Abstract
BackgroundHuman papillomaviruses (HPV) are the most common sexually transmitted viruses. Infection of the cervical epithelium by HPVs can lead to the development of cervical cancer. Recent advances in vaccine research have shown that immunization with papillomavirus-like particles (VLPs) containing the major structural viral protein, L1 from HPV 16 can provide protection from the establishment of a chronic HPV 16 infection and related cervical intraepithelial neoplasia (CIN) in baseline HPV 16 naïve women.MethodsTo better understand the quantitative and qualitative effects of aluminum adjuvant on the immunogenic properties of an HPV 6, 11, 16 and 18L1 VLP vaccine, we used an HPV-specific, antibody isotyping assay and a competitive immunoassay that measures antibodies to neutralizing epitopes to profile sera from rhesus macaques immunized with the HPV L1 VLP vaccine formulated with or without aluminum adjuvant.ResultsImmunization with VLPs formulated with the aluminum adjuvant elicited a significantly stronger immune response with higher peak antibody titers both at four weeks post vaccination (12.7 to 41.9-fold higher) as well as in the persistent phase at week 52 (4.3 to 26.7-fold higher) than that of VLPs alone. Furthermore, the aluminum adjuvant formulated HPV VLP vaccine elicited a predominantly T helper type 2 response, with high levels of IgG1 and IgG4 and low levels of IgG2. The vaccine also elicited high levels of serum IgA, which may be important in providing mucosal immunity to impart protection in the anogenital tract.ConclusionThese results show that the HPV 6, 11, 16 and 18 L1-VLP vaccine formulated with Merck aluminum adjuvant elicits a robust and durable immune response and holds promise as a vaccine for preventing cervical cancer.
Highlights
Human papillomaviruses (HPV) are the most common sexually transmitted viruses
Peak antibody titers four weeks post dose 3, at week 28, for all four HPV types were 12.7 to 41.9-fold higher for the group vaccinated with virus-like particles (VLP) + Merck Aluminum Adjuvant (MAA) compared to the group vaccinated with VLPs alone, and between 4.3 to 26.7-fold higher in the persistence phase at week 52 (Table 2A)
Results from the HPV competitive Luminex Immunoassay (cLIA) showed that the vaccine induced antibodies that competed with monoclonal antibodies (MAbs) to known neutralizing epitopes, and are, theoretically able to neutralize HPV
Summary
Infection of the cervical epithelium by HPVs can lead to the development of cervical cancer. HPV infection is the obligate first step in the development of cervical cancer [1]. A large portion of this health burden is in the developing world, where women do not have access to good healthcare and Papanicolaou (Pap) screens. The widespread use of Pap screening in the developed world has increased the early detection of cervical dysplasia and cancer, thereby improving treatment outcomes for cervical cancer, it would be far more preferable to have a vaccine that blocks HPV infection, thereby preventing initiation of the disease process. Developing countries that usually do not have access to Pap screening and other preventive measures would further benefit from a vaccine that blocks HPV infection and its subsequent disease consequences. There is a great need for an effective and generally well-tolerated HPV vaccine, having a low rate of occurrence of adverse events during administration
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
