L1-Specific Protection from Tumor Challenge Elicited by HPV16 Virus-like Particles

Bruijn, Marloes L. H. De; Greenstone, Heather L.; Vermeulen, H.; Melief, Cornelis J.M.; Lowy, Douglas R.; Schiller, John T.; Kast, W. Martin

doi:10.1006/viro.1998.9372

Cited by 62 publications

(54 citation statements)

References 19 publications

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“…Therefore, neither infected basal keratinocytes nor cervical cancer cells express detectable levels of L1, and so are unlikely to be recognized by L1-specific cytotoxic T cells. However, a bystander effect or immune recognition of L1 levels below the level of experimental detection are possible 59,60 . For example, the vaccination of mice with HPV16 VLPs induces effective L1-specific CD8-dependent protection from challenge with an HPV16 genome-transformed murine tumour line that does not express levels of L1 protein detectable by western blot or immunofluorescence 59 .…”

Section: Other Outstanding Issues With Hpv Vaccines Do L1 Vlp Vaccinementioning

confidence: 99%

“…However, a bystander effect or immune recognition of L1 levels below the level of experimental detection are possible 59,60 . For example, the vaccination of mice with HPV16 VLPs induces effective L1-specific CD8-dependent protection from challenge with an HPV16 genome-transformed murine tumour line that does not express levels of L1 protein detectable by western blot or immunofluorescence 59 . Furthermore, patients with genital warts vaccinated with HPV6 L1 VLPs had more frequent clearance than historical controls, but this trial was not placebo controlled 61 .…”

Section: Other Outstanding Issues With Hpv Vaccines Do L1 Vlp Vaccinementioning

confidence: 99%

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How will HPV vaccines affect cervical cancer?

2006

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Cancer of the uterine cervix is the second largest cause of cancer deaths in women, and its toll is greatest in populations that lack screening programmes to detect precursor lesions. Persistent infection with 'high risk' genotypes of human papillomavirus (HPV) is necessary, although not sufficient, to cause cervical carcinoma. Therefore, HPV vaccination provides an opportunity to profoundly affect cervical cancer incidence worldwide. A recently licensed HPV subunit vaccine protects women from a high proportion of precursor lesions of cervical carcinoma and most genital warts. Here we examine the ramifications and remaining questions that surround preventive HPV vaccines.Epidemiological and laboratory studies overwhelmingly support a necessary role for persistent human papillomavirus (HPV) infection and transcription in cervical carcinogenesis 1,2 (BOX 1). Importantly, HPV infection alone is not sufficient for cervical carcinogenesis, and additional steps occur over one or two decades. HPV is probably the most common sexually transmitted disease. It is estimated that the worldwide agestandardized prevalence of current HPV infection is 10.5% (95% CI 9.9-11.0) of women; the prevalence varies about 20-fold between different regions, from 1.4% (95% CI 0.5-2.2) in Spain to , although adenocarcinomas of the cervix are more challenging to detect with this approach. Progression to cancer can usually be prevented by the ablation or surgical removal of high-grade precursor lesions (HSIL or CIN2/3). In 2005, more than 60 million Pap smears were performed in the United States, and it is estimated that such screening programmes and intervention have reduced the incidence of cervical cancer by ~80% in the United States, but at a cost of more than US$6 billion a year.Despite this success, many women do not have access to screening. This problem is most acute in disadvantaged minorities in developed nations, in cultures that do not accept the screening process and in countries that are remote and lack the resources for screening programmes. Consequently, the impact of cervical cancer is greatest in these countries; the latest global estimates (from 2002) are 493,000 new cervical cancer cases each year, and 274,000 deaths, 80% of which occur in developing countries 8 .Vaccination traditionally represents the most cost-effective approach to combat infectious disease. Two approaches to vaccination, or a combination of both, can be considered: prophylactic (preventive) and therapeutic immunization. Prophylactic vaccination of healthy individuals against the aetiological agent protects against acquisition of the disease, but confers some risk to otherwise healthy patients and requires massive programmes to vaccinate a significant fraction of the population. Comprehensive prophylactic vaccination has historically proven most successful in disease reduction. The US Food and Drug Administration (FDA) approved a preventive HPV vaccine on 8 June 2006 for the immunization of women between 9-26 years of age 9 , and a second vacci...

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Section: Other Outstanding Issues With Hpv Vaccines Do L1 Vlp Vaccinementioning

confidence: 99%

Section: Other Outstanding Issues With Hpv Vaccines Do L1 Vlp Vaccinementioning

confidence: 99%

How will HPV vaccines affect cervical cancer?

2006

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“…The highly ordered, close-packed xenogeneic structure of HPV16 L1 VLP induces both high titer protective Ab (23)(24)(25) and potent cell-mediated immune responses (26). Indeed, i.m.…”

Section: B Lymphocyte Activation By Human Papillomavirus-like Particlmentioning

confidence: 99%

B Lymphocyte Activation by Human Papillomavirus-Like Particles Directly Induces Ig Class Switch Recombination via TLR4-MyD88

Yang¹,

Murillo²,

Delannoy³

et al. 2005

The Journal of Immunology

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Vaccination with human papillomavirus type 16 (HPV16) L1 virus-like particles (VLP) induces both high titer neutralizing IgG and protective immunity. Because protection from experimental infection by papillomavirus is mediated by neutralizing IgG, we sought the mechanisms that trigger humoral immunity to HPV16 L1 VLP. We find that HPV16 L1 VLP bind to murine B lymphocytes thereby inducing activation-induced cytidine deaminase expression and Ig class switch recombination to cause the generation of IgG. HPV16 L1 VLP also activate production of proinflammatory factors IFN-α, IL-6, MIP-1α, RANTES, and KC, up-regulate the expression of costimulatory molecules by naive B cells, and increase the B1 B cell subpopulation. These B cell responses to HPV16 L1 VLP are dependent upon MyD88. Although MyD88−/− B cells produce only μ transcript after exposure to HPV16 L1 VLP, MyD88+/+ B cells express α, γ, and μ Ig H chain and activation-induced cytidine deaminase transcripts. Notably, TLR4 mutant C3H/HeJ mice exhibited significantly reduced HPV16 VLP-specific IgG1, IgG2a, IgG2b, and IgG3 titers after vaccination as compared with the control C3H/HeOuJ mice. HPV16 L1 VLP directly activated class switch recombination and costimulatory molecule expression by B cells of C3H/HeOuJ mice but not C3H/HeJ mice. Thus HPV16 L1 VLP directly activate B cells to induce CD4+ T cell independent humoral immune responses via TLR4- and MyD88-dependent signaling.

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“…The number of spots generated against each antigen was calculated as the average number of spots per experiment minus the average number of spots per background wells. ELISPOT results are presented as spots per 10 6 PBMCs. Statistical methods.…”

Section: Vol 76 2002 Hpv-11-specific Immunity Primed By a Vlp-basedmentioning

confidence: 99%

“…When expressed in bacteria or eukaryotic cells, the papillomavirus capsid protein L1, alone or in combination with L2, autoassembles to form intact VLPs that morphologically and antigenically resemble native virion (17). Immunization of animals with various papillomavirus VLP-based vaccines has been shown to elicit high antibody titer (4,22,23,27,32,52) and durable T-cell responses (10,31,37,40). The presence of vaccine-induced neutralizing antibodies was shown to correlate with complete protection against viral challenge in the cottontail rabbit papillomavirus rabbit model (4, 22), the canine oral papillomavirus dog model (52), and the bovine papillomavirus (BPV) cow model (23,27).…”

mentioning

confidence: 99%

Priming of Human Papillomavirus Type 11-Specific Humoral and Cellular Immune Responses in College-Aged Women with a Virus-Like Particle Vaccine

Emeny

Wheeler

Jansen³

et al. 2002

J Virol

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In this study, we evaluated the potency of a human papillomavirus (HPV) virus-like particle (VLP)-based vaccine at generating HPV type 11 (HPV-11)-specific cellular and humoral immune responses in seronegative women. The vaccine was administered by intramuscular immunizations at months 0, 2, and 6. A fourth immunization was administered to approximately half of the women at month 12. All vaccine recipients had positive HPV-11 VLP-specific lymphoproliferative responses at month 3 following the second immunization (geometric mean lymphoproliferative stimulation index [SI] ‫؍‬ 28.4; 95% confidence interval [CI] ‫؍‬ 16.9 to 48.0) and HPV-11 VLP-specific antibody titers following the first immunization at month 1 (geometric mean antibody titer ‫؍‬ 53.9 milli-Merck units/ml, 95% CI, 34.8 to 83.7). In contrast, lymphoproliferative and antibody titer responses were never detected in the participants who received placebo. Relatively homogeneous lymphoproliferative responses were observed in all vaccinated women. The mean lymphoproliferative SI of the vaccinated group over the first 12 months of the study was 7.6-fold greater than that of the placebo group following the initial immunization. The cellular immune responses generated by VLP immunization were both Th1 and Th2, since peripheral blood mononuclear cells from vaccinees, but not placebo recipients, secreted interleukin 2 (IL-2), IL-5, and gamma interferon (IFN-␥) in response to in vitro stimulation with HPV-11 VLP. The proliferation-based SI was moderately correlated with IFN-␥ production and significantly correlated with IL-2 production after the third immunization (P ‫؍‬ 0.078 and 0.002, respectively). The robust lymphoproliferative responses were specific for HPV-11, since SIs generated against bovine papillomavirus and HPV-16 VLPs were not generally observed and when detected were similar pre-and postimmunization.Human papillomaviruses (HPVs) are small double-stranded DNA viruses that infect cutaneous and mucosal epithelial cells and cause benign and malignant hyperproliferative lesions, such as genital warts and cervical cancer (56). Condylomata acuminatum (genital warts) is the most commonly diagnosed sexually transmitted viral disease in the United States (29), and approximately 95% of genital warts are caused by infection with the low-risk HPV types 6 and 11 (HPV-6 and -11) (5, 16). Although genital warts do not have a propensity for malignant transformation, they are a cause of great psychosocial morbidity. Since all available therapies are associated with high rates of recurrence, the development of a vaccine to prevent the occurrence of HPV-6 and -11-induced lesions is needed. The present study was designed to evaluate the immunogenicity of a virus-like particle (VLP)-based HPV-11 vaccine in a phase I human trial.While early clinical studies of HPV VLP-based vaccines are presently under way, little is understood about the immune responses generated in vaccine recipients and the specific types of cellular immunity that will be required for long-term prot...

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L1-Specific Protection from Tumor Challenge Elicited by HPV16 Virus-like Particles

Cited by 62 publications

References 19 publications

How will HPV vaccines affect cervical cancer?

How will HPV vaccines affect cervical cancer?

B Lymphocyte Activation by Human Papillomavirus-Like Particles Directly Induces Ig Class Switch Recombination via TLR4-MyD88

Priming of Human Papillomavirus Type 11-Specific Humoral and Cellular Immune Responses in College-Aged Women with a Virus-Like Particle Vaccine

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