Minor Capsid Protein of Human Genital Papillomaviruses Contains Subdominant, Cross-Neutralizing Epitopes

Roden, Richard B.S.; Yutzy, William H.; Fallon, Rosemary; Inglis, Stephen; Lowy, Douglas R.; Schiller, John T.

doi:10.1006/viro.2000.0272

Cited by 219 publications

(205 citation statements)

References 21 publications

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“…As trials of HPV vaccines are designed, it is critical that assays are developed that can conclusively demonstrate infection (or absence of infection) with the specific HPV types included in the vaccine. This is especially important because many HPV types can cause cervical dysplasia, and there appears to be little or no ''cross-protection'' of HPV vaccines currently under development [Roden et al, 2000]. In addition, it is essential to discriminate between true infection of cervical tissue, and HPV that has been deposited near the cervix as a result of sexual activity.…”

Section: Discussionmentioning

confidence: 99%

Detection of specific human papillomavirus types in paraffin‐embedded sections of cervical carcinomas

Bryan

Taddeo

Skulsky

et al. 2005

Journal of Medical Virology

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Human papillomaviruses (HPV) are the causative agents of most cervical carcinomas. A complete understanding of the HPV types that cause cervical carcinoma is needed as vaccines are designed. Fresh tissues are not always available for such studies. We therefore sought to determine the feasibility of HPV studies using formalinfixed, paraffin-embedded sections of 56 cervical carcinomas, correlating typing information with the pathology and physical state of the HPV sequences within cells. Sections from each specimen were used to extract and purify DNA. Specific HPV types were identified using a PCR/ reverse blot strip assay. Tyramide signal-amplified, fluorescent DNA in situ hybridization (FISH) was used to localize HPV within cells. Human b-globin sequences were amplified in DNA from all specimens. HPV sequences from oncogenic types were identified in 52 of 56 (92.9%) by PCR/ reverse blot strip assay, and in one additional case using an HPV 16 multiplex PCR assay. HPV 16 was the most commonly detected type, present in most cases as a solitary isolate. Thirtyfive of 42 HPV 16 or HPV 18 PCR-positive specimens were also positive in the FISH assay, in most cases in a pattern consistent with viral integration. We conclude that HPV typing from formalin-fixed, paraffin-embedded sections of cervical carcinomas is possible, with a sensitivity that is similar to that found in studies using fresh tissue.

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Section: Discussionmentioning

confidence: 99%

Detection of specific human papillomavirus types in paraffin‐embedded sections of cervical carcinomas

Bryan

Taddeo

Skulsky

et al. 2005

Journal of Medical Virology

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“…Cross-reactive neutralising epitopes have, however, been found on L2 when expressed as a separate polypeptide: the L2 of HPV-16 contains cross-neutralising epitopes to HPV types 6, 16, and 18 (75). The aa sequence region 108-120 of the HPV 16 L2 contains a common-neutralising epitope for HPV types 6 and 16 (76).…”

Section: Chimaeric Vlp Vaccinesmentioning

confidence: 99%

Human Papillomavirus (HPV) Infection in Southern Africa: Prevalence, Immunity, and Vaccine Prospects

et al. 2002

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SummaryHuman papillomavirus (HPV) associated cancers are more prevalent in developing countries compared to developed countries. The major cancer caused by HPV is cervical cancer. The humoral immune response to HPV can be a marker of past infection but may also reflect persistent infection and cervical disease. IgA antibodies to HPV in oral fluid were also found to be markers of cervical disease. Cell mediated immunity is important in clearing HPV infection and for regression of the associated lesions: this means that women infected with HIV have a high prevalence of co-infection with HPV. Good cervical screening programmes can control HPV associated cervical neoplasia. However, in countries such as South Africa, where these programmes are inadequate, there is a need for an HPV vaccine. The development of HPV vaccines is reviewed. There is a call for an inexpensive vaccine that will be accessible to the women that do not have access to adequate screening programmes and are therefore at the greatest risk of cervical cancer. IUBMB Life, 53: 253-258, 2002

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“…Immunization with minor capsid protein L2 peptides in animal models protects them from experimental papillomavirus infection at both mucosal and cutaneous sites (10,11). Protection is mediated by neutralizing antibodies, and the work of several laboratories has identified cross-neutralizing epitopes (10)(11)(12)(13)(14)(15)(16)(17)(18).…”

mentioning

confidence: 99%

“…Protection is mediated by neutralizing antibodies, and the work of several laboratories has identified cross-neutralizing epitopes (10)(11)(12)(13)(14)(15)(16)(17)(18). We have previously reported that monoclonal antibody RG-1, which is specific for residues 17-36 of L2 from HPV16, neutral-izes both HPV16 and HPV18 and protects naïve mice from challenge with HPV16 (12).…”

mentioning

confidence: 99%

Protection against heterologous human papillomavirus challenge by a synthetic lipopeptide vaccine containing a broadly cross-neutralizing epitope of L2

Alphs¹,

Gambhira²,

Karanam³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Persistent infection with the high-risk subset of genitotropic human papillomavirus (HPV) genotypes is a necessary cause of cervical cancer. Given the global burden of cervical cancer, a low-cost, broadly protective vaccine is needed. RG-1 is a crossneutralizing and protective monoclonal antibody that recognizes residues 17-36 of HPV16 minor capsid protein L2. Because this epitope is highly conserved in divergent HPV types, we determined whether vaccination with HPV16 L2 17-36 peptide is broadly protective. The peptide was administered to BALB/c mice three times at monthly intervals, either alone or in the context of a synthetic lipopeptide vaccine candidate (P25-P2C-HPV) produced by linkage of the HPV peptide with a broadly recognized T helper epitope (P25) and the Toll-like receptor-2 (TLR2) ligand dipalmitoyl-S-glyceryl cysteine (P2C). In contrast to vaccination with the L2 17-36 peptide or P25-P2C alone, a potent L2-specific antibody response was generated to the P25-P2C-HPV lipopeptide when delivered either s.c. or intranasally. Sera from mice vaccinated with the P25-P2C-HPV lipopeptide neutralized not only HPV16 pseudovirions but also other evolutionarily divergent oncogenic genital (HPV18, HPV45) and cutaneous (HPV5, BPV1) types. The L2-specific antibody response depended on MHC class II, CD40, and MyD88 signaling. Additionally, vaccination with the P25-P2C-HPV lipopeptide protected mice from homologous challenge with HPV16 pseudovirions at cutaneous and genital sites and heterologous challenge with HPV45 pseudovirions. If provided in the appropriate context, therefore, HPV16 L2 17-36 might be used in a totally synthetic cross-protective HPV vaccine. G enitotropic human papillomavirus (HPV) infections are considered the most common sexually transmitted infection in the United States (1). The major manifestations of anogenital HPV include genital warts (condyloma acuminatum) and anogenital intraepithelial neoplasia. If left untreated, a small fraction of persistent high-risk HPV infections progresses to cancer. The presence of HPV DNA has been reported in 99.7% of cervical carcinomas worldwide, indicating that HPV infection is a necessary cause of this cancer and that this disease can be prevented by prophylactic HPV vaccination (2).Approximately 35 of the Ͼ100 subtypes of HPV are specific for the anogenital epithelium and have varying potentials for malignant transformation (3). Of the 15 oncogenic genital HPV types, HPV16 is the most common, followed by HPV18 and HPV45 (contributing Ϸ50%, 20%, and 10%, respectively, of cervical cancer cases worldwide). Public health efforts have successfully reduced the incidence and mortality of cervical cancer with the implementation of cervical cytology screening programs. Women who do not undergo regular screening account for most of the patients with invasive cancers (4), and cervical cancer remains the second most common cause of cancer death in women worldwide and the most prevalent cancer in women of sub-Saharan Africa, Central America, south-central Asia, and Me...

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Minor Capsid Protein of Human Genital Papillomaviruses Contains Subdominant, Cross-Neutralizing Epitopes

Cited by 219 publications

References 21 publications

Detection of specific human papillomavirus types in paraffin‐embedded sections of cervical carcinomas

Detection of specific human papillomavirus types in paraffin‐embedded sections of cervical carcinomas

Human Papillomavirus (HPV) Infection in Southern Africa: Prevalence, Immunity, and Vaccine Prospects

Protection against heterologous human papillomavirus challenge by a synthetic lipopeptide vaccine containing a broadly cross-neutralizing epitope of L2

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