Human Papillomavirus Vaccine

5 Jun

Because certain subtypes of human papillomavirus (HPV) are associated with the  development of cervical cancer, the  search for  a  prophylactic or  therapeutic HPV  vaccine has  been  an important endeavor. Although more  than 30 types of HPV are known to be sexually transmittable, the  major types associ- ated with malignancy (HPV-16, -18, -31, -33, -45, -52, and  -58) and  condylomata (HPV-6  and  -11) are  relatively few in num- ber, allowing for  more  focused strategies  for  immunization against these specific  subtypes. Vaccine development has  been hampered in the  past because of the  inability to culture HPV. However, an in vitro  culture system for HPV has  more  recently been  developed, furthering the  prospect for advancements in this field  (269).  Virus-like particle (VLP)  vaccines are  pro- duced by recombinant DNA  technology and  are  designed to self-assemble into  conformations that resemble natural  HPV. These vaccines contain no  viral DNA  and  carry no  risk of infection or  oncogenic exposure. VLP  vaccines have been designed for all of the  major HPV  subtypes and  clinical trials are  currently underway for HPV-11 L1 VLP (270), HPV-6  L1 VLP (271), and  HPV-16 L1 VLP (272).

Fusion protein vaccines are currently under evaluation for the  immunotherapy of cervical cancer and  genital warts. TA- HPV is a live recombinant vaccinia virus which has  been  engi- neered to express the  E6 and  E7 protein genes for HPV-16 and -18 as a treatment for cervical cancer (212).  This  method also utilizes the  viral vector  approach, using vaccinia as  a vehicle. Viral  vector  vaccines can  be polyvalent and  have the  potential to produce immunity similar to that induced by live attenuated vaccines. A phase I/II clinical trial of TA-HPV  (273) has  shown encouraging results, and  further studies are  underway. TA-GW is a recombinant fusion protein vaccine consisting of HPV-6  L2 and  E7 proteins, which is under investigation for the treatment of genital warts. A phase IIa clinical trial showed the  vaccine to be immunogenic, with encouraging clinical responses (274). A third protein vaccine, TA-CIN, is in preclinical development for the  treatment of cervical dysplasia (212).

Peptide-based vaccines have been  shown to be protective against HPV-induced tumors in mice, although the  T-cell rep- ertoires in  mice  and  humans differ. Two  early-stage human clinical trials are  underway, one involving HLA A*0201 bind- ing  HPV-16 E7  peptides, to  assess the  possible therapeutic implications these vaccines may  offer (275). Other investiga- tional approaches to  HPV  immunization include DNA  vac- cines  (275), bacterial  vectors (276–278), and  dendritic cells pulsed with HPV  epitopes (279). Koutsky reported in a study of 2392  young  women that a HPV-16 VLP vaccine was  100% effective in preventing HPV-16 infection. In addition, the  vac- cine was  safe,  with no serious side  effects  reported. Therefore, immunization of HPV-16–negative women may  eventually reduce the  incidence of cervical cancer (280).

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