Quadrivalent human papillomavirus recombinant vaccine: The first vaccine for cervical cancers

Abstract

Gardasil is the first quadrivalent human papillomavirus (HPV)-types 6, 11, 16, 18 recombinant vaccine approved by the FDA on June 8, 2006. It induces genotype-specific virus-neutralizing antibodies and prevents infection with HPV. Various clinical trials demonstrated a reduction in the incidence of vaccine-type-specific persistent infections and of associated moderate- and high-grade cervical dysplasias and carcinomas in situ after its use. Gardasil is currently approved by FDA for prevention of genital warts, cancers and precancerous conditions of cervix and vulva in 9-26 year old females. Three doses of 0.5 ml of gardasil each at 0, 2 and 6 months are given intramuscularly. It is contraindicated in individuals who are hypersensitive to the active substances or to any of the excipients of the vaccine, patients with bleeding abnormalities or patients on anticoagulant therapy and during pregnancy. However, the vaccine, at an estimated $300-500 per course, is too expensive for many women in developing countries. Moreover, question regarding the longevity of the protection by vaccine is still unsolved. Hence, longer studies are required to establish its real status in cancer prevention.

Vaccines for human papillomavirus infection: A critical analysis

“…[10] It has been observed that, when L1 and L2 proteins are expressed in vitro, they self-assemble into a structure identical to the viral capsid known as "virus-like particles" (VLP). [10,16,17] The VLP induces a humoral immune response similar to a live virion but does not produce infection in the recipient because it lacks viral nucleic acid. [2] Zhou et al led the way to prophylactic vaccine in 1991 by demonstrating that the HPV-16 L1 capsid proteins self-assembled into conformational VLP that resembled native virions in a recombinant system.…”

“…[29] GARDASIL GARDASIL Gardasil is the first quadrivalent HPV types 6,11,16,18 recombinant vaccine to be approved by the FDA on June 8, 2006. [16] It was prepared from the highly purified VLPs of the major capsid (L1) protein of HPV types 6,11,16,18 adsorbed on adjuvants. [16] Advisory Committee on Immunization Practices (ACIP) has recommended Gardasil for females aged 11 to 12 years, but it may be administered in females aged 9 to 26 years.…”

“…[16] It was prepared from the highly purified VLPs of the major capsid (L1) protein of HPV types 6,11,16,18 adsorbed on adjuvants. [16] Advisory Committee on Immunization Practices (ACIP) has recommended Gardasil for females aged 11 to 12 years, but it may be administered in females aged 9 to 26 years. [29] It is most effective when administered before initiation of sexual activity.…”

“…[2] More than 100 types of HPV have been identified, [1] 40 of which are associated with anogenital diseases in men and women. [2] On the basis of association with cervical cancers, 15 HPV types (16,18,31,33,35,39,45,51,52,56,58,59,68,73 and 82) were classified as high risk for cervical cancer, 3 as probable high risk (26,53,66) and 12 as low risk (6,11,40,42,43,44,54,61,70,72, 81 and CP6108). [3] HPV DNA is detected in 99% of cervical carcinomas [5] approximately 70% contain HPV types 16 or 18, [6] of which HPV 16 is the single most common high-risk HPV type causing anogenital cancer precursor lesions such as cervical intraepithelial neoplasia (CIN) and cervical cancers.…”

The growing impact of lyophilized cell-free protein expression systems

“…In addition to creating cancer vaccines, stockpiling of protein expression systems enables rapid vaccine production in response to a viral pandemic threat. 37 Shelf-stable protein expression may additionally impact dendritic cell immunotherapy techniques, 38 enable effective immunotherapy for combating warts, 39 and supply rapid purification-free production of vectors for gene delivery. 40,41 Biotherapeutics and vaccines in remote locations…”