Human Papillomavirus Antibody Reference Reagents for Use in Postvaccination Surveillance Serology

Centre for Infections, Health Protection Agency, London, United Kingdom.
Clinical and vaccine Immunology: CVI (Impact Factor: 2.47). 03/2012; 19(3):449-51. DOI: 10.1128/CVI.05641-11
Source: PubMed


Suitably controlled serosurveillance surveys are essential for evaluating human papillomavirus (HPV) immunization programs.
A panel of plasma samples from 18-year-old females was assembled, the majority of the samples being from recipients of the
bivalent HPV vaccine. Antibody specificities were evaluated by three independent laboratories, and 3 pools that displayed
no antibodies to any HPV type tested or intermediate or high levels of antibody to HPV16, HPV18, HPV31, and HPV45 were created.
These pools will be useful as control reagents for HPV serology.

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Available from: Elizabeth R Unger, Jan 06, 2014
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    • "Midpoint binding titers were estimated by interpolation. The high HPV16/18 and HPV negative plasma pools [27] were used as positive and negative serological control reagents, respectively. The high HPV16/18 reagent gave median (IQR) titers against the indicated HPV types as follows (n = 5): HPV16 69,124 (64,602–73,962), HPV18 41,211 (39,270–43,247), HPV31 2,655 (1,772–3,979) and HPV45 4,918 (4,452–5,432). "
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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. METHODS AND FINDINGS 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. CONCLUSIONS 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. TRIAL REGISTRATION NCT00956553.
    Preview · Article · May 2013 · PLoS ONE
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    ABSTRACT: We assessed HPV 16 and 18 antibody responses of female subjects enrolled in a 2- vs. 3-dose quadrivalent HPV (Q-HPV) vaccine trial ( NCT00501137) using the Merck competitive Luminex (cLIA) and total IgG Luminex (TIgG) immunoassays, and a pseudovirus neutralizing antibody (PsV NAb) assay. Subjects were enrolled in one of three groups: (1) 9-13yr, 2 doses of Q-HPV at 0, 6 months (n=259); (2) 9-13yr, 3 doses at 0, 2, 6 months (n=260); and (3) 16-26yr, 3 doses at 0, 2, 6 months (n=305). Sera were collected from all subjects at baseline, months 7 and 24, and from half the subjects at months 18 and 36. High correlation was observed between all three assays. At month 36, HPV 16 antibodies remained detectable in all subjects by all assays, whereas 86.4%, 99.6% and 100% of subjects respectively were HPV 18 cLIA, TIgG and PsV NAb (partial neutralization endpoint) seropositive. The proportion seropositive for HPV 18 by cLIA at 36 months was not significantly different for 2-dose girls vs. 3-dose adults (85.9% vs. 79.4%; p=0.51), whereas the proportion for 3-dose girls was significantly higher than for 3-dose adults (95.3% vs. 79.4%; p<0.01). The HPV 18 seropositive proportions by the TIgG and PsV NAb (partial neutralization endpoint) assays were the same for all subjects. High baseline HPV 16 and HPV 18 seropositivity was observed for the TIgG assay and it is unclear if all the detected TIgG antibodies are type-specific and/or neutralizing. For the PsV NAb assay, 90% and partial neutralization geometric mean titres were consistently 2-8-fold higher than for 100% neutralization, which enabled detection of HPV 18 NAb in subjects who lost detectable cLIA antibodies over time. We conclude that the PsV NAb assay is more sensitive than the cLIA, and likely more specific than the TIgG assay.
    Full-text · Article · Sep 2013 · Vaccine
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