Developments in L2-based human papillomavirus (HPV) vaccines

Schellenbacher, Christina; Roden, Richard B.S.; Kirnbauer, Reinhard

doi:10.1016/j.virusres.2016.11.020

Cited by 64 publications

(52 citation statements)

References 92 publications

(96 reference statements)

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“…In order to extend the type-restricted protection provided by current L1-VLP HPV vaccines towards more distantly related types, several groups have employed the minor capsid protein L2 of PV as immunogen, which can induce low-level neutralizing antibodies to the homologous types, and also cross-neutralization to heterologous HPV types [25]. Several type-common epitopes have been identified within the highly conserved N-terminal amino acids (aa) 11–200 of L2.…”

Section: Introductionmentioning

confidence: 99%

Chimeric L2-Based Virus-Like Particle (VLP) Vaccines Targeting Cutaneous Human Papillomaviruses (HPV)

et al. 2017

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Common cutaneous human papillomavirus (HPV) types induce skin warts, whereas species beta HPV are implicated, together with UV-radiation, in the development of non-melanoma skin cancer (NMSC) in immunosuppressed patients. Licensed HPV vaccines contain virus-like particles (VLP) self-assembled from L1 major capsid proteins that provide type-restricted protection against mucosal HPV infections causing cervical and other ano-genital and oro-pharyngeal carcinomas and warts (condylomas), but do not target heterologous HPV. Experimental papillomavirus vaccines have been designed based on L2 minor capsid proteins that contain type-common neutralization epitopes, to broaden protection to heterologous mucosal and cutaneous HPV types. Repetitive display of the HPV16 L2 cross-neutralization epitope RG1 (amino acids (aa) 17–36) on the surface of HPV16 L1 VLP has greatly enhanced immunogenicity of the L2 peptide. To more directly target cutaneous HPV, L1 fusion proteins were designed that incorporate the RG1 homolog of beta HPV17, the beta HPV5 L2 peptide aa53-72, or the common cutaneous HPV4 RG1 homolog, inserted into DE surface loops of HPV1, 5, 16 or 18 L1 VLP scaffolds. Baculovirus expressed chimeric proteins self-assembled into VLP and VLP-raised NZW rabbit immune sera were evaluated by ELISA and L1- and L2-based pseudovirion (PsV) neutralizing assays, including 12 novel beta PsV types. Chimeric VLP displaying the HPV17 RG1 epitope, but not the HPV5L2 aa53-72 epitope, induced cross-neutralizing humoral immune responses to beta HPV. In vivo cross-protection was evaluated by passive serum transfer in a murine PsV challenge model. Immune sera to HPV16L1-17RG1 VLP (cross-) protected against beta HPV5/20/24/38/96/16 (but not type 76), while antisera to HPV5L1-17RG1 VLP cross-protected against HPV20/24/96 only, and sera to HPV1L1-4RG1 VLP cross-protected against HPV4 challenge. In conclusion, RG1-based VLP are promising next generation vaccine candidates to target cutaneous HPV infections.

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Section: Introductionmentioning

confidence: 99%

Chimeric L2-Based Virus-Like Particle (VLP) Vaccines Targeting Cutaneous Human Papillomaviruses (HPV)

et al. 2017

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“…Considering the need for a broader coverage of the HPV vaccine, some researchers have been focused on developing a new generation HPV vaccine with a focus on the minor capsid protein, L2. [106][107][108][109] Highly conserved peptides of the L2 protein was shown to induce cross-neutralizing and cross-protective antibody responses against multiple high-risk HPV types. [110][111][112] It is promising that the HPV vaccine based on the L2 protein could be an effective new generation vaccine.…”

Section: Cost-effectiveness Of the 9vhpv Vaccinationmentioning

confidence: 99%

Expanded strain coverage for a highly successful public health tool: Prophylactic 9-valent human papillomavirus vaccine

Zhang

Xia

et al. 2017

Human Vaccines & Immunotherapeutics

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Human papillomavirus is considered the causative factor for cervical cancer, which accounts for approximately 5% of the global cancer burden and more than 600,000 new cases annually that are attributable to HPV infection worldwide. The first-generation prophylactic HPV vaccines, Gardasil® and Cervarix®, were licensed approximately a decade ago. Both vaccines contain the most prevalent high-risk types, HPV16 and 18, which are associated with 70% of cervical cancer. To further increase the type coverage, 5 additional oncogenic HPV types (31, 33, 45, 52 and 58) were added to the existing Gardasil-4 to develop a 9-valent HPV vaccine (9vHPV), Gardasil 9®, increasing the potential level of protection from ∼70% to ∼90%. The efficacy of the vaccine lies primarily in its ability to elicit type-specific and neutralizing antibodies to fend off the viral infection. Therefore, type-specific and neutralizing murine monoclonal antibodies (mAbs) were used to quantitate the antigenicity of the individual vaccine antigens and to measure the antibody levels in the serum samples from vaccinees in a type- and epitope-specific manner in a competitive immunoassay. Assays for 9vHPV are extended from the proven platform used for 4vHPV by developing and adding new mAbs against the additional types. In Phase III clinical trials, comparable safety profile and immunogenicity against the original 4 types were demonstrated for the 9vHPV vaccine, and these were comparable to the 4vHPV vaccine. The efficacy of the 9vHPV vaccine was established in trials with young women. Immunobridging for younger boys and girls was performed, and the results showed higher immunogenicity in the younger age group. In a subsequent clinical trial, the 2-dose regimen of the 9vHPV vaccine used among girls and boys aged 9-14 y showed non-inferior immunogenicity to the regular 3-dose regimen for young women (aged 16-26 years). Overall, the clinical data and cost-effectiveness analysis for the 9vHPV vaccine support its widespread use to maximize the impact of this important, life-saving vaccine.

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“…Unfortunately, the L2 protein is not very immunogenic, and several approaches are being used trying to increase its immunogenicity. These include producing a recombinant protein in bacteria, an expression system in Lactobacillus casei for possible oral immunization, and production of L2 VLP derived from bacteriophage PP7 [82,85].…”

Section: New Prophylactic Vaccinesmentioning

confidence: 99%

Prophylactic and Therapeutic Vaccines against Human Papillomavirus Infections

Rosales¹,

Rosales²

2017

Vaccines

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Human papillomaviruses (HPVs) are a large family of double-strand DNA viruses comprising more than 180 types. Infection with HPV is associated with benign and malignant proliferation of skin and mucosae. Low-risk HPVs produce warts, whereas high-risk viruses induce tumors. Because there are no anti-viral drugs for HPV infection, there is a lot of interest in vaccines that can prevent the infection and also in vaccines that can be used to treat established infections and HPV-related tumors. Two prophylactic vaccines have been approved for preventing HPV infection. They seem to be efective when very young people are vaccinated. Unfortunately, many older people are still at risk of infection, mainly in countries where vaccination coverage is not eicient and for those people, novel therapeutic vaccines are being developed. This chapter describes the properties of HPV vaccines used today and the current status of several therapeutic vaccines been developed to treat HPV-induced lesions.

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Developments in L2-based human papillomavirus (HPV) vaccines

Cited by 64 publications

References 92 publications

Chimeric L2-Based Virus-Like Particle (VLP) Vaccines Targeting Cutaneous Human Papillomaviruses (HPV)

Chimeric L2-Based Virus-Like Particle (VLP) Vaccines Targeting Cutaneous Human Papillomaviruses (HPV)

Expanded strain coverage for a highly successful public health tool: Prophylactic 9-valent human papillomavirus vaccine

Prophylactic and Therapeutic Vaccines against Human Papillomavirus Infections

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