RG2-VLP: a Vaccine Designed to Broadly Protect against Anogenital and Skin Human Papillomaviruses Causing Human Cancer

Olczak, Pola; Matsui, Ken; Wong, Margaret; Alvarez, Jade; Lambert, Paul F.; Christensen, Neil D.; Hu, Jiafen; Huber, Birgit; Kirnbauer, Reinhard; Wang, Joshua W; Roden, Richard B.S.

doi:10.1128/jvi.00566-22

Cited by 12 publications

(6 citation statements)

References 88 publications

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“…Prophylactic HPV vaccination is a remarkably effective preventive measure for HPV-associated diseases, but current vaccines immunize against only the most common ( 2–9 ) HPV types ( 34 ). Our data provide a rationale for including additional HPV types in the development of new vaccines and highlight the potential of pan-HPV vaccines ( 35, 36 ).…”

Section: Discussionmentioning

confidence: 84%

Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell–like Program Conserved in HPV-Positive Cancers

et al. 2022

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The skin is exposed to viral pathogens, but whether they contribute to the oncogenesis of skin cancers has not been systematically explored. Here we investigated 19 skin tumor types by analyzing off-target reads from commonly available next-generation sequencing data for viral pathogens. We identified human papillomavirus 42 (HPV42) in 96% (n = 45/47) of digital papillary adenocarcinoma (DPA), an aggressive cancer occurring on the fingers and toes. We show that HPV42, so-far considered a non-oncogenic, “low-risk” HPV, recapitulates the molecular hallmarks of oncogenic, “high-risk” HPVs. Using machine learning, we find that HPV-driven transformation elicits a germ cell-like transcriptional program conserved throughout all HPV-driven cancers (DPA, cervical carcinoma, and head and neck cancer). We further show that this germ cell-like transcriptional program, even when reduced to the top 2 genes (CDKN2A, SYCP2), serves as a fingerprint of oncogenic HPVs with implications for early detection, diagnosis, and therapy of all HPV-driven cancers.

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Section: Discussionmentioning

confidence: 84%

Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell–like Program Conserved in HPV-Positive Cancers

et al. 2022

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“…However, after HPV16 RG1 vaccination, five out of six animals cross-reacted against MnPV L2 and only three were cross-neutralizing in FC-PBNAs (Figure 2). Such an observation was recently reported for the nonavalent Gardasil ® 9 vaccine which could also not confer complete protection against some targeted HPV typesamongst them HPV16 -in a heterologous cutaneous rabbit challenge model (44). Therefore, it is not only necessary to find robust in vitro criteria but also adequate natural PV-infection models that allow a conclusive and reliable prediction of the in vivo protection efficacy of different HPV vaccines (45)(46)(47).…”

Section: Discussionmentioning

confidence: 89%

“…However, it is reasonable to assume that the HPV16 RG1-VLP vaccine in the form used here is limited in its efficacy to induce a broad cross-protection against cutaneous HPVs. The problem of low RG1 epitope sequence identity between mucosal and cutaneous HPV was already recognized and recently experimentally addressed by Olczak et al ( 44 ), who combined the consensus RG1 epitope of betapapillomaviruses and the mucosal HPV16 RG1 in DE loops of VLPs, which revealed a higher potential to broadly cross-neutralize skin-specific PV types. Although optimizations are still needed, L2-based vaccination strategies have great, though not unlimited, potential to induce broad-based cross-protective immunity against cutaneous HPVs and related diseases.…”

Section: Discussionmentioning

confidence: 99%

Next generation L2-based HPV vaccines cross-protect against cutaneous papillomavirus infection and tumor development

et al. 2022

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Licensed L1-VLP-based immunizations against high-risk mucosal human papillomavirus (HPV) types have been a great success in reducing anogenital cancers, although they are limited in their cross-protection against HPV types not covered by the vaccine. Further, their utility in protection against cutaneous HPV types, of which some contribute to non-melanoma skin cancer (NMSC) development, is rather low. Next generation vaccines achieve broadly cross-protective immunity against highly conserved sequences of L2. In this exploratory study, we tested two novel HPV vaccine candidates, HPV16 RG1-VLP and CUT-PANHPVAX, in the preclinical natural infection model Mastomys coucha. After immunization with either vaccines, a mock control or MnPV L1-VLPs, the animals were experimentally infected and monitored. Besides vaccine-specific seroconversion against HPV L2 peptides, the animals also developed cross-reactive antibodies against the cutaneous Mastomys natalensis papillomavirus (MnPV) L2, which were cross-neutralizing MnPV pseudovirions in vitro. Further, both L2-based vaccines also conferred in vivo protection as the viral loads in plucked hair after experimental infection were lower compared to mock-vaccinated control animals. Importantly, the formation of neutralizing antibodies, whether directed against L1-VLPs or L2, was able to prevent skin tumor formation and even microscopical signs of MnPV infection in the skin. For the first time, our study shows the proof-of-principle of next generation L2-based vaccines even across different PV genera in an infection animal model with its genuine PV. It provides fundamental insights into the humoral immunity elicited by L2-based vaccines against PV-induced skin tumors, with important implications to the design of next generation HPV vaccines.

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“…The vaccine achieves this by integrating 20 amino acid-conserved protective epitopes derived from the minor capsid protein into the HPV16 and HPV18 L1 virus-like particles (VLP). This strategic incorporation enhances its potential utility and effectiveness in addressing a broad spectrum of HPV infections, particularly those associated with the diverse βHPV subgroup [ 116 ].…”

Section: Discussionmentioning

confidence: 99%

Unveiling the Therapeutic Horizon: HPV Vaccines and Their Impact on Cutaneous Diseases—A Comprehensive Review

Șandru,

Radu,

Petca

et al. 2024

Vaccines

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Human papillomavirus (HPV) encompasses a diverse array of viruses, comprising approximately 200 serotypes that affect humans. While the majority of HPV strains are associated with benign skin or mucous membrane growths, a subset is implicated in severe health conditions, such as cervical, anal, vulvar, and vaginal cancers. Despite the established effectiveness of HPV vaccines in preventing cervical and anal carcinomas in particular, their therapeutic potential in addressing cutaneous diseases linked to diverse HPV strains remains an intriguing area of investigation. This narrative review critically examines the existing literature to assess the viability of HPV immunization as a therapeutic intervention for prevalent cutaneous conditions. These include genital and extragenital cutaneous warts, epidermodysplasia verruciformis, and keratinocyte carcinomas. The findings suggest a promising dual role for HPV vaccines in preventing and treating dermatologic conditions while emphasizing future research directions, including the immunization perspective against β-HPVs. Moreover, the presence of conflicting study outcomes underscores the imperative for larger-scale, randomized trials with well-matched control groups to validate the efficacy of HPV immunization in the dermatologic context. This review contributes valuable insights into the evolving landscape of HPV-vaccine applications in the field of dermatology.

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RG2-VLP: a Vaccine Designed to Broadly Protect against Anogenital and Skin Human Papillomaviruses Causing Human Cancer

Cited by 12 publications

References 88 publications

Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell–like Program Conserved in HPV-Positive Cancers

Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell–like Program Conserved in HPV-Positive Cancers

Next generation L2-based HPV vaccines cross-protect against cutaneous papillomavirus infection and tumor development

Unveiling the Therapeutic Horizon: HPV Vaccines and Their Impact on Cutaneous Diseases—A Comprehensive Review

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