Quadrivalent vaccine against human papillomaviruses (HPV)

Abstract

Humani papilomavirusi (HPV) su iznimno heterogena grupa DNA virusa koja ima vrlo važnu ulogu u etiologiji različitih benignih i malignih novotvorina pločastog epitela. Prevencija HPV infekcije postiže se primjenom rekombinantnog cjepiva koje sadrži virusima-slične čestice (viral-like particles, VLP) te u cijepljenih osoba potiče sintezu neutralizirajućih protutijela specifičnih za pojedine virusne genotipove. VLPsu prazne, neinfektivne virusne kapside koje ne sadrže DNA i koje su morfološki identične nativnim virusima što ih čini odličnim kandidatima za proizvodnju profilaktičkih cjepiva. Klinička ispitivanja faze I i II dokazala su dobru podnošljivost VLP-cjepiva protiv HPV-a, njihovu sposobnost indukcije visokog titra neutralizirajućih protutijela (50–100 puta veši titar u usporedbi s prirodnom infekcijom) kao i vrlo veliku učinkovitost u zaštiti od uspostave perzistentne HPV infekcije te posljedične pojave bolesti. Kliničko ispitivanje faze III završeno je za samo jedno cjepivo protiv HPV-a tj. za četverovalentno cjepivo koje sadrži VLP genotipova HPV-6, HPV-11, HPV-16 i HPV-18 proizvođača tvrtke Merck Sharpe & Dohme (Gardasil®, Silgard®). Do siječnja 2007. g. četverovalentno cjepivo protiv HPV-a odobreno je u 52 zemlje (po žurnom postupku) uključujući SAD, 25 članica Europske Unije, Meksiko, Australiju, Novi Zeland, Peru i Brazil. Cjepivo je trenutno u postupku registracije u još približno pedesetak država. Literaturni podatci pokazuju da su tijekom dosadašnje primjene cjepiva najčešće zabilježene vrlo blage nuspojave, uglavnom lokalne reakcije na mjestu cijepljenja.Human papillomaviruses (HPV) are remarkably heterogeneous group of DNA viruses that are causally involved in the etiology of different benign and malignant neoplastic lesions of the anogenital, oropharyngeal and cutaneous epithelium. The prevention of HPV infection can be achieved by the induction of genotype-specific neutralizing antibodies triggered by recombinant L1 viral-like particle (VLP) vaccines. VLP are attractive candidates for prophylactic vaccines as they are empty, non-infectious, DNA-free viral capsids morphologically indistinguishable from the native viruses. Phase I and II trials have shown that the VLP-based HPV vaccines are well tolerated, that they induce high titers of neutralizing antibodies (50–100 fold greater than during natural infection), and protect with a very high efficacy against a persistent HPV infection and HPV-related clinical disease. Until now only one HPV vaccine completed phase III trials. The vaccine produced by Merck Sharpe & Dohme (Gardasil®, Silgard®), is a quadrivalent vaccine with HPV-6, HPV-11, HPV-16, and HPV-18 VLPs. Until January 2007, the quadrivalent HPV vaccine has been approved in 52 countries (all under accelerated review schedules) including the US, all 25 European Union member countries, Mexico, Australia, Canada, New Zealand, Peru and Brasil. Additional applications are currently under review with regulatory agencies in more than 50 countries around the world. According to the published data, the vaccine has been associated with minimal adverse reactions, the most common of which being local reactions