Reactivity of human sera in a sensitive, high-throughput pseudovirus-based papillomavirus neutralization assay for HPV16 and HPV18

Pastrana, Diana V.; Buck, Christopher B.; Pang, Yuk Ying S.; Thompson, Cynthia D.; Castle, Philip E.; Fitzgerald, Peter; Kjær, Susanne K.; Lowy, Douglas R.; Schiller, John T.

doi:10.1016/j.virol.2003.12.027

Cited by 337 publications

(351 citation statements)

References 54 publications

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“…18 A cross-neutralizing monoclonal anti-L2 antibody, K4L2 [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] , highly potent at neutralizing HPV 16 and other high-risk HPV pseudovirions (PSV), fails to neutralize HPV 31. Vice versa, an anti-HPV 31 L2 neutralizing antibody (K3L2 [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] ) is not able to neutralize HPV 16 PSV. Also, anti-HPV 16 L2 polyclonal sera neutralize HPV 31 pseudovirions with a low efficiency (Seitz et al, unpublished data).…”

Section: Resultsmentioning

confidence: 99%

“…This fact could raise some doubts about the true existence of the HPV 31 D31N variant, which might require independent confirmation, despite the fact that PSV carrying this exchange proved to be highly infectious in vitro. HPV 31 type-specific K3L2 [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] neutralized HPV 31 reference and P34T pseudovirions as well as D31N pseudovirions albeit the latter to a lower degree. Likewise, the polyclonal sera from HPV 31 antigenimmunized mice neutralized HPV 31 reference and P34T pseudovirions equally well, while D31N was neutralized to a lesser extent.…”

Section: Discussionmentioning

confidence: 99%

“…The HPV 18 L2h template plasmid was obtained from J. Schiller's lab 25 and the HPV 31 L2h and HPV 51 L2h plasmids from T. Kanda's lab. 14,26 Pseudovirion preparation…”

Section: Site-directed Mutagenesismentioning

confidence: 99%

“…Two monoclonal antibodies, K18L2 [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] and K3L2 [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] , as well as five polyclonal sera were tested on the HPV 31 reference and variant pseudovirions in a neutralization assay. Although K18L2 [20][21][22][23][24][25][26][27][28][29][30][31][32]…”

Section: Neutralization Of Hpv 31 D31n and P34t L2 Variantsmentioning

confidence: 99%

“…Neutralization of HPV 18 P33H, P33N and P29S 1 P33N L2 variants HPV 18 L2 reference, P33H, P33N and P29S þ P33N pseudovirions were tested in an in vitro neutralization assay with cross-neutralizing antibodies K4L2 [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] and K18L2 20-38 and 10 polyclonal sera.…”

Section: Neutralization Of Hpv 31 D31n and P34t L2 Variantsmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…The HPV 18 L2h template plasmid was obtained from J. Schiller's lab 25 and the HPV 31 L2h and HPV 51 L2h plasmids from T. Kanda's lab. 14,26 Pseudovirion preparation…”

Section: Site-directed Mutagenesismentioning

confidence: 99%

Section: Neutralization Of Hpv 31 D31n and P34t L2 Variantsmentioning

confidence: 99%

Section: Neutralization Of Hpv 31 D31n and P34t L2 Variantsmentioning

confidence: 99%

See 3 more Smart Citations

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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HPVVaccine

Inglis

2009

Encyclopedia of Life Sciences

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HPVVaccines

Wilkinson

Inglis

2015

Encyclopedia of Life Sciences

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The discovery in the early 1970s that cervical cancer was caused by infection with human papillomavirus ( HPV ) stimulated a highly successful vaccine development programme based on the use of recombinant deoxyribonucleic acid ( DNA ) technology to produce virus proteins in a form that can stimulate powerful and long‐lasting antibody responses. The vaccines have been designed as combinations to target the HPV virus types that are responsible for most human disease. Clinical trials have shown that it is possible to prevent both genital warts and the early stages of cervical cancer through vaccination and this has led to licensure and use of HPV vaccines in many countries throughout the world. Progression from initial virus infection to development of invasive cancer is often very slow, however, and so it will be many years before the impact of the vaccine on the overall disease burden is fully understood. Key Concepts Vaccine development for HPV has been complex but highly successful. Successful vaccines were made by recombinant protein expression to produce virus‐like particles (VLPs). Prevention of papillomavirus‐induced disease requires neutralising antibodies at the mucosal site of infection. The main public health priority was to achieve high coverage in vaccinating women with the aim to prevent cervical cancer. Prophylactic HPV vaccine efficacy has been remarkably high. Some cross‐protection is observed between different vaccine types. HPV vaccines have been implemented in populations of young women widely around the world. Access to affordable HPV vaccines in poor countries is a key goal but remains a challenge. The scope of HPV vaccination extends to the prevention of non‐cervical HPV infections and related diseases in both females and males.

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Reactivity of human sera in a sensitive, high-throughput pseudovirus-based papillomavirus neutralization assay for HPV16 and HPV18

Cited by 337 publications

References 54 publications

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

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

HPVVaccine

HPVVaccines

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