Safety and Persistent Immunogenicity of a Quadrivalent Human Papillomavirus Types 6, 11, 16, 18 L1 Virus-Like Particle Vaccine in Preadolescents and Adolescents: A Randomized Controlled Trial

Department of Pediatrics, Phramongkutklao Hostpital, Krung Thep, Bangkok, Thailand
The Pediatric Infectious Disease Journal (Impact Factor: 2.72). 04/2007; 26(3):201-9. DOI: 10.1097/01.inf.0000253970.29190.5a
Source: PubMed


Administration of a quadrivalent HPV-6/ 1/16/18 vaccine to 16- to 26-year-old women was highly effective in preventing HPV-6/ 1/16/18-related cervical/vulvar/vaginal precancerous lesions and genital warts. As the risk of acquiring HPV significantly rises after sexual debut, HPV vaccines should have the greatest benefit in sexually naive adolescents. We evaluated the tolerability and immunogenicity of quadrivalent vaccine in males and females 9 to 15 years of age through 18 months postenrollment.
In this randomized, double-blind trial, 1781 sexually naive children were assigned (2:1) to quadrivalent HPV-6/11/16/18 vaccine or saline placebo administered at day 1 and months 2 and 6. Serum neutralizing anti-HPV-6/11/16/18 responses were summarized as geometric mean titers (GMTs) and seroconversion rates. Primary analyses were done per-protocol (subjects received 3 doses, had no major protocol violations and were HPV type-specific seronegative at day 1). Adverse experiences were collected by diary card.
At month 7, seroconversion rates were > or =99.5% for the 4 vaccine-HPV-types. GMTs and seroconversion rates in boys were noninferior to those in girls (P < 0.001). At month 18, > or =91.5% of vaccine recipients were seropositive, regardless of gender. A higher proportion of vaccine recipients (75.3%) than placebo recipients (50.0%) reported one or more injection-site adverse experiences following any vaccination. Rates of fever were similar between vaccination groups. No serious vaccine-related adverse experiences were reported.
In 9- to 15-year-old adolescents, the quadrivalent vaccine was generally well tolerated and induced persistent anti-HPV serologic responses in the majority of subjects for at least 12 months following completion of a three-dose regimen. The vaccine durability supports universal HPV vaccination programs in adolescents to reduce the burden of clinical HPV disease, particularly cervical cancer and precancers.

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    • "These two vaccines have proven to be successful as prophylactic bivalent (Harper et al., 2006) and quadrivalent (FUTURE II Study Group, 2007) vaccines in women. In largely randomised clinical trials (Joura et al., 2008; Reisinger et al., 2007), they have been shown to elicit virus-neutralising antibodies at much higher concentrations than after natural infections. These vaccines are produced in eukaryotic cells through the expression of L1, which self-assembles as empty virus-like particles (VLPs) (Palmer et al., 2009) that are ultrastructurally and antigenically similar to the native virions. "
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    ABSTRACT: Human papilloma virus (HPV)-16 is the prevalent genotype associated with cervical tumours. Virus-like-particle-based vaccines have proven to be effective in limiting new infections of high-risk HPVs, but their high cost has hampered their use, especially in the poor developing countries. Avipox-based recombinants are replication-restricted to avian species and represent efficient and safe vectors also for immunocompromised hosts, as they can elicit a complete immune response. A new fowlpox virus recombinant encoding HPV-L1 (FPL1) was engineered and evaluated side-by-side with a FP recombinant co-expressing L1 and green fluorescent protein (FPL1GFP) for correct expression of L1 in vitro in different cell lines, as confirmed by Western blotting, immunofluorescence, real-time PCR, and electron microscopy. Mice were also immunised to determine its immunogenicity. Here, we demonstrate that the FPL1 recombinant better expresses L1 in the absence of GFP, correctly assembles structured capsomers into virus-like particles (VLPs), and elicits an immune response in a preclinical animal model. To our knowledge, this is the first report of HPV VLPs assembled in eukaryotic cells using an avipox recombinant. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Feb 2015 · Antiviral Research
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    • "Efficacy was highest in women before initiation of sexual intercourse and decreased significantly when viewed in population already exposed (Harper et al., 2006, Villa et al., 2006, Olsson et al., 2007). Two studies of quadrivalent vaccine, proven to be immunogenic and safe in adolescent girls and boys (Reisinger et al., 2007, Block et al., 2006). The antibody response of boys and girls aged 9-14 years on average two times that of 15-26 years young girls and women. "
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    ABSTRACT: Incidences of different types of cancer are increasing in Pakistan, among which cancer of Cervix and Respiratory pappilomatosis are of great concern because of their association with human Pappilomavirus (HPV). Cervical cancers typically distress women of middle age or older; however it may affect women in any age after the puberty. Two serotypes of HPV (16 & 18) accounts 70% of cervical cancer cases, while HPV (6 & 11) are considered low-risk viruses associated with genital warts (Condyloma acuminata) and Respiratory pappilomatosis in both gender. Generally, there is transient role of HPV in human body and are removed by immune system in or around 1 year. Data from different Pakistani hospitals provides sound evidence for increasing trends of cervical cancer, which is, being developing country imperative for us. As the cost of cancer management is increasing day by day with poor survival rate and its burden is borne by patient, their family or society in-large, so if screening or prevention is possible then there would be need to identify target population for screening and vaccination. By quality adjusted life year (QALY) measurement, the data from different sources indicates that adolescent age is the appropriate target population and is cost effective for vaccination. Two vaccines manufactured by recombinant DNA technology are licensed in some parts of the world for prevention of HPV related cancers, however both have certain advantage over another, as one of the vaccines contains viral like proteins of two HPV serotypes 16 & 18 and provide additional cross protection against HPV type 13 and 45 with 100% seroprotection, while the other vaccine, being quadrivalent offers protection against four serotypes 6, 11, 16 and 18. Both vaccines tolerability and safety profiles are similar and acceptable, however bivalent vaccine appears to provide long-lasting immunity by the development of memory B-cells hypothetically due to difference of adsorbing agent used by manufacturer, on the other hand, quadrivalent vaccine offers protection against cervical cancer but also offers additional protection against Condyloma acuminata and respiratory Pappilomatosis. As these vaccines are new in the market and initial trials indicate availability of antibodies for up to around 5 years i.e. why it is controversial at the moment that whether booster dose is recommended or not, however it is assumed that, there is no harm to have booster dose at 5th year of vaccination.
    Full-text · Article · Oct 2012 · Pakistan journal of pharmaceutical sciences
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    • "Prevention of infectious diseases comparable to HPV with vaccines is based on producing herd immunity through a sufficient coverage in susceptible individuals to reduce transmission [87]. The quadrivalent HPV vaccine is proven efficacious in males, likely prevents HPV transmission [88], and has been shown to reduce HPV 6/11-associated disease burden. Vaccinating males is currently not recommended by the WHO, but the impact of herd immunity on female cancers and other HPV-related cancers may need to be reconsidered [89, 90]. "
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    ABSTRACT: Cervical cancer and other human papillomavirus- (HPV-) related cancers are preventable, but preventive measures implemented in developing countries and especially in low-income rural regions have not been effective. Cervical cancer burden derived from sexually transmitted HPV infections is the heaviest in developing countries, and a dramatic increase in the number of cervical cancer cases is predicted, if no intervention is implemented in the near future. HPV vaccines offer an efficient way to prevent related cancers. Recently implemented school-based HPV vaccination demonstration programmes can help tackle the challenges linked with vaccine coverage, and access to vaccination and health services, but prevention strategies need to be modified according to regional characteristics. In urban regions WHO-recommended vaccination strategies might be enough to significantly reduce HPV-related disease burden, but in the rural regions additional vaccination strategies, vaccinating both sexes rather than only females when school attendance is the highest and applying a two-dose regime, need to be considered. From the point of view of both public health and ethics identification of the most effective prevention strategies is pivotal, especially when access to health services is limited. Considering cost-effectiveness versus justice further research on optional vaccination strategies is warranted.
    Full-text · Article · Jul 2011 · Infectious Diseases in Obstetrics and Gynecology
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