Characterization of a human papillomavirus type 16 variant-dependent neutralizing epitope

Roden, Richard B.S.; Armstrong, A.; Haderer, P.; Christensen, Neil D.; Hubbert, Nancy L.; Lowy, Douglas R.; Schiller, John T.; Kirnbauer, Reinhard

doi:10.1128/jvi.71.8.6247-6252.1997

Cited by 112 publications

(68 citation statements)

References 36 publications

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“…Similarly, we examined whether peptide insertion in the FG hypervariable region of HPV-16 L1 would disrupt HPV-16 cross-reacting MAb-binding to VLPs by ELISA. Since five HPV-31 MAbs cross-react with HPV-16, we investigated their reactivity with wild-type HPV-16 L1 VLPs and two mutants previously created by insertion of a short heterologous sequence within the FG loop of HPV-16 L1 protein at positions 266/267 and 283/284 [30]. In contrast to the binding observed with the H16.V5 MAb, the binding of which is affected by insertion at both positions [30], MAb binding to VLPs was affected by insertion at position 266/267, but not by insertion at position 283/284 for H31.B5, H31.E22, H31.C9, and H31.F7.…”

Section: Discussionmentioning

confidence: 99%

“…These MAbs will be important tools in attempts to monitor immunity developed in HPV vaccine recipients and to further characterize the protective epitopes on HPV-31 virions. HPV-31 mutants are therefore currently under development in order to investigate whether type-specific neutralizing MAbs are directed against the FG loop or not, as observed with HPV-16 [14,30,32].…”

Section: Discussionmentioning

confidence: 99%

“…Anti-HPV monoclonal antibodies have been generated against the L1 protein of different human papillomavirus types, and they have been used to map the neutralization epitopes for types 6,11,16, and 31 [4,[24][25][26]43].All conformationdependent monoclonal antibody epitopes identified to date are type-specific and have been found to reside on the VLP surface within hypervariable loops, with the exception of the H16.U4 MAb, which was recently demonstrated to bind the C-terminal arm of HPV-16 L1 between residues 427 and 445 [4]. L1 binding sites of neutralizing monoclonal antibodies raised against L1 VLPs include residues within the DE loop for type 11 [24,25], residues within BC and EF loops for type 6 [27], and residues within the FG loop for type 16 [30,32,43]. Only one MAb (H31.A6) has been produced for HPV-31 [9].…”

Section: Introductionmentioning

confidence: 99%

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Identification of type-specific and cross-reactive neutralizing conformational epitopes on the major capsid protein of human papillomavirus type 31

et al. 2006

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The majority of the neutralizing epitopes of papillomaviruses (PV) are conformation-specific and have not been fully characterised. Studies have, to date, been limited to a few HPV types only. We analysed the epitopes on the major capsid protein (L1) of Human papillomavirus (HPV) type 31 using monoclonal antibodies (MAbs) generated against HPV-31 virus-like particles (VLPs). The type-specific MAbs against HPV-31 were all found to be neutralizing and recognized conformation-dependent epitopes. Two other MAbs directed against a conformational epitope were found to be cross-reactive with other HPV types, and one of them was found to be cross-neutralizing. Cross-reactive antibodies were further investigated using wild-type HPV-16 L1 VLPs and two mutants. The results obtained suggested the existence of a cross-neutralizing conformational epitope at the N-terminal part of the FG loop of the major capsid protein, and the other four cross-reactive MAbs recognized epitopes also located at the N-terminal part of the FG loop.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of type-specific and cross-reactive neutralizing conformational epitopes on the major capsid protein of human papillomavirus type 31

et al. 2006

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“…This system served as an in vitro model to identify the BPV-1 cellular receptor [30]. In a separate study, Semliki Forest virus was chosen by Roden et al to express the papillomavirus virion proteins for generating infectious pseudotyped papillomaviruses in vitro [31]. This system has not only permitted the analysis of the ability of antibody cross-type neutralization but also provided insight into the mechanism and specificity of papillomavirus genome packaging and infection.…”

Section: Mimicking Native Virions With Hpv Pseudovirionsmentioning

confidence: 99%

Functional assessment and structural basis of antibody binding to human papillomavirus capsid

Zhang

Modis

et al. 2015

Reviews in Medical Virology

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Persistent high-risk human papillomavirus (HPV) infection is linked to cervical cancer. Two prophylactic virus-like particle (VLP)-based vaccines have been marketed globally for nearly a decade. Here, we review the HPV pseudovirion (PsV)-based assays for the functional assessment of the HPV neutralizing antibodies and the structural basis for these clinically relevant epitopes. The PsV-based neutralization assay was developed to evaluate the efficacy of neutralization antibodies in sera elicited by vaccination or natural infection or to assess the functional characteristics of monoclonal antibodies. Different antibody binding modes were observed when an antibody was complexed with virions, PsVs or VLPs. The neutralizing epitopes are localized on surface loops of the L1 capsid protein, at various locations on the capsomere. Different neutralization antibodies exert their neutralizing function via different mechanisms. Some antibodies neutralize the virions by inducing conformational changes in the viral capsid, which can result in concealing the binding site for a cellular receptor like 1A1D-2 against dengue virus, or inducing premature genome release like E18 against enterovirus 71. Higher-resolution details on the epitope composition of HPV neutralizing antibodies would shed light on the structural basis of the highly efficacious vaccines and aid the design of next generation vaccines. In-depth understanding of epitope composition would ensure the development of function-indicating assays for the comparability exercise to support process improvement or process scale up. Elucidation of the structural elements of the type-specific epitopes would enable rational design of cross-type neutralization via epitope re-engineering or epitope grafting in hybrid VLPs.

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“…61,96 The HPV16 L1-specific neutralizing Mabs, H16.V5 and H16.E70, prevent endocytosis of virions but not the ability of the virions to bind to the surface of HaCaT cells. 74,97 Interestingly, they do block binding of HPV16 particles to erythrocytes and to extracellular matrix, 33,97,98 suggesting two distinct modes of binding to cell surfaces. These two antibodies also prevent a conformational change in the virion that allows the cleavage of approximately 13 amino acids from the amino terminus of L2 by furin.…”

Section: Mechanisms Of Viral Neutralizationmentioning

confidence: 99%

Developing vaccines against minor capsid antigen L2 to prevent papillomavirus infection

et al. 2009

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A subset of human papillomavirus (HPV) genotypes is responsible for ~5% of all cancer deaths globally, and uterine cervical carcinoma accounts for the majority of these cases. Their impact is greatest for women who do not have access to effective secondary preventive measures, and consequently over 80% of cervical cancer deaths worldwide occur in Developing nations. The understanding that persistent infection by this ‘oncogenic’ subset of HPV genotypes is necessary for the development of cervical carcinoma has driven the development of preventive vaccines. Two preventive vaccines comprising recombinant HPV L1 virus-like particles (VLPs) have been licensed. However, the current cost of these vaccines precludes global delivery, and they target only two of the ~15 known oncogenic HPV types, although ~70% of cervical cancer cases are attributed to these two types and there is evidence for some degree of cross-protection against other closely related types. A possible approach to broader immunity at lower cost is to consider vaccination against L2. L2 vaccines can be produced inexpensively and they also have the promise of conferring much broader cross-type protective immunity than observed with L1 VLP immunization. However, L2 vaccine development lags behind L1 VLP vaccines and several technical hurdles remain.

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Characterization of a human papillomavirus type 16 variant-dependent neutralizing epitope

Cited by 112 publications

References 36 publications

Identification of type-specific and cross-reactive neutralizing conformational epitopes on the major capsid protein of human papillomavirus type 31

Identification of type-specific and cross-reactive neutralizing conformational epitopes on the major capsid protein of human papillomavirus type 31

Functional assessment and structural basis of antibody binding to human papillomavirus capsid

Developing vaccines against minor capsid antigen L2 to prevent papillomavirus infection

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