Characterization of Immunoglobulin A/G Responses During 3 Doses of the Human Papillomavirus-16/18 ASO4-Adjuvanted Vaccine.

BACKGROUND: Individuals receiving the human papillomavirus (HPV) vaccine develop high levels of circulating neutralizing antibodies. However, data about antibody responses in the cervix are limited. METHODS: This study was designed to describe the course of IgA/IgG responses in cervical secretions and in serum after intramuscular administration of the HPV16/18 AS04-adjuvant vaccine. An enzyme-linked immunosorbent assay for detection of IgA and IgG anti-HPV-VLP was developed for this purpose. RESULTS: Immunoglobulin G seroconversion after the second dose was observed in 100% of the participants and remained 1 month after the third dose. Regarding IgG reactivity in cervical secretions, conversion was observed in 85% of women after the final dose. Immunoglobulin A seroconversion was observed in 76.7% of women after the third dose. Lower levels of IgA were detected in the cervical mucus (28.3%) and decreased to 23.3% after the last dose. Comparing local and systemic IgG responses, positivity in both serum and cervical samples was observed in 85%, whereas in 15% only, the serum was IgG antibody positive. A weak agreement between local and systemic IgA responses was observed. Only 18.3% of participants were local and systemic IgA positive, 58.4% were positive only in serum, 5% were positive only in the cervix, and 18.3% were both local and systemic IgA antibody negative. CONCLUSIONS: After the third vaccination, there is a strong agreement between cervical and systemic IgG antibody responses and a weak agreement between cervical and systemic IgA antibody responses. The induction of IgA antibodies seems to be secondary to that of IgG antibodies in response to HPV intramuscular vaccination.

Detection of immunoglobulin IgA and IgG against human papilloma virus.

The interest in human papilloma virus (HPV) seropositivity has increased considerably since HPV vaccines have become available worldwide. The aim of this study was to assess the performance of enzyme-linked immunosorbent assay (ELISA) in analyzing serum samples provided from women with and without genital DNA-HPV infection confirmed by polymerase chain reaction (PCR), for detection of specific antibodies of the isotypes IgG and IgA recognizing HPV-16 and -18, as well as virus-like particles (VLPs). From August to December 2013, 50 sexually active female patients between 18 and 35 years of age from the outpatient clinic at the university hospital were enrolled. In order to test them, positive controls were obtained from patients with HPV-induced lesions and who were DNA-HPV positive confirmed by PCR. A specific assay was used to identify antibodies to HPV VLPs by ELISA. The samples were divided into HPV positive and negative, and an ELISA detecting IgA and IgG anti-HPV-VLP was carried out. The effectiveness of ELISA and the kappa (k) index was obtained from the values entered in the receiver operating characteristic (ROC) curves for IgG and IgA. IgG-VLP-HPV-16 showed a good correlation between ELISA and PCR (k=0.75), and IgG-VLP-HPV-18 showed a very good correlation between ELISA and PCR (k=0.84). While the IgA antibody correlation was also positive, although weaker, IgA-VLP-HPV-16 was moderate (k=0.45) and IgA-VLP-HPV-18 good (k=0.66). The efficacy of the assay concerning IgG was: sensitivity, specificity, and accuracy were 82.3%, 92%, and 88% to IgG-VLP-HPV-16, and 100%, 92%, and 94% to IgG-VLP-HPV-18. The assay concerning IgA was: sensitivity, specificity, and accuracy were 64.7%, 80%, and 73.8% to IgA-VLP-HPV-16, and 100%, 80%, and 84.8% to IgA-VLP-HPV-18. IgG and IgA antibodies against HPV-16 and -18 can be detected in unvaccinated individuals by using the VLP that serve as the basis for bivalent HPV vaccine. The values for ELISA assays and the values found for IgG correlate good/very good with HPV-16/18 detected by PCR.