Incorporation of RG1 epitope into HPV16L1-VLP does not compromise L1-specific immunity.

The candidate pan-Human Papillomavirus (HPV) vaccine RG1-VLP are HPV16 major capsid protein L1 virus-like-particles (VLP) comprising a type-common epitope of HPV16 minor capsid protein L2 (RG1; aa17-36). Vaccinations have previously demonstrated efficacy against genital high-risk (hr), low-risk (lr) and cutaneous HPV. To compare RG1-VLP to licensed vaccines, rabbits (n = 3) were immunized thrice with 1 µg, 5 µg, 25 µg, or 125 µg of RG1-VLP or a 1/4 dose of Cervarix®. 5 µg of RG1-VLP or 16L1-VLP (Cervarix) induced comparable HPV16 capsid-reactive and neutralizing antibodies titers (62,500/12,500-62,500 or 1000/10,000). 25 µg RG1-VLP induced robust cross-neutralization titers (50-1000) against hrHPV18/31/33/45/52/58/26/70. To mimic reduced immunization schedules in adolescents, mice (n = 10) were immunized twice with RG1-VLP (5 µg) plus 18L1-VLP (5 µg). HPV16 neutralization (titers of 10,000) similar to Cervarix and Gardasil and cross-protection against hrHPV58 vaginal challenge was observed. RG1-VLP vaccination induces hrHPV16 neutralization comparable to similar doses of licensed vaccines, plus cross-neutralization to heterologous hrHPV even when combined with HPV18L1-VLP.

Safety and immunogenicity of BPV-1 L1 virus-like particles in a dose-escalation vaccination trial in horses.

REASONS FOR PERFORMING STUDY: Infection with bovine papillomaviruses types 1 and 2 (BPV-1, BPV-2) can lead to the development of therapy-resistant skin tumours termed sarcoids and possibly other skin diseases in equids. Although sarcoids seriously compromise the welfare of affected animals and cause considerable economic losses, no prophylactic vaccine is available to prevent this common disease. In several animal species and man, immunisation with papillomavirus-like particles (VLP) has been shown to protect efficiently from papillomaviral infection. HYPOTHESIS: BPV-1 L1 VLPs may constitute a safe and highly immunogenic vaccine candidate for protection of horses against BPV-1/-2-induced disease. METHODS: Three groups of 4 horses each received 50, 100 or 150 µg of BPV-1 L1 VLPs, respectively, on Days 0, 28 and 168. Three control horses received adjuvant only. Horses were monitored on a daily basis for one week after each immunisation and then in 2 week intervals. Sera were collected immediately before, 2 weeks after each vaccination and one and 2 years after the final boost and analysed by pseudovirion neutralisation assay. RESULTS: None of the horses showed adverse reactions upon vaccination apart from mild and transient swelling in 2 individuals. Irrespective of the VLP dose, all VLP-immunised horses had developed a BPV-1-neutralising antibody titre of ≥ 1600 plaque forming units (pfu)/ml 2 weeks after the third vaccination. Eight of 10 trial horses still available for follow-up had neutralising antibody titres ≥ 1600 pfu/ml one year and ≥ 800 pfu/ml 2 years after the last immunisation. CONCLUSION: Intramuscular BPV-1 L1 VLP vaccination in horses is safe and results in a long-lasting antibody response against BPV-1. Neutralisation titres were induced at levels that correlate with protection in experimental animals and man. POTENTIAL RELEVANCE: BPV-1 L1 VLPs constitute a promising vaccine candidate for prevention of BPV-1/-2-induced disease in equids.

[HPV infections of the oral and genital mucosa. Possibilities for primary prevention]. / HPV-Infektionen der Mund- und Genitalschleimhaut. Möglichkeiten der primären Prävention.

It is well accepted today that almost all cases of carcinoma of the cervix are caused by persistent infections with high-risk human papilloma viruses (HPV), especially through types HPV16 and HPV18 (ca. 70%). These same types are also responsible for some carcinomas of the vulva, anus, penis and oropharynx. This knowledge indicates that it should be possible to prevent these carcinomas if a majority of the causstive HPV infections can be prevented.

A subset of equine sarcoids harbours BPV-1 DNA in a complex with L1 major capsid protein.

Bovine papillomavirus type 1 or 2 (BPV-1, BPV-2) are accepted causal factors in equine sarcoid pathogenesis. Whereas viral genomes are consistently found and expressed within lesions, intact virions have never been detected, thus permissiveness of sarcoids for BPV-1 replication remains unclear. To reassess this issue, an immunocapture PCR (IC/PCR) was established using L1-specific antibodies to capture L1-DNA complexes followed by amplification of the viral genome. Following validation of the assay, 13 sarcoid-bearing horses were evaluated by IC/PCR. Samples were derived from 21 tumours, 4 perilesional/intact skin biopsies, and 1 serum. Tissue extracts from sarcoid-free equines served as controls. IC/PCR scored positive in 14/24 (58.3%) specimens obtained from sarcoid-patients, but negative for controls. Quantitative IC/PCR demonstrated <125 immunoprecipitable viral genomes/50 microl extract for the majority of specimens. Moreover, full-length BPV-1 genomes were detected in a complex with L1 proteins. These complexes may correspond to virion precursors or intact virions.