Seroepidemiology as basis for design of a human papillomavirus vaccination program

Ryding, Janka; French, Katherine; Nauclér, Pontus; Barnabas, Ruanne V.; Garnett, Geoffrey P.; Dillner, Joakim

doi:10.1016/j.vaccine.2008.07.041

Cited by 24 publications

(19 citation statements)

References 50 publications

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“…For the age groups assessed, the prevalence of HPV 16 and 18 NAbs was consistent with EIA-based results reported by others (6,7,9,12,16). Since it has been reported that 50% to 60% of naturally infected individuals do not have detectable antibodies (2), it is likely that the number of individuals exposed to HPV 16 and 18 infections within our prenatal population may be twice as high.…”

supporting

confidence: 89%

Prevalence of Human Papillomavirus 16 and 18 Neutralizing Antibodies in Prenatal Women in British Columbia

Krajden

Karunakaran

et al. 2009

Clin Vaccine Immunol

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Human papillomavirus (HPV) type 16 and 18 neutralizing antibody (NAb) titers were measured in 1,020 prenatal women in British Columbia aged 15 to 39. HPV 16 and 18 NAbs were detected in 183/1,020 (17.9%) and 97/1,020 (9.5%), respectively, and 39 (3.8%) had NAbs to both types. Titers were similar across age strata.Measurement of type-specific antibody responses to human papillomavirus (HPV) is important for seroprevalence estimates and assessment of vaccine efficacy. Vaccine manufacturers have developed enzyme immunoassays (EIAs) targeting neutralizing epitopes (3, 10), but neutralizing antibody (NAb) tests could be a suitable alternative because they confirm blocking of infection of susceptible cells and they potentially measure antibodies to more epitopes than existing manufacturers' assays (13). Pseudovirus (PsV)-based NAb assays utilizing in vitro-generated HPV capsids containing a reporter plasmid have been described (1, 11). NAbs inhibit PsVs from infecting cells and from expressing the reporter plasmid product. For this study, we developed and validated a PsV NAb assay for HPV 16 and 18 and determined the seroprevalence among prenatal women in British Columbia (BC).HPV 16 and 18 PsVs were prepared as previously described (1), except that the reporter plasmid encoded red fluorescent protein (RFP) (11). Electron microscopic examination of the PsV preparations showed typical papillomavirus morphology. Bands at 55 kDa (capsid protein L1) and 70 kDa (capsid protein L2) were observed on Western blot analysis with rabbit antisera. Cesium chloride density gradient ultracentrifugation showed that over half of the PsV fraction had a buoyant density of approximately 1.34 g/ml, consistent with capsids containing DNA. PsVs were titrated in 293TT cells by monitoring the cultures for red fluorescent cells, with each fluorescent cell representing one infectious unit.NAb tests were performed as follows: sera were heated at 56°C for 30 min, and duplicate serial dilutions were prepared. Each serum dilution was mixed with 100 infectious units of the respective PsV and incubated for 1 h at 37°C, followed by transfer to 293TT cells on microtiter plates. Plates were incubated at 37°C and read after 4 to 6 days. The endpoint (100% neutralizing titer [NT 100 ]) was the highest dilution of serum which completely blocked cells displaying red fluorescence. Back-titrations of the PsV and serially diluted positive and negative serum controls were included in each run.For initial NAb test validation, five anti-HPV positive control sera (two against HPV 16, one against HPV 18, one against HPV 6, 11, 16, and 18, and one against HPV 6 and 11) and one anti-HPV negative control obtained from the National Institute for Biological Standards and Control (NIBSC), United Kingdom, were titrated. NAb titers corresponded with known antibody status (Table 1), although some were near the assay cutoff (1:40). Control sera for routine use were obtained from a volunteer 1 month after receiving a full course of Gardasil vaccine and from an HPV 16-and 18-s...

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supporting

confidence: 89%

Prevalence of Human Papillomavirus 16 and 18 Neutralizing Antibodies in Prenatal Women in British Columbia

Krajden

Karunakaran

et al. 2009

Clin Vaccine Immunol

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“…After these assays have been completed, the early pregnancy sample was typically discarded. However, since the introduction of quality-controlled biobanking, the samples have been stored at -20°C in the SSM-Biobank (29).…”

Section: Discussionmentioning

confidence: 99%

“…Early pregnancy serum samples (gestational weeks 10-16) were retrieved from the Southern Sweden Microbiological Biobank (SSM-Biobank) (22). The SSM-Biobank stores more than 120,000 public health test samples at -20°C, which were obtained between 1986 and 2006 from all pregnant mothers at their first visit to the prenatal care clinics in Skå ne (29). The blood sample taken at this occasion is mandatory, as every pregnant mother in Sweden is tested for syphilis, HIV, hepatitis B, and rubella virus antibodies.…”

Section: Study Populationmentioning

confidence: 99%

Seroconversion to Islet Autoantibodies After Enterovirus Infection in Early Pregnancy

et al. 2012

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Gestational enterovirus (EV) infections have been associated with an increased risk for type 1 diabetes in the offspring. We therefore analyzed non-diabetic mothers for EV exposure in early pregnancy in relation to type 1 diabetes HLA-DQ risk genotypes and seroconversion to islet autoantibodies during pregnancy. Non-diabetic mothers who had islet autoantibodies (n = 365) against glutamic acid decarboxylase (GADA), islet antigen-2 autoantibodies (IA-2A), or insulin autoantibodies (IAA), in early pregnancy and at delivery were compared to islet autoantibody-negative mothers (n = 1457) matched for age and sampling date. Mothers were genotyped for HLA-DQ and analyzed for both EV-RNA and EV-IgM. EV-IgM, but not EV-RNA, was detected during early pregnancy in 12% of islet autoantibody-positive mothers compared to 11% of the controls. In early pregnancy, mothers with HLA-DQ 2/2 or 2/X genotypes showed an increased risk for islet autoantibodies at delivery (OR 1.85; p = 0.001). After adjusting for parity, maternal age, year of birth, and season of early pregnancy, early pregnancy EV-IgM combined with DQ2/2 or 2/X increased the risk for islet autoantibodies (OR 3.10; 95% CI 1; p = 0.008). EV-IgM in early pregnancy increased the risk for islet autoantibodies at delivery in non-diabetic mothers with HLA-DQ 2/2 or 2/X type 1 diabetes risk genotypes.

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“…Men may be even less likely than women to mount a detectable antibody response (41). The specificity of IgG is considered to be high, based on the finding of very low rates of antibody detection in sexually inexperienced and monogamous adults and in children (19,42). We tested the samples for antibodies to HPV-16 using ELISA and Luminex methods.…”

Section: Discussionmentioning

confidence: 99%

“…HPV seropositivity is strongly associated with the lifetime number of sexual partners, both for women (17) and for men (18). Both women and men are usually HPV seronegative before initiation of sexual activity (19). Sensitivity for detection of current sexually acquired HPV infection is f50% to 60% and the specificity is considered high (14).…”

Section: Introductionmentioning

confidence: 99%

Male Circumcision and Serologically Determined Human Papillomavirus Infection in a Birth Cohort

Dickson

Ryding

Roode

et al. 2009

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Circumcision has been reported to protect against infection with human papillomavirus (HPV) in men, but results have been inconsistent. We followed males in a birth cohort born in Dunedin, New Zealand, in 1972 and1973 from age 3 to 32 years. Seropositivity at age 32 years for the oncogenic types HPV-16 and 18, and the nononcogenic types 6 and 11, was studied in relation to maternal reports of circumcision status at age 3 for 450 men. Seropositivity to any of these types was associated with lifetime number of sexual partners (P = 0.03), and lower moral-religious emphasis of the family of origin (P < 0.001). Circumcision was not found to be protective, with the adjusted odds ratio (95% confidence interval) for HPV6/11/16/18 seropositivity among the circumcised compared with the uncircumcised being 1.4 (0.89-2.2).

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Seroepidemiology as basis for design of a human papillomavirus vaccination program

Cited by 24 publications

References 50 publications

Prevalence of Human Papillomavirus 16 and 18 Neutralizing Antibodies in Prenatal Women in British Columbia

Prevalence of Human Papillomavirus 16 and 18 Neutralizing Antibodies in Prenatal Women in British Columbia

Seroconversion to Islet Autoantibodies After Enterovirus Infection in Early Pregnancy

Male Circumcision and Serologically Determined Human Papillomavirus Infection in a Birth Cohort

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