Biology
William Bonnez in Guide to Genital HPV Diseases and Prevention, 2019
Due to strict species- and tissue-specificities of these viruses and their requirement for differentiating epithelium for completion of the viral life cycle, growth of HPV genotypes in the laboratory for a long time was impossible, and remains difficult and complex. This is why for research purposes, one still relies on animal papillomavirus models such as the cottontail rabbit papillomavirus, the bovine papillomavirus, and the canine oral papillomavirus. HPV-1, then HPV-11, and later HPV-16 were first grown, beginning in 1985, by infecting small fragments of human epithelial tissue (mostly neonatal foreskin), and implanting them under the renal capsule of immunodeficient mice (athymic “nude” mice or animals with the severe combined immunodeficiency syndrome). In this type of model the viral infection recapitulates the macroscopic, microscopic, and molecular features of a natural infection. It has been possible since, to grow HPV in skin organotypic (artificial skin) culture systems.
Cidofovir and Brincidofovir
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
The preliminary results obtained in the cottontail rabbit papillomavirus model indicated that CDV could offer some therapeutic solutions for the treatment of lesions caused by HPV. Indeed, complete and permanent remissions of papilloma lesions have been achieved after topical gel applications as well as direct intralesional or intravenous injections of CDV (Christensen et al., 2000; Duan et al., 2000). In rabbits infected with cottontail rabbit papillomavirus, Duan et al. demonstrated that topical CDV was very effective at inhibiting papillomavirus-induced wart growth if it was initiated early in infection, especially with low titers of inoculum (Duan et al., 2000).
Landscape of Papillomavirus in Human Cancers
Satya Prakash Gupta in Cancer-Causing Viruses and Their Inhibitors, 2014
Preclinical studies have demonstrated that bovine or rabbit immunizations with L2 polypeptides protect against papillomavirus type 4 at mucosal sites in the bovine and at cutaneous sites in the cottontail rabbit papillomavirus (Lin et al. 1992; Campo et al. 1993; Embers et al. 2002). This suggests that immunization against the minor capsid protein 2 might work as a pan-HPV vaccine against various genotypes of papillomaviruses. Inoculation of amino-terminal L2 polypeptides also induced protection against heterologous papillomavirus types. Vaccination with HPV-16 L2 (amino acids 11–200) protects against cottontail rabbit papillomavirus (CRPV) and rabbit oral papillomavirus, both evolutionarily divergent from HPV-16 (Gambhira et al. 2007). Vaccination with BPV-1 L2 (amino acids 1–88) peptides produces sera with cross-neutralizing activity against different HPVs. Human volunteers vaccinated with the candidate prophylactic/therapeutic vaccine HPV-16 L2E6E7 fusion protein induced L2-specific antibodies that also neutralized a divergent type of HPV (Gambhira et al. 2006; WHO 2006). The monovalent L2 immunogens generate neutralizing titers that are greater for the homologous type of virus than for a heterologous type papillomavirus. The lower immune response to heterologous HPVs could severely limit the breadth and duration of protection of an L2-based vaccine. To address this issue and provide broader immunity, the L2-neutralizing epitope was inserted on the surfaces of VLPs increasing the titers of neutralizing antibodies nearly tenfold (Slupetzky et al. 2007). A synthetic L2 lipopeptide in which the cross neutralizing L2 peptide is linked to both a T-helper epitope and a ligand for TLR2. Tandem repetition of the same peptide displayed on bacterial thioredoxin, multitype L2 fusion proteins from different papillomavirus types have been utilized in inducing cross-neutralizing antibodies against several clinically relevant HPV types (Alphs et al. 2008; Jagu et al. 2009).
The current status of gene therapy in bladder cancer
Published in Expert Review of Anticancer Therapy, 2023
Côme Tholomier, Alberto Martini, Sharada Mokkapati, Colin P. Dinney
Significant scientific advances identified special properties of viruses that allowed them to deliver genes into the cells of interest. This led to a shift from bacterial to viral gene therapy. This led to a shift of focus to the development of viral rather than bacterial gene therapy. Using the Rous sarcoma RNA virus, Temin et al. infected chicken cells which then expressed specific viral gene mutations [10]. Similarly, using the Tobacco mosaic virus, a polyadenylate stretch of genetic material was introduced into viral RNA [11]. This was followed by the first human gene therapy trial in which the Shope papilloma virus was employed to introduce an arginase gene in two patients with a urea cycle disorder using [12,13]. Despite the negative results, research in gene therapy continued and the first trial with a therapeutic attempt in human was approved by the FDA in 1990 [14]. This was then followed by other gene therapy trials across the world. The tragic death of a patient secondary to an overwhelming inflammatory response following the systemic administration of an adenovirus was a sobering wakeup call that underlined the knowledge gaps that needed to be overcome to safely deliver viral therapy to patients [15].
Pharmacotherapy for recurrent respiratory papillomatosis (RRP): a treatment update
Published in Expert Opinion on Pharmacotherapy, 2021
One approach to tackle RRP would be to inactivate HPV with a therapeutic vaccine. Such a vaccine would be required to induce a T cell response and kill HPV infected cells. The HPV DNA encodes for late proteins which make the protective shell of the virion and early proteins which are necessary for viral function. Arguably the most important of the early proteins are E6 and E7, which target p53 and Rb (retinoblastoma) tumor suppressor proteins [70]. The cottontail rabbit papillomavirus (CRPV) is established as a laboratory test model for RRP. E6 and E7 peptide-specific antibodies have been identified in rabbit serum post vaccination with overlapping E6 and E7 peptides, resulting in a reduction of latent CRPV DNA hence control of CRPV-induced papilloma [71].
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