Correlation between levels of human papillomavirus (HPV)-16 and 18 antibodies in serum and cervicovaginal secretions in girls and women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine
Central Laboratory and Vaccination Centre, Stiftung Juliusspital, Wuerzburg, Germany. Human vaccines
(Impact Factor: 3.64).
12/2010; 6(12):1054-61. DOI: 10.4161/hv.6.12.13399
This pooled analysis of data from four Phase III clinical trials was undertaken to assess the correlation between levels of anti-human papillomavirus (HPV)-16/18 antibodies in serum and cervicovaginal secretions (CVS) in girls and women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine. Serum and CVS samples were collected from a subset of women aged 10-65 years (N=350) at pre-specified time-points from 7 to 36 months post-vaccination. Anti-HPV-16/18 antibody levels in serum and CVS were measured by enzyme-linked immunosorbent assay. Pearson correlation coefficients between serum and CVS antibody levels, standardized for total immunoglobulin G, were calculated at each time-point in women with detectable antibodies in both serum and CVS. All subjects had seroconverted at Month 7 and remained seropositive through Month 36 for both antigens. Geometric mean titers of anti-HPV-16/18 antibodies in serum were substantially higher at all time-points than those in a control group of women who had cleared a natural HPV infection in another trial. In women with detectable antibodies in both serum and CVS, good correlation was seen between HPV-16/18 antibody levels at all time-points (Pearson correlation coefficient: 0.84-0.92 for HPV-16 and 0.90-0.91 for HPV-18). The strong correlation between levels of HPV-16/18 antibodies in serum and CVS up to 36 months post-vaccination in girls and women vaccinated with the HPV-16/18 AS04-adjuvanted vaccine supports transudation of serum antibodies as the mechanism by which antibodies are introduced into CVS. These CVS antibodies may play a role in the protective efficacy of this vaccine.
Available from: plosone.org
- "For vaccinees with detectable antibodies in both serum and genital secretions, the HPV-specific antibody titer was normalized to the total IgG level in the serum or genital sample, respectively, and reported as the HPV specific IgG/total IgG serum. Following a test for normality (Shapiro-Wilk test), supported by a normal quantile (Q-Q) plot, Pearson's correlation (r) was used to evaluate the relationship between the Log10 normalized values for these two sample types . "
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ABSTRACT: The current generation of Human Papillomavirus (HPV) vaccines, Cervarix® and Gardasil®, exhibit a high degree of efficacy in clinical trials against the two high-risk (HR) genotypes represented in the vaccines (HPV16 and HPV18). High levels of neutralizing antibodies are elicited against the vaccine types, consistent with preclinical data showing that neutralizing antibodies can mediate type-specific protection in the absence of other immune effectors. The vaccines also confer protection against some closely related non-vaccine HR HPV types, although the vaccines appear to differ in their degree of cross-protection. The mechanism of vaccine-induced cross-protection is unknown. This study sought to compare the breadth and magnitudes of neutralizing antibodies against non-vaccine types elicited by both vaccines and establish whether such antibodies could be detected in the genital secretions of vaccinated individuals.
Serum and genital samples were collected from 12-15 year old girls following vaccination with either Cervarix® (n = 96) or Gardasil® (n = 102) HPV vaccine. Serum-neutralizing antibody responses against non-vaccine HPV types were broader and of higher magnitude in the Cervarix®, compared to the Gardasil®, vaccinated individuals. Levels of neutralizing and binding antibodies in genital secretions were closely associated with those found in the serum (r = 0.869), with Cervarix® having a median 2.5 (inter-quartile range, 1.7-3.5) fold higher geometric mean HPV-specific IgG ratio in serum and genital samples than Gardasil® (p = 0.0047). There was a strong positive association between cross-neutralizing antibody seropositivity and available HPV vaccine trial efficacy data against non-vaccine types.
These data demonstrate for the first time that cross-neutralizing antibodies can be detected at the genital site of infection and support the possibility that cross-neutralizing antibodies play a role in the cross-protection against HPV infection and disease that has been reported for the current HPV vaccines.
PLoS ONE 05/2013; 8(5):e61825. DOI:10.1371/journal.pone.0061825 · 3.23 Impact Factor
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ABSTRACT: The immunostimulants 3-O-desacyl-4'-monophosphoryl lipid A (MPL) and the saponin QS-21 are part of licensed or candidate vaccines. MPL and QS-21 directly affect the innate immune response to orchestrate the quality and intensity of the adaptive immune response to the vaccine antigens. The combination of immunostimulants in different adjuvant formulations forms the basis of Adjuvant Systems (AS) as a way to promote appropriate protective immune responses following vaccination. MPL and aluminum salts are present in AS04, and both MPL and QS-21 are present in AS01 and AS02, which are liposome- and emulsion-based formulations, respectively. The recent clinical performance of AS01-, AS02- and AS04-adjuvanted vaccines will be discussed in the context of the diseases being targeted. The licensing of two AS04-adjuvanted vaccines and the initiation of Phase III trials with an AS01-adjuvanted vaccine demonstrate the potential to develop new or improved human vaccines that contain MPL or MPL and QS-21.
Expert Review of Vaccines 04/2011; 10(4):471-86. DOI:10.1586/erv.11.29 · 4.21 Impact Factor
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ABSTRACT: Human papilloma viruses are responsible for a large number of benign and malignant lesions of the skin. HPV 6 and 11 cause up to 90 % of condylomata. Almost each cervical cancer is associated with HPV. HPV 16 und 18 induce up to 70 % of cervical neoplasias. The vaccination against HPV is internationally implemented and should be applied to young girls aged 12 to 17 according to STIKO criteria. The vaccination may reduce the rate of cervical cancer by 70 % and the rate of cervical intraepithelial neoplasia by 50 %. Many studies demonstrated the efficacy and safetyness of both vaccines. Gardasil (®) offers protection against HPV 6, 11, 16 and 18, Cervarix (®) against HPV 16 and 18. Protection against condylomata is offered by the quadrivalent vaccine in 90 %. The bivalent vaccine has demonstrated type-specific protection against the five most frequent cancer inducing types (16, 18, 31, 33, 45). The production of VLPs is an innovative technology. A comparison of both vaccines, Cervarix (®) and Gardasil (®), showed a higher immunogenicity for Cervarix (®). In Germany the immunization rates are still low comparing to other countries. As a method for secondary prevention of cervical cancer the PAP smear is still an effective method.
DMW - Deutsche Medizinische Wochenschrift 05/2011; 136(20):1067-72. DOI:10.1055/s-0031-1275845 · 0.54 Impact Factor
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