Comparison of the immunogenicity of Cervarix<sup>®</sup>and Gardasil<sup>®</sup>human papillomavirus vaccines for oncogenic non-vaccine serotypes HPV-31, HPV-33, and HPV-45 in HIV-infected adults

Toft, Lars; Tolstrup, Martin; Müller, Martin; Sehr, Peter; Bonde, Jesper; Storgaard, Merete; Østergaard, Lars; Søgaard, Ole Schmeltz

doi:10.4161/hv.27925

Cited by 48 publications

(53 citation statements)

References 38 publications

(48 reference statements)

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“…the titres of 17-year-olds vaccinated at the age of 12 years are higher than those 17-year-olds vaccinated at the age of 15 years) [45][46][47][48]. (4) 2vHPV, due presumably to its adjuvant, induces greater antibody titres vs. HPV16 and HPV18 and invokes higher titres of cross-protective antibodies against untargeted HPV genotypes than 4vHPV [50][51][52][53][54]. (4) 2vHPV, due presumably to its adjuvant, induces greater antibody titres vs. HPV16 and HPV18 and invokes higher titres of cross-protective antibodies against untargeted HPV genotypes than 4vHPV [50][51][52][53][54].…”

Section: Humoral Immune Responsesmentioning

confidence: 99%

Prophylactic HPV vaccination: past, present, and future

Castle

Maza²

2015

Epidemiol. Infect.

143

114

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Human papillomavirus (HPV) is the necessary cause of cervical cancer, the fourth most common cancer and cause of cancer-related death in females worldwide. HPV also causes anal, vaginal, vulvar, penile, and oropharyngeal cancer. Prophylactic HPV vaccines based on recombinantly expressed virus-like particles have been developed. Two first-generation, U.S. Food and Drug Administration (FDA)-approved vaccines prevent infections and disease caused by HPV16 and HPV18, the two HPV genotypes that cause approximately 70% of cervical cancer, and one of these vaccines also prevents HPV6 and HPV11, the two HPV genotypes that cause 90% of genital warts. A next-generation vaccine, recently approved by the U.S. FDA, targets HPV16, HPV18, and five additional HPV genotypes that together causes approximately 90% of cervical cancer as well as HPV6 and HPV11. In clinical trials, these vaccines have shown high levels of efficacy against disease and infections caused by the targeted HPV genotypes in adolescent females and males and older females. Data indicate population effectiveness, and therefore cost effectiveness, is highest in HPV-naive young females prior to becoming sexually active. Countries that implemented HPV vaccination before 2010 have already experienced decreases in population prevalence of targeted HPV genotypes and related anogenital diseases in women and via herd protection in heterosexual men. Importantly, after more than 100 million doses given worldwide, HPV vaccination has demonstrated an excellent safety profile. With demonstrated efficacy, cost-effectiveness, and safety, universal HPV vaccination of all young, adolescent women, and with available resources at least high-risk groups of men, should be a global health priority. Failure to do so will result in millions of women dying from avertable cervical cancers, especially in low- and middle-income countries, and many thousands of women and men dying from other HPV-related cancers.

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Section: Humoral Immune Responsesmentioning

confidence: 99%

Prophylactic HPV vaccination: past, present, and future

Castle

Maza²

2015

Epidemiol. Infect.

143

114

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“…HPV vaccinations have proven safe and immunogenic in immunosuppressed patients, inducing seroconversion in 95–100% of HIV-positive patients, but antibody titers were lower compared to healthy controls, which might be improved by additional vaccine boosts [21–23]. Importantly, a prevalent infection with one vaccine-targeted HPV type did not negatively influence antibody induction against other vaccine types, and no effect was seen on CD4+ cell counts or HIV RNA levels.…”

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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“…In the 12-month follow-up period it was observed that HIV-infected women but not men reacted more strongly against Cervarix compared with Gardasil. Both vaccines induced comparable titers of neutralizing antibodies against nonvaccine HPV-31, -33 and -45 [60]. It would be interesting to determine long-term persistence of antibody titers in these study populations.…”

Section: Hpv Vaccination Of Hiv-positive and Immunosuppressed Individualsmentioning

confidence: 96%

Current Perspectives on HPV Vaccination: A Focus on Targeting the L2 Protein

Seitz

Müller

2014

Future Virol.

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Thirty years ago, human papillomavirus types 16 and 18 were isolated from cervical carcinomas, and it has been almost 10 years since the introduction of the first prophylactic virus-like particle (VLP) vaccine. The VLP vaccines have already impacted the reduction of pre-malignant lesions and genital warts, and it is expected that vaccination efforts will successfully lower the incidence of cervical cancer before the end of the decade. Here we summarize the historical developments leading to the prophylactic HPV vaccines and discuss current advances of next-generation vaccines that aim to overcome certain limitations of the VLP vaccines, including their intrinsic narrow range of protection, stability and production/distribution costs. KEYWORDS• cervical cancer • emerging HPV-associated diseases • human papillomavirus • major capsid protein L1-based virus-like particle vaccines • markers for protection • minor capsid protein L2-based crossprotective vaccines • neutralizing antibodies • nonavalent VLP vaccine • second-generation HPV vaccine • vaccine accessibility and production/ distribution costs Introduction & historyOver the last 150 years the recognition of papillomaviruses as causative agents for a number of malignancies in both animals and humans has evolved. In the 1960s sufficient evidence began accumulating demonstrating a causative role of certain human papillomaviruses (HPVs) in the development of cervical cancer beyond reasonable doubt [1]. Numerous investigations, among them a large number of epidemiological studies, were required to reach this point. As of 2007 we stand with two successful commercial prophylactic vaccines that efficiently protect against the most prevalent oncogenic HPV types.Early observations reported by the Italian physician Rigoni-Stern already hinted at the involvement of infectious agents in the development of cervical cancer when he suggested behavioral risks for this type of tumor [2]. These investigations were eventually resumed in the second half of the 20th century. Not only was the risk for cervical cancer attributed to genital infection, those studies eventually acquitted some of the suspects; for example, an involvement of herpes simplex virus 2 could be ruled out [3].In the 1970s HPV-6 and HPV-11 were isolated and cloned from condylomas and laryngeal papillomas, respectively. At this time, Harald zur Hausen had noted that condylomas and cervical carcinomas share a similar epidemiological pattern and this initiated the systematic hunt for novel papillomaviruses. The strategy at the time utilized Southern blot hybridization techniques under low stringency conditions using the DNA of already isolated HPV types as molecular probes. Within a few years a large number of human and animal papillomavirus genomes had been isolated [4][5][6][7]. Of the more than 200 papillomaviruses known today, many are infecting the genital epithelium and approximately 13 of them are recognized as human oncogenic viruses [8].In the following years it became evident that most if not all cases of ...

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Comparison of the immunogenicity of Cervarix^®and Gardasil^®human papillomavirus vaccines for oncogenic non-vaccine serotypes HPV-31, HPV-33, and HPV-45 in HIV-infected adults

Cited by 48 publications

References 38 publications

Prophylactic HPV vaccination: past, present, and future

Prophylactic HPV vaccination: past, present, and future

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

Current Perspectives on HPV Vaccination: A Focus on Targeting the L2 Protein

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Comparison of the immunogenicity of Cervarix®and Gardasil®human papillomavirus vaccines for oncogenic non-vaccine serotypes HPV-31, HPV-33, and HPV-45 in HIV-infected adults

Cited by 48 publications

References 38 publications

Prophylactic HPV vaccination: past, present, and future

Prophylactic HPV vaccination: past, present, and future

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

Current Perspectives on HPV Vaccination: A Focus on Targeting the L2 Protein

Contact Info

Product

Resources

About

Comparison of the immunogenicity of Cervarix^®and Gardasil^®human papillomavirus vaccines for oncogenic non-vaccine serotypes HPV-31, HPV-33, and HPV-45 in HIV-infected adults