Monoclonal Antibodies to HPV-6 L1 Virus-like Particles Identify Conformational and Linear Neutralizing Epitopes on HPV-11 in Addition to Type-Specific Epitopes on HPV-6

Christensen, Neil D.; Reed, Cynthia A.; Cladel, Nancy M.; Hall, Kathleen; Leiserowitz, Gary S.

doi:10.1006/viro.1996.0554

Cited by 109 publications

(93 citation statements)

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“…Vaccination with L1 VLPs elicits a polyclonal response that includes neutralizing antibodies directed against numerous epitopes displayed on the VLP surface. 15,29,40,41 Various assays are available to measure antibodies elicited by HPV L1 VLP vaccines. Some immunoassays are designed to measure a broad Titers are recorded in arbitrary units specific for the assay (i.e., IgG GMT mMU/mL and cLIa GMT mMU/mL).…”

Section: Discussionmentioning

confidence: 99%

“…It is known that immunization with HPV or VLPs elicits a broad, polyclonal response that recognizes many epitopes found on the capsid surface. 15,29,40,41 In natural infection, however, it is not known if a single neutralizing antibody provides complete protection, or if in fact, many antibodies may be required, working singly or in combination, to achieve complete protection. For HPV 16, the most thoroughly studied HPV type with regard to antibodymediated neutralization, an immunodominant epitope (V5) within L1 has been described, which elicits antibody responses in most naturally infected women.…”

Section: Methodsmentioning

confidence: 99%

“…35,36 On each VLP there are neutralizing epitopes that may or may not be HPV type-specific, as well as epitopes that are non-neutralizing. 15,29,40,41,[52][53][54][55][56] The cLIA is a multiplex assay that involves the displacement of a phycoerythrin (PE)-labeled HPV type-specific, VLP-conformation dependent, neutralizing monoclonal antibody (mAb): H6.M48, K11.B2, H16.V5 and H18.J4 for the HPV 6, 11, 16 and 18 assays, respectively. 35,36 Luminex microspheres are coated with HPV type 6, 11, 16 and 18 L1 VLPs and incubated with the PE-labeled mAbs.…”

Section: Total Igg Luminex Immunoassay (Totalmentioning

confidence: 99%

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The humoral response to Gardasil over four years as defined by Total IgG and competitive Luminex immunoassay

et al. 2011

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Total Igg Luminex Immunoassay (Totalmentioning

confidence: 99%

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The humoral response to Gardasil over four years as defined by Total IgG and competitive Luminex immunoassay

et al. 2011

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“…The HPV-9 cLIA uses the same 4 mAbs as that used in the HPV-4 cLIA for HPV types 6, 11, 16 and 18: H6.M48, K11.B2, H16.V5, and H18.J4. 3,8,9 As few mAbs exist for the rarer oncogenic types, Merck generated panels of mAbs to the HPV L1 VLPs of HPV types 31, 33, 45, 52, and 58. The generation and characterization of the panels of mAbs to these HPV types, as well as the selection of the pairs of antibodies that were of high affinity, type-specific, and recognized conformationdependent neutralizing epitopes, has been previously described.…”

mentioning

confidence: 99%

Development of a human papillomavirus competitive luminex immunoassay for 9 HPV types

Roberts

Green²,

Hess

et al. 2014

Human Vaccines & Immunotherapeutics

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“…The latter is due to the fact that neutralizing anti-L1 binds to surface loops on the viral capsids, which are highly heterogeneous among the different HPV types. [10][11][12] In fact, every HPV genotype analyzed to date represents a separate serotype, and, that is why, with very few exceptions, anti-L1 neutralizing antibodies are highly HPV-type specific. Combined with the observation that L1 is the most conserved papillomavirus protein, one can conclude that the escape of naturally existing neutralizing antibodies has been a major driving factor in the evolution of papillomaviruses.…”

mentioning

confidence: 99%

Natural variants in the major neutralizing epitope of human papillomavirus minor capsid protein L2

Seitz

Schmitt

Böhmer³

et al. 2012

Intl Journal of Cancer

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The amino terminus of the human papillomavirus minor capsid protein L2 contains a major cross-neutralizing epitope that provides the basis for the development of a broadly protective HPV vaccine. This attainable broad protection would eliminate one of the major drawbacks of the commercial L1-based prophylactic vaccines. In this study, we asked whether there are natural variants of the L2 cross-neutralizing epitope and if these variants provide means for immune escape from vaccineinduced anti-L2 antibodies. For this, we isolated in silico and in vitro, a total of 477 L2 sequences of HPV types 16, 18, 31, 45, 51, 52 and 58. We identified natural L2 epitope variants for HPV 18, 31, 45 and 51. To determine whether these variants escape L2-directed neutralization, we generated pseudovirions encompassing the natural variants and tested these in an in vitro neutralization assay using monoclonal and polyclonal antibodies. Our results indicate that natural variants of the L2 major neutralizing epitope are frequent among two different study populations from Germany and Mongolia and in the GenBank database. Of two identified HPV 31 L2 single amino acid variants, one could be neutralized well, while the other variant was neutralized very poorly. We also observed that single amino acid variants of HPV 18 and 45 are neutralized well while a HPV 18 double variant was neutralized at significantly lower rates, indicating that L2 variants have to be accounted for when developing HPV L2-based prophylactic vaccines.Human papillomaviruses (HPVs) are the causative agents for the development of cervical cancer. Close to 100% of tumors from the uterine cervix harbor sequences of HPVs; at least 15 different types are linked to cancer, and these are termed as ''oncogenic HPV types.'' 1 Worldwide, the 10 most frequently isolated HPV types in cervical cancer are HPV 16,18,33, 45,31, 58, 52,35, 59 and 56. 2 In general, however, infection with genital HPV is common in adults, and most infections are cleared by the immune system. The most frequent HPV types isolated in women with normal cytology are, in order of prevalence, HPV 16, 42, 58,31,18, 56, 81,35,33, 45 and 52. 3 Although other factors contribute to the malignant transformation process, it is generally accepted that HPV infection is an absolute requirement. 4,5 Built on the recognition of HPV infection in the etiology of cervical cancer, two commercial vaccines, Gardasil V R and Cervarix V R , have been licensed in 2006 and 2007, respectively. 6,7 Both vaccines are based on the L1 major capsid protein and are highly effective in preventing HPV infection and HPV-induced cervical lesions. 8,9 It is expected that both vaccines will reduce the cervical cancer rate in vaccinated women by 70-80%.Both L1-based vaccines have some limitations including costly production, invasive administration and limited protection against nonvaccine HPV types. The latter is due to the fact that neutralizing anti-L1 binds to surface loops on the viral capsids, which are highly heterogeneous among the dif...

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Monoclonal Antibodies to HPV-6 L1 Virus-like Particles Identify Conformational and Linear Neutralizing Epitopes on HPV-11 in Addition to Type-Specific Epitopes on HPV-6

Cited by 109 publications

References 0 publications

The humoral response to Gardasil over four years as defined by Total IgG and competitive Luminex immunoassay

The humoral response to Gardasil over four years as defined by Total IgG and competitive Luminex immunoassay

Development of a human papillomavirus competitive luminex immunoassay for 9 HPV types

Natural variants in the major neutralizing epitope of human papillomavirus minor capsid protein L2

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