically targeting HPV protein functions will be in the clinic in the medium term. However, agents such as indole-3-carbinol have shown efficacy in small clinical trials, and if these effects are confirmed in larger, randomized, placebo-controlled trials, they could be clinically useful.

Adjuvants, Immunologic↗