Elsevier

Vaccine

Volume 24, Supplement 1, 30 March 2006, Pages S16-S22
Vaccine

Immune responses to human papillomavirus

https://doi.org/10.1016/j.vaccine.2005.09.002Get rights and content

Abstract

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.

Section snippets

Introduction to host immunity

The world is a dangerous place in which Homo sapiens must continuously utilize sophisticated, flexible, and lethal defenses to rebuff the massed regiments of viruses, bacteria, and eukaryotic parasites. Host defense is a partnership between innate immunity (phagocytes, soluble proteins [e.g., cytokines, complement, and epithelial barriers]) and adaptive immunity (antibody, cytotoxic effector cells). The innate immune system detects the pathogen and acts as the first line of defense, clearing

The infectious cycle

The papillomaviruses are ubiquitous infectious agents that are characterized by strict species specificity and tissue tropism. The infectious cycle of these viruses is tailored to the differentiation program of the target cell. Different phases of permissive viral growth accompany the maturation of the keratinocyte as it progresses up the epithelium to become a terminally differentiated squame (Fig. 1). Infection and vegetative viral growth are absolutely dependent upon a complete program of

Immune intervention in HPV infections

Despite HPV's ability to impede host defenses, a successful immune response to genital HPV infections is established in most cases. This seems to be characterized by strong, local, cell-mediated immunity that is associated with lesion regression and the generation of serum neutralizing antibody. Such antibody is generated in most, but not all, infected individuals [34], [35], [36], and is directed against conformational epitope(s) on the L1 protein displayed on the outer surface of the intact

Summary

HPV infection of the genital tract is common in young sexually active individuals, the majority of whom clear the infection without overt clinical disease. Most of those who develop benign lesions eventually mount an effective cell-mediated immune response that results in lesion regression. Regression of anogenital warts is accompanied histologically by a CD4+ T cell-dominated Th1 response, and data from animal models suggest that the response is modulated by CD4+ T cell-dependent mechanisms.

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