Vaccines for papillomavirus infection (original) (raw)

Papillomavirus-like particles and HPV vaccine development

Seminars in Cancer Biology, 1996

Human papillomavirus-like particles (VLPs), self-assembled after high level expression of the papillomavirus L1 virion capsid protein in non-mammalian cells, are attractive candidates for a subunit vaccine to prevent genital HPV infection and the subsequent development of cervical cancer. In animal studies, purified VLPs induce high titers of antibodies against conformational type specific L1 epitopes. These antibodies neutralize homologous virions in in-vitro assays and protect against experimental challenge in several animal models. The encouraging results in animals justify the initiation of human trials of HPV VLP-based vaccines. Factors to be considered when designing these trials are discussed.

Current Status of Human Papillomavirus Vaccines

Journal of the Formosan Medical Association, 2010

Cervical cancer is the second most prevalent cancer among women, accounting for 500,000 cases per year [1]. There have been continuous efforts to determine the causes of the onset of cervical cancer. Since 1977, when Zur Hausen [2] discovered that the infection of human papillomavirus (HPV) is the major causative agent of cervical cancer, various research has been conducted and is in progress. As a result, it has been determined that the relationship between cervical cancer and the HPV infection is higher than the relationship between lung cancer and smoking, and also higher than the relationship between liver cancer and the hepatitis B virus [3]. Globally, approximately 100 different types of HPV have been reported; types 16 and 18 have caused 70% of cervical cancer onsets worldwide [4-8]. A new vaccine was developed using the non-infective recombinant virus like particle (VLP) for the antigen of the vaccine. In 1991, Zhou et al. [9] developed VLP technology, which was the crucial opportunity to develop the cervical cancer vaccine. Seventy-two of the capsomers, each comprising five L1 proteins, are assembled into a VLP, and such VLP exhibits a virus-like structure; therefore, it has higher antigenicity while being safe due to the absence of foreign DNA [10]. Currently, there are two cervical cancer vaccines used glo bally on the market: quad

Prevention of cancer by prophylactic human papillomavirus vaccines

Current Opinion in Immunology, 2011

Oncogenic human papillomaviruses (HPV) are exclusively mucosal pathogens that are noncytopathic and the basal epithelial cells harboring and maintaining an infection do not produce either capsid antigen or virus. The efficacy of the licensed L1 virus-like particle (VLP) vaccines has encouraged development of several second generation vaccines aimed at expanding the coverage to all oncogenic HPV types and reducing barriers to global implementation. Currently there is no defined immune correlate of protection that can be used to determine if an individual patient is protected and for the evaluation of these second generation vaccines. Surprisingly, passive transfer of neutralizing serum antibody is protective in animal models. Recent studies suggest how neutralizing antibody mediates immunity against mucosal HPV and the possible impact of memory B cells.

Recombinant vaccines for the prevention of human papillomavirus infection and cervical cancer

Experimental and Molecular Pathology, 2009

Carcinogenic human papillomaviruses (HPVs) that cause cervical cancer preferentially infect basal, metaplastic squamous cells of the transformation zone. If infection persists, and a vegetative infection ensues, a premalignant lesion may develop with the potential to progress into an invasive squamous cell carcinoma. Papillomavirus prophylactic vaccines target the systemic immune system for induction of neutralizing antibodies that protect the basal cells against infection. Because the carcinogenic HPVs are susceptible to neutralization by antibodies for 9-48 h after reaching the basal cells, both low and high titered HPV type-specific antibodies induced by HPV L1 and L2-based vaccines are highly efficacious. The greatest burden of HPV-associated cancers occurs in poor areas of the world where women do not have access to routine gynecological care. The burden of HIV/AIDS in these same regions of the world has added to the burden of HPV-associated disease. There is an urgent need for a cost-effective, broad-spectrum HPV prophylactic vaccine in developing countries, which necessitates substantial cost subsidization of the virus-like particle (VLP) based vaccines licensed in industrialized countries or an alternative approach with second-generation vaccines that are specifically designed for delivery to women in resource-poor communities.

Therapeutic Human Papillomavirus Vaccines: A Review

International Journal of Pharmaceutical Sciences Review and Research

Human Papillomavirus (HPV) is the most common sexually transmitted disease which can infect different parts of the body including uterus. Cervical cancer is the second most common cancer among women worldwide. The HPV-related disease appears to be increasing but treatment is limited, difficult and insufficient with high relapse rate. This growth in disease burden had made the development of two an effective prophylactic Human Papillomavirus vaccines namely Gardasil® - quadrivalent (Merck) and Cervarix™ - bivalent (GlaxoSmithKline). These vaccines are widely marketed internationally. However, pre-existing HPV infection is a highly prevalent in public health of developed and developing countries. According to published literature, antigen-specific T cell- mediated immunity is required for treatment of established HPV infection. Therefore, it is an important to develop vaccines that induce cell-mediated immune responses which are specific for early viral proteins in order to effect reg...

The current state of therapeutic and T cell-based vaccines against human papillomaviruses

Immunotherapy Therapeutic vaccine T cell-based vaccine HPV E6 HPV E7 abstract Human papillomavirus (HPV) is known to be a necessary factor for many gynecologic malignancies and is also associated with a subset of head and neck malignancies. This knowledge has created the opportunity to control these HPV-associated cancers through vaccination. However, despite the availability of prophylactic HPV vaccines, HPV infections remain extremely common worldwide. In addition, while prophylactic HPV vaccines have been effective in preventing infection, they are ineffective at clearing pre-existing HPV infections. Thus, there is an urgent need for therapeutic and T cell-based vaccines to treat existing HPV infections and HPV-associated lesions and cancers. Unlike prophylactic vaccines, which generate neutralizing antibodies, therapeutic, and T cell-based vaccines enhance cell-mediated immunity against HPV antigens. Our review will cover various therapeutic and T cell-based vaccines in development for the treatment of HPV-associated diseases. Furthermore, we review the strategies to enhance the efficacy of therapeutic vaccines and the latest clinical trials on therapeutic and T cell-based HPV vaccines.

Therapeutic Vaccines Against Human Papillomavirus and Cervical Cancer

The Open Virology Journal, 2009

Cervical cancer and its precursor intra-epithelial lesions are linked to infection by a subset of so-called "highrisk" human papillomavirus types, which are estimated to infect nearly four hundred million women worldwide. Two prophylactic vaccines have been commercialized recently targeting HPV16 and 18, the most prevalent viral types found in cervical cancer, which operate through induction of capsid-specific neutralizing antibodies. However, in patients with persistent infection these vaccines have not been found to protect against progression to neoplasia. Attempts are being made to develop therapeutic vaccines targeting nonstructural early viral proteins. Among these, E6 and E7 are the preferred targets, since they are essential for induction and maintenance of the malignant phenotype and are constitutively expressed by the transformed epithelial cells. Here are reviewed the most relevant potential vaccines based on HPV early antigens that have shown efficacy in preclinical models and that are being tested in clinical studies, which should determine their therapeutic capacity for eradicating HPV-induced premalignant and malignant lesions and cure cervical cancer.