Advances in human papilloma virus vaccines: a review (original) (raw)
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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
Vaccines against human papillomavirus: perspectives for controlling cervical cancer
Expert Review of Vaccines, 2007
Prophylactic vaccines against human papillomavirus (HPV) are on the market and will certainly reduce the incidence of genital warts and the risk of developing cervical cancer. In addition, they will contribute to reducing anal as well as head and neck cancers. However, effort should be made in the short term in order for these vaccines to have a real impact in the developing world, where almost 80% of cervical cancer cases occur. Since the available vaccines include only two of the HPV types found in cancers (approximately 70%), improvements in current mass screening programs -with the use of molecular techniques -must be made, particularly in developing countries. Therapeutic vaccines have been designed to control advanced lesions and residual illness and, although success has usually been obtained in animal models, clinical studies have not yet provided the anticipated results. Finally, the next generations of prophylactic HPV vaccines will probably include subunit vaccines, transgenic bacteria and plants, among others, and could represent useful and cheaper alternatives for reducing cervical cancer, particularly in the developing world.
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.
Progress in the development of a cervical cancer vaccine
Therapeutics and Clinical Risk Management, 2006
Persistent infection by 'high risk' genotypes of human papilloma virus (HPV) is necessary but not sufficient for the development of over 98% of cervical cancers. Thus the development of vaccines that prevent HPV transmission represent an important opportunity to prevent cervical cancer. There are several prophylactic HPV vaccine formulations based upon L1 virus-like particles (VLPs) currently in phase III trials and recently released data are extremely promising. However, many practical issues surrounding implementation of these vaccines need to be addressed including, who and when to vaccinate, duration of protection, and integration with current screening programs. The vaccines currently being evaluated target the two most prevalent high risk HPV types which are responsible for approximately 70% of cervical cancers. To increase the breadth of protection, it is likely that L1 VLPs of other viral subtypes must be included, although vaccines targeting the conserved regions of the L2 minor capsid protein warrant further exploration in this regard. In addition the vaccines nearing licensing will not combat established HPV-related disease and a therapeutic vaccine, of which there are several candidates in early stages of development, would be desirable. This review discusses the background to and progress in vaccine development and the issues surrounding the introduction of HPV vaccines.
Current Opinion in Chemical Biology, 2016
In 2006, the first human papillomavirus (HPV) virus-like particle (VLP) vaccine was licensed. Gardasil 1 , the quadrivalent HPV 6, 11, 16 and 18 recombinant VLP vaccine (4vHPV), developed by Merck demonstrated remarkable efficacy in prevention of important clinical precursors to cervical cancer and genital warts. The vaccine was designed to protect against HPV 16 and 18 that cause 70% of cervical cancers and HPV 6 and 11 that cause 90% of genital warts. Initially, Gardasil 1 was indicated in the United States for women 9-26 years of age for the prevention of HPV 16 and 18-related cervical, vulvar and vaginal cancer, HPV 6, 11, 16 and 18-related genital intraepithelial neoplasia and the prevention of HPV 6 and 11related genital warts. Subsequently, a bivalent HPV 16 and 18 VLP vaccine, Cervarix (2vHPV) developed by GlaxoSmithKline was licensed. Since the original licensures, the indications for Gardasil 1 have been expanded to include males and a vaccine with extended HPV coverage, Gardasil 9 (9vHPV), licensed in 2014.
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...
Development of New Human Papillomavirus Vaccines
Human Papillomavirus and Related Diseases - From Bench to Bedside - A Clinical Perspective, 2012
Persistent HPV infection is considered the principal causative agent of cervical and other anogenital cancers. The finding that HPV DNA is present in practically all cases of cervical www.intechopen.com
The Past, Today, and the Future of Human Papilloma Virus Vaccines
International Journal of Hematology and Oncology, 2011
Human papilloma virus (HPV) is the most common sexually transmitted viral infection. The clinical spectrum of disease ranges from asymptomatic infection, to benign warts (primarily caused by low-risk HPV genotypes 6 and 11) to invasive malignancy. Over 70% of cervical cancer associated with the high-risk genotypes 16 and 18. According to the GLOBOCAN 2002 investigation which is held by International Agency for Research on Cancer the cervical cancer incidence in Turkey is 4.5 in 100.000. It was seen 1364 new cervix cancer case and 726 deaths due to cancer in the same year. In Turkey, cervical cancer is the 9th most common cause of cancer death in women. This review will highlight the science behind HPV vaccines, recent advances in HPV prophylactic vaccine development, the most recent clinical trial results and important issues we need to consider prior to implementation of the vaccine in Turkey.
Developing an HPV vaccine to prevent cervical cancer and genital warts
Vaccine, 2007
The challenges of the journey from target identification through development of a prophylactic quadrivalent human papillomavirus (HPV) vaccine have been met in Gardasil ®. Cervical cancer is the second leading cause of cancer-related death in women worldwide. Approximately 70% of cervical cancer is caused by infection with HPV types 16 and 18 and ∼90% of genital warts are caused by HPV types 6 and 11. The quadrivalent HPV vaccine was generated by expression of the major capsid protein (L1) of HPV types 16, 18, 6 and 11 in yeast. L1 proteins self assemble into pentamer structures and these pentamer structures come together to form virus-like particles (VLPs). The VLPs are antigenically indistinguishable from HPV virions. The VLPs contain no viral DNA and therefore the vaccine is non-infectious. Gardasil ® is composed of VLPs of HPV types 16, 18, 6 and 11 conjugated to a proprietary amorphous aluminum hydroxyphosphate sulfate adjuvant. The results of a rigorous clinical program have demonstrated that the vaccine is safe and highly efficacious in preventing dysplasias, cervical intraepithelial neoplasias (CIN 1-3) the precursors of cervical cancer and external genital lesions caused by vaccine-HPV types. In conclusion, Gardasil ® addresses a major medical need, that is, reduction of HPV-related disease including cervical cancer as a safe, immunogenic, and highly efficacious vaccine.
Human papillomavirus and HPV vaccines: a review
Bulletin of the World Health Organization, 2007
Cervical cancer, the most common cancer affecting women in developing countries, is caused by persistent infection with "high-risk" genotypes of human papillomaviruses (HPV). The most common oncogenic HPV genotypes are 16 and 18, causing approximately 70% of all cervical cancers. Types 6 and 11 do not contribute to the incidence of high-grade dysplasias (precancerous lesions) or cervical cancer, but do cause laryngeal papillomas and most genital warts. HPV is highly transmissible, with peak incidence soon after the onset of sexual activity.