Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial

Harper, Diane M.; Franco, Eduardo L.; Wheeler, Cosette M.; Ferris, Daron G.; Jenkins, David; Schuind, Anne; Zahaf, Toufik; Innis, Bruce L.; Naud, Paulo; Carvalho, Newton Sérgio de; Roteli-Martins, Cecília Maria; Teixeira, Júlio César; Blatter, Mark M.; Korn, Abner P.; Quint, Wim; Dubin, Gary

doi:10.1016/s0140-6736(04)17398-4

Cited by 1,428 publications

(917 citation statements)

References 34 publications

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“…5 years follow-up, both ATP and intention-to-treat (ITT) analyses showed high efficacy of the bivalent vaccine against both incident and persistent HPV 16 and 18 infections, even with use of vaginal self-sampling, the most sensitive method for HPV detection [50]. In the ITT analysis, vaccine efficacy was 95 .…”

Section: Primary Prevention : Prophylactic Vaccinesmentioning

confidence: 94%

Vaccines for cervical cancer

Lowndes¹

2006

Epidemiol. Infect.

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SUMMARYThis review focuses on current and future prevention of invasive cervical cancer (ICC), the second most common cancer among women worldwide. Implementation of population-based cytological screening programmes, using the 'Pap ' smear to detect pre-cancerous lesions in the cervix, has resulted in substantial declines in mortality and morbidity from ICC in North America and some European countries. However, cases of, and deaths from, ICC continue to occur. Primary prevention of infection with high-risk human papillomavirus (HPV) types, the central causal factor of ICC, could further reduce incidence of and mortality from ICC. This is particularly the case in developing countries, which bear 80% of the burden of ICC, and where effective Pap screening programmes are extremely difficult to implement. Very promising results from several trials of synthetic HPV type-specific monovalent (HPV 16) and bivalent (HPV 16 and 18) vaccines have recently been published, showing high efficacy against type-specific persistent HPV infection and development of type-specific pre-cancerous lesions. Large-scale phase III trials of a number of such vaccine candidates are currently underway, and there is real hope that an effective vaccine capable of protecting against infection with HPV types 16 and 18 (which together account for y70% of cervical cancer cases worldwide), and thereby of preventing development of a very significant proportion of cases of ICC, could be available within the next 2 years.

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Section: Primary Prevention : Prophylactic Vaccinesmentioning

confidence: 94%

Vaccines for cervical cancer

Lowndes¹

2006

Epidemiol. Infect.

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“…Recent clinical trials have shown that VLP afford excellent protection against persistent infection [20,21]. Because of the lack of a suitable cell culture system for in vitro propagation of HPV and the unavailability of virions, HPV VLP have been used as soluble surrogates for native virus particles.…”

Section: Introductionmentioning

confidence: 99%

Role of DC‐SIGN in the activation of dendritic cells by HPV‐16 L1 virus‐like particle vaccine

et al. 2006

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Dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN), a specific C-type lectin expressed on DC, binds and transmits different pathogens to susceptible cells. In the present study, we examined the role of DC-SIGN in the capture of human papillomavirus (HPV) pseudovirions and activation of DC. We demonstrate that HPV virus-like particles (VLP) bind to DC-SIGN expressed on transfected Raji cells and that antibodies against DC-SIGN block this interaction. DC take up VLP, which activate expression of costimulatory markers and cytokines/ chemokines. Although our results indicate that DC-SIGN is not the major receptor for VLP in DC, this interaction contributes to the activation of DC surface antigens (HLA class I) and of various cytokines/chemokines, particularly TNF-a, IL-6, and RANTES. Induction of these markers in DC by VLP was significantly abrogated when binding to DC-SIGN was blocked by anti-DC-SIGN antibodies. These results suggest that DC-SIGN has a functional role in DC activation induced by HPV-16 L1-VLP, and thus highlight new aspects of DC interactions with HPV VLP. IntroductionThe C-type lectin dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN; CD209) is a pathogen recognition receptor that interacts with mannose residues of glycoproteins in a calciumdependent manner via its C-terminal carbohydrate recognition domain [1,2]. DC-SIGN acts both as an adhesion molecule and pathogen recognition receptor, facilitating DC binding and internalization of several viruses, including HIV-1 [3].In addition to HIV, DC-SIGN was recently shown to bind a variety of microorganisms such as CMV [4], Ebola virus [5], Dengue virus [6], hepatitis C virus [7,8], simian immunodeficiency virus [9], Leishmania [10], Candida albicans [11], Mycobacterium [12][13][14] and Schistosoma [15]. Some pathogens subvert DC functions to escape immune surveillance [16]. DC-SIGN is abundantly expressed primarily on DC, including those derived from monocytes and those located beneath the genital surface [3].Human papillomavirus (HPV) virus-like particles (VLP) are a promising vaccine candidate for HPV and cervical cancer [17][18][19][20]. Recent clinical trials have shown that VLP afford excellent protection against persistent infection [20,21]. Because of the lack of a suitable cell culture system for in vitro propagation of HPV and the unavailability of virions, HPV VLP have been used as soluble surrogates for native virus particles. The routes of HPV-16 L1-VLP entry in DC and the nature of cellular receptors involved in capture have been studied but remain to be fully characterized. HPV VLP Here, we report that HPV-16 L1-VLP particles bind to DC-SIGN in transfected cell lines, and to a lesser extent in DC, and that this interaction participates in L1-VLPinduced activation of DC. Thus, DC-SIGN is likely involved in DC activation by HPV VLP. Results and discussion HPV L1-VLP bind to DC-SIGN in DC-SIGN-transfected cell linesTo study interactions between L1-VLP and DC-SIGN, we...

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“…Nonetheless, some women in the population for whom the vaccines are approved will have been exposed to vaccine HPV types through sexual activity before vaccination. 5,6 Though there have been extensive data published on the efficacy of both vaccines, [7][8][9][10][11][12][13][14][15] less is known about the impact of HPV vaccination in women with ongoing HPV16 or 18 infections. Adequate knowledge of the HPV vaccines' impact on such women has important clinical implications, particularly with respect to HPV16 and HPV18, as several studies have shown that women who are persistently or chronically infected with cervical HPV16 or HPV18 are at considerably higher risk for developing high grade cervical lesions and cancer, compared with women positive for non-HPV16/18 oncogenic types, oncogenic HPV-negative women, or those transiently infected with HPV16/18.…”

mentioning

confidence: 99%

Impact of an HPV6/11/16/18 L1 virus‐like particle vaccine on progression to cervical intraepithelial neoplasia in seropositive women with HPV16/18 infection

Haupt¹,

Wheeler²,

Brown

et al. 2011

Intl Journal of Cancer

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The impact of a human papillomavirus (HPV) vaccine on development of cervical intraepithelial neoplasia grade 2‐3 or adenocarcinoma in situ (CIN2‐3/AIS) in women with ongoing HPV16 or 18 infections prevaccination is reported. Seventeen thousand six‐hundred and twenty‐two women aged 16–26 were enrolled in 1 of 2 randomized, placebo‐controlled, efficacy trials (Protocols 013 and 015). Vaccine or placebo was given at day 1, month 2 and 6. Women were tested for HPV6/11/16/18 DNA and antibodies at day 1. We focus on the subset of women who were seropositive and DNA positive to HPV16 or HPV18 prevaccination. Incidence is expressed as the number of women with an endpoint per 100 person‐years‐at‐risk. In total, 419 vaccine and 446 placebo recipients were both seropositive and DNA positive to HPV16 or HPV18 prevaccination and had at least one follow‐up visit. In Protocol 013, the incidence of HPV16/18‐related CIN2‐3/AIS among these women was 10.9 in the vaccine arm and 7.0 in the placebo arm (vaccine efficacy = −54.9; 95% CI: −181.7, 13.0). In Protocol 015, the incidence of HPV16/18‐related CIN2‐3/AIS was 5.5 in the vaccine arm and 6.2 in the placebo arm (vaccine efficacy = 12.2%; 95% CI: −29.8, 40.9). These data suggest HPV vaccination neither reduces nor enhances progression to HPV16/18‐related high grade cervical lesions, and cervical cytology screening and corresponding management should continue as per local recommendations. Ultimately, population‐based surveillance of vaccinated individuals beyond these clinical trials will be required to further address questions regarding the impact of vaccination in women exposed to vaccine HPV types before vaccination.

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Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial

Cited by 1,428 publications

References 34 publications

Vaccines for cervical cancer

Vaccines for cervical cancer

Role of DC‐SIGN in the activation of dendritic cells by HPV‐16 L1 virus‐like particle vaccine

Impact of an HPV6/11/16/18 L1 virus‐like particle vaccine on progression to cervical intraepithelial neoplasia in seropositive women with HPV16/18 infection

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