Safety and immunogenicity of a 9-valent HPV vaccine in females 12–26 years of age who previously received the quadrivalent HPV vaccine

ObjectivesTo assess the safety and immunogenicity of the investigational 9-valent (6/11/16/18/31/33/45/52/58) HPV (9vHPV) vaccine in prior recipients of a 3-dose regimen of quadrivalent (6/11/16/18) HPV (qHPV) vaccine.MethodsV503-006 was a randomized, double-blinded, safety/tolerability and immunogenicity study of the 9vHPV vaccine in females 12–26 years of age who were previously vaccinated with qHPV vaccine. Subjects were randomized in a 2:1 ratio to receive 3 doses of 9vHPV vaccine (n = 618) or saline placebo (n = 306) at day 1, month 2, and month 6. Systemic, injection-site and serious adverse experiences (AEs) were monitored. Serum samples were collected at day 1, month 2, and month 7. Anti-HPV 6/11/16/18/31/33/45/52/58 titers were measured using the 9-valent HPV competitive Luminex Immunoassay (cLIA).ResultsThe frequency of injection-site AEs (days 1–5 following any vaccination) was higher in the 9vHPV vaccine group than in the placebo group (91.1% and 43.9%, respectively). The frequencies of vaccine-related systemic AEs (days 1–15 following any vaccination) were generally comparable between the 2 groups (30.6% in the 9vHPV vaccine group, and 25.9% in the placebo group). One vaccine-related serious AE was reported in each of the 9vHPV vaccine and placebo groups. Few subjects (9vHPV = 0.5%; placebo = 0%) discontinued due to an AE. At 4 weeks post-dose 3, over 98% of subjects in the 9vHPV vaccine group were seropositive for HPV types 31/33/45/52/58, with marked elevations in cLIA geometric mean titers (GMTs) to these HPV types. Anti-HPV 31/33/45/52/58 GMTs were lower than in subjects administered 9vHPV vaccine who had not previously received qHPV vaccine (based on cross-study analyses); the clinical significance of this difference is unknown.ConclusionsAdministration of a 3-dose regimen of 9vHPV vaccine to adolescent girls and young women 12–26 years of age who are prior qHPV vaccine recipients is highly immunogenic with respect to HPV types 31/33/45/52/58 and generally well tolerated.     

Antibody persistence and evidence of immune memory at 5 years following administration of the 9-valent HPV vaccine

BackgroundThe 9-valent HPV (9vHPV) vaccine was developed to prevent infection and disease related to 9 HPV types (HPV6/11/16/18/31/33/45/52/58) which cause approximately 90% of cervical cancers, HPV-related vulvar, vaginal and anal cancers, and genital warts worldwide. In a pivotal efficacy study, the 9vHPV vaccine prevented infection and disease due to the 9 vaccine types. Duration of protection remains to be determined. Vaccines that induce long-term protection are generally characterized by the generation of immune memory. The purpose of this report is to assess the persistence of HPV antibody response and existence of immune memory at 5 years post-vaccination.MethodsA subset of subjects (N = 150) who received 3 doses of 9vHPV vaccine at day 1, month 2 and month 6 in the pivotal efficacy study continued in a study extension and received a fourth dose of 9vHPV vaccine at month 60. Serum HPV antibody levels were measured pre-dose 4 and at 7 and 28 days post-dose 4 by competitive Luminex immunoassay. Adverse events were assessed using a vaccination report card.ResultsHPV antibodies induced following the 3-dose series of 9vHPV vaccine in the base study persisted through month 60 with seropositivity rates ranging from 77.5% to 100%. Geometric mean titers at 1 week and 1 month post-dose 4 were 1.25–4.10 and 1.65–4.88-fold higher, respectively, than levels observed 1 month following the completion of the three-dose primary series. Seropositivity rates were >99% and 100% at 1 week and 1 month post-dose 4, respectively. The fourth dose of 9vHPV vaccine was generally well tolerated.ConclusionsA three-dose regimen of the 9vHPV vaccine induced persistent HPV antibody response through 5 years post-vaccination. Administration of a fourth dose resulted in a strong anamnestic response to all 9 vaccine types. These findings suggest that the efficacy of the 9vHPV vaccine will be long lasting.Clinical Trials.gov Identifier: NCT00543543.     

Antibody responses among adolescent females receiving the quadrivalent HPV vaccine series corresponding to standard or non-standard dosing intervals

Quadrivalent human papillomavirus vaccine (HPV4) is recommended as a 3-dose series administered at 0, 1–2, and 6 months. However, this dosing schedule is often not followed leading to longer dosing intervals. We conducted a prospective study to assess antibody titers to HPV4 when dose 2 and/or dose 3 were administered on schedule or delayed. Healthy females (N = 331) aged 9–18 years were enrolled at the time of receipt of HPV4 dose 2 or 3. Participants were classified as belonging to one of four groups depending upon timing of receipt of HPV4: both doses on time; only dose 2 delayed later than 90 days; only dose 3 delayed later than 180 days; or both doses 2 and 3 delayed. Pre- and post-dose 3 blood samples were assayed for HPV antibody titers (types 6, 11, 16, and 18). Post-dose 3 geometric mean titers (GMTs) for all HPV types were not significantly lower for any of the delayed dosing groups when compared to the on time group. When compared to the on time group, the post dose 3 GMTs in the delayed dose 3 group were significantly higher (p < 0.05) for HPV types 6, 11, and 16. Our findings suggest that delays of dose 2 or 3 do not interfere with immune responses after completion of the 3-dose series. These results support current recommendations to not administer additional doses of HPV4 vaccine if dose 2, dose 3, or both doses have been administered late.     

Breastfeeding linked to the reduction of both rotavirus shedding and IgA levels after Rotarix® immunization in Mexican infants

We examined potential risk factors on vaccine virus shedding and antibody seroresponse to human rotavirus vaccine (Rotarix) in Mexican infants. Two doses of Rotarix were administered to infants during the first two visits for their routine childhood immunization (∼8 and 15 weeks of age) in Mexico City. Infant’s characteristics and socioeconomic indicators were obtained, including history of long-term feeding practices (exclusively/predominantly breastfed and exclusively/predominantly non-breastfed). Two serum specimens were collected, one during the second rotavirus vaccine visit and one 7 weeks later. Stool specimens were collected between days 4–7 after each of the two rotavirus vaccine doses. Rotavirus IgA and IgG titers in serum were determined by enzyme immunoassays (EIA) and rotavirus shedding in stool was assessed by EIA and confirmed by RT-PCR.The overall rotavirus IgA geometric mean titers (GMT) increased significantly post dose 2 from post dose 1 [176 (95%CI: 113–273) to 335 (238–471); p = 0.020). Infants who were exclusively/predominantly breastfed were less likely to shed vaccine virus in stool than those who were formula-fed (22% vs. 43%, p = 0.016). Infants who were breastfed had lower rotavirus IgA titers than those who were formula-fed after dose 1 [GMT: 145 (84–250) vs. 267 (126–566) p = 0.188] and dose 2 [236 (147–378) vs.578 (367–910), p = 0.007]. Infants who shed vaccine virus post dose 1 had significantly higher serum IgA GMT than those who did not shed [425 (188–965) vs. 150 (84–266), p = 0.038]. Breastfeeding was linked with the reduction of both stool vaccine shedding, and IgA seroresponse. The reduced rotavirus replication in the gut and shedding after dose 1 may explain in part the lower IgA response in serum.     

Factors related to vaccine uptake by young adult women in the catch-up phase of the National HPV Vaccination Program in Australia: Results from an observational study

BackgroundAustralia commenced a publically-funded, National Human Papillomavirus (HPV) Vaccination Program in 2007 with a two year catch-up phase for females aged 12–26 years.ObjectiveTo identify the factors associated with the uptake of the HPV vaccine (which has a recommended 3-dose schedule in Australia) by young adult women vaccinated by general practitioners and community-based programs within the catch-up phase.Methods1139 women who were eligible to receive the free HPV vaccine during the catch-up period were recruited in 2008–2009 (age 20–29 years at recruitment), in New South Wales, after having a normal (negative) cervical smear result recorded on the NSW Pap Test Register. Participants completed a self-administered questionnaire providing information on vaccination status, and sociodemographic and other factors.ResultsOverall, 880 (77%) women reported receiving ≥1 dose of the vaccine and 777 women (68%) reported receiving ≥2 doses. In multivariable analysis (adjusting for the period for which each woman was eligible for free HPV vaccination), uptake of ≥1 dose of the vaccine was significantly associated with being born in Australia (p < 0.01), being single (p = 0.02), being nulliparous (p < 0.01), living in a higher socioeconomic status area (p-trend = 0.03), living in more remote areas (p = 0.03), drinking alcohol (p < 0.01) and using hormonal contraceptives (p < 0.01). Although vaccinated women were more likely to have fewer sexual partners than unvaccinated women (p-trend = 0.02), they were also more likely to report a prior sexually transmitted infection (STI) (p = 0.03). Similar factors were associated with receiving ≥2 doses.ConclusionsIn this group, women living in higher socioeconomic status areas were more likely to be vaccinated against HPV in the catch-up phase of the national program. Although vaccinated women tended to have fewer sexual partners, they also reported prior STIs, which may be a marker of increased risk of prior exposure to HPV. The findings of this study reinforce the continuing need to prioritise equitable delivery of vaccination to various population subgroups.     

Clinician knowledge,clinician barriers,and perceived parental barriers regarding human papillomavirus vaccination: Association with initiation and completion rates

PurposeWe tested the hypothesis that clinician knowledge, clinician barriers, and perceived parental barriers relevant to the human papillomavirus (HPV) vaccination account for the variation in vaccine delivery at the practice-site level.MethodsWe conducted a survey from October 2015 through January 2016 among primary care clinicians (n = 280) in a 27-county geographic region to assess clinician knowledge, clinician barriers, and perceived parental barriers regarding HPV vaccination. Primary care clinicians included family medicine physicians, general pediatricians, and family and pediatric nurse-practitioners. We also used the Rochester Epidemiology Project to measure HPV vaccination delivery. Specifically we used administrative data to measure receipt of at least one valid HPV vaccine dose (initiation) and receipt of three valid HPV vaccine doses (completion) among 9–18 year old patients residing in the same 27-county geographic region. We assessed associations of clinician survey data with variation in vaccine delivery at the clinical site using administrative data on patients aged 9–18 years (n = 68,272).ResultsConsistent with our hypothesis, we found that greater knowledge of HPV and the HPV vaccination was associated with higher rates of HPV vaccination initiation (Incidence rate ratio [IRR] = 1.05) and completion of three doses (IRR = 1.28). We also found support for the hypothesis that greater perceived parental barriers to the HPV vaccination were associated with lower rates of initiation (IRR = 0.94) and completion (IRR = 0.90). These IRRs were statistically significant even after adjustment for site-level characteristics including percent white, percent female, percent ages 9–13, and percent with government insurance or self-pay at each site.ConclusionsClinician knowledge and their report of the frequency of experiencing parental barriers are associated with HPV vaccine delivery rates—initiation and completion. Higher measures of knowledge correlated with higher rates. Fewer perceived occurrences of parental barriers correlated with lower rates. These data can guide efforts to improve HPV vaccine delivery in clinical settings.     

Natural acquired group B Streptococcus capsular polysaccharide and surface protein antibodies in HIV-infected and HIV-uninfected children

Group B Streptococcus (GBS) is a major cause of invasive disease in young infants and also in older immunocompromised individuals, including HIV-infected persons. We compared naturally acquired antibody titres to GBS polysaccharide and surface protein antigens in HIV-uninfected and HIV-infected children aged 4–7 years.A multiplex Luminex immunoassay was used to measure IgG concentrations against GBS capsular polysaccharides (CPS) for serotypes Ia, Ib, III and V; and also extracellular localizing proteins which included cell-wall anchored proteins: Fibrinogen binding surface Antigen (FbsA), GBS Immunogenic Bacterial Adhesin (BibA), Surface immunogenic protein (Sip), gbs0393, gbs1356, gbs1539, gbs0392; and lipoproteins gbs0233, gbs2106 and Foldase PsrA.HIV-infected children (n = 68) had significantly lower IgG GMT compared to HIV-uninfected (n = 77) children against CPS of serotype Ib (p = 0.012) and V (p = 0.0045), and surface proteins Sip (p < 0.001) and gbs2106 (p = 0.0014). IgG GMT against GBS surface proteins: FbsA, gbs1539, gbs1356, gbs0392, gbs0393 and Foldase PsrA were significantly higher in HIV-infected children (p < 0.004). Moreover, amongst HIV infected children, IgG GMT to GBS surface proteins were higher in those with CD4⁺ lymphocyte counts <500 cell/μL compared to those who had CD4⁺ lymphocyte count ⩾500 cell/μL with the exception of Sip.The increased susceptibility to invasive GBS disease in HIV-infected individuals could be due to the lower serotype specific capsular antibody and possibly due to lower antibody to some of the GBS proteins such as Sip and gbs2106.     

Immunogenicity and safety of an E. coli-produced bivalent human papillomavirus (type 16 and 18) vaccine: A randomized controlled phase 2 clinical trial

BackgroundThis study aimed to investigate the dosage, immunogenicity and safety profile of a novel human papillomavirus (HPV) types 16 and 18 bivalent vaccine produced by E. coli.MethodsThis randomized, double-blinded, controlled phase 2 trial enrolled women aged 18–25 years in China. Totally 1600 eligible participants were randomized to receive 90 μg, 60 μg, or 30 μg of the recombinant HPV 16/18 bivalent vaccine or the control hepatitis B vaccine on a 0, 1 and 6 month schedule. The designated doses are the combined micrograms of HPV16 and 18 VLPs with dose ratio of 2:1. The immunogenicity of the vaccines was assessed by measuring anti-HPV 16 and 18 neutralizing antibodies and total IgG antibodies. Safety of the vaccine was assessed.ResultsAll but one of the seronegative participants who received 3 doses of the HPV vaccines seroconverted at month 7 for anti-HPV 16/18 neutralizing antibodies and IgG antibodies. For HPV 16, the geometric mean titers (GMTs) of the neutralizing antibodies were similar between the 60 μg (GMT = 10,548) and 90 μg (GMT = 12,505) HPV vaccine groups and were significantly higher than those in the 30 μg (GMT = 7596) group. For HPV 18, the GMTs of the neutralizing antibodies were similar among the 3 groups. The HPV vaccine was well tolerated. No vaccine-associated serious adverse events were identified.ConclusionThe prokaryotic-expressed HPV vaccine is safe and immunogenic in women aged 18–25 years. The 60 μg dosage formulation was selected for further investigation for efficacy.Clinical trials registration: NCT01356823.     

Association of both consistency and strength of self-reported clinician recommendation for HPV vaccination and HPV vaccine uptake among 11- to 12-year-old children

PurposeWe tested the hypotheses that consistency and strength of clinician recommendation of the human papillomavirus (HPV) vaccination would be associated with vaccine delivery rates.MethodsFrom October 2015 through January 2016, we conducted a survey of primary care clinicians (n = 227) in Southeastern Minnesota to evaluate clinician behaviors regarding HPV vaccination. The survey response rate was 41.0% (51 clinical sites). We used the Rochester Epidemiology Project, a clinical data linkage infrastructure, to ascertain clinical site-level HPV vaccination rates. We examined associations of clinician self-reports of both the consistency and strength of their recommendations for HPV vaccination for patients aged 11–12 years (n = 14,406) with site-level vaccination rates.ResultsThe majority of clinicians reported consistently (always or usually) recommending the HPV vaccine to females (79.0%) and to males (62.2%); 71.9% of clinicians reported strongly recommending the vaccine to females while 58.6% reported strongly recommending to males. Consistency and strength of recommending the HPV vaccine was significantly higher among those practicing in pediatrics and board certified in pediatrics compared to family medicine. Higher rates of initiation (1 dose) [Incidence Rate Ratio (IRR) = 1.05; 95% CI (1.01–1.09)] and completion (3 doses) [IRR = 1.08; 95% CI (1.02–1.13)] were observed among clinical sites where, on average, clinicians more frequently reported always or usually recommending the vaccine for females compared to sites where, on average, clinicians reported recommending the vaccine less frequently. Similarly, higher rates of initiation [IRR = 1.03; 95% CI (1.00–1.06)] and completion [IRR = 1.04; CI (1.00, 1.08)] were observed among sites where clinicians reported strongly recommending the vaccine to females more frequently compared to sites where, on average, clinicians reported strongly recommending the HPV vaccine less frequently; similar associations were observed for male initiation [IRR = 1.05; CI (1.02,1.08)] and completion [IRR = 1.05; 95% CI (1.01, 1.09)].ConclusionsConsistency and strength of HPV vaccination recommendation was associated with higher vaccination rates.     

The safety and immunogenicity of Quadrivalent HPV (qHPV) vaccine in systemic lupus erythematosus

ObjectiveThis study evaluated the safety and immunogenicity of qHPV vaccine in SLE.MethodsSubjects: 34 women ages 19–50 years (yrs.) with mild to moderate SLE & minimally active or inactive SLE received qHPV vaccine at the standard dosing schedule.Exclusion criteria: active SLE disease (SELENA-SLEDAI > 2), history of severe SLE disease, deep venous thrombosis, on >400 mg/day of hydroxychloroquine, on >15 mg/day of prednisone, or active infections. Patients were monitored for adverse events (AE), SLE flare, generation of thrombogenic antibodies and thrombosis. Antibody (Ab) levels to HPV 6, 11, 16 & 18 were measured by HPV competitive Luminex Immunoassay and Geometric Mean Titers (GMTs) were calculated for each HPV type. Seroconversion was assessed for those seronegative at baseline.ResultsThe women in the study: African-American (79%), mean age = 38.1 years, mean age at diagnosis of SLE = 28.6 years, 35.3% had a history of smoking, 91% had 4 or more sexual partners, 50% had a history of sexually transmitted diseases, and 27.3% used condoms on a regular basis. Vaccine site reactions (VSRs) occurred in 62%, all mild. Ninety-seven percent experienced at least 1 non vaccine adverse event (nvAE) with a total of 493 nvAEs in 33 patients, of which 90% were mild and none were related to vaccine or SLE. There were 9 serious AEs, none were related to vaccine or SLE, all resolved. No patient experienced an SLE flare, thrombosis, or generation of thrombogenic antibodies. Seroconversion rate was 100% with mean GMTs comparable to Gardasil® package insert data.ConclusionIn this SLE vaccine study, qHPV vaccine was generally safe, well tolerated, and highly immunogenic.This clinical trial is registered on Clinical Trials.gov under number, NCT01741012 and was conducted under the FDA IND BB14113.     

A phase III clinical study to compare the immunogenicity and safety of the 9-valent and quadrivalent HPV vaccines in men

BackgroundA nine-valent human papilloma virus (9vHPV) vaccine has been developed to prevent infections and diseases related to HPV 6/11/16/18 (as per the licensed quadrivalent HPV (qHPV) vaccine) as well as to five additional oncogenic HPV types (HPV 31/33/45/52/58). The 9vHPV vaccine has the potential to prevent 90% of cervical cancers, HPV-related anal, vaginal and vulval cancers and anogenital warts. We compared the immunogenicity and safety of the 9vHPV vaccine versus the qHPV vaccine in 16–26-year-old men.MethodsParticipants (N = 500) were randomised to receive 9vHPV or qHPV vaccines on day 1, month 2 and month 6. Serology testing was performed on day 1 and month 7. HPV type-specific antibody titres (anti-HPV 6/11/16/18/31/33/45/52/58) were determined by competitive Luminex immunoassay and expressed as geometric mean titres and seroconversion rates. Vaccine safety was also assessed.ResultsThe HPV 6/11/16/18 immune responses elicited by the 9vHPV vaccine were comparable with those elicited by the qHPV vaccine. All participants receiving the 9vHPV vaccine seroconverted for HPV 31/33/45/52/58. The 9vHPV and qHPV vaccines showed comparable safety profiles.ConclusionsIn addition to immune responses to HPV 31/33/45/52/58, a three-dose regimen of the 9vHPV vaccine elicited a similar immune response to HPV 6/11/16/18 when compared with the qHPV vaccine in men aged 16–26 years. The safety profile was also similar for the two vaccines. The results from this study support extending the efficacy findings with qHPV vaccine to 9vHPV vaccine in men aged 16–26 years.NCT02114385     

HPV vaccine for teen boys: Dyadic analysis of parents' and sons' beliefs and willingness

ObjectiveParents and adolescents often decide together whether the child should receive human papillomavirus (HPV) vaccine. However, few studies have investigated the dyadic nature of beliefs that affect this process.MethodData came from the 2010 HPV Immunization in Sons (HIS) Study, a national sample of 412 parents and their adolescent sons. We conducted dyadic multivariate logistic regression to examine the relationships between parents' and sons' HPV vaccine beliefs and their willingness to have the son receive the vaccine.ResultsLess than half of parents and sons were willing to have the sons receive HPV vaccine (43% and 29%, respectively). Willing parents and sons anticipated greater regret if the son did not receive HPV vaccine but later contracted an HPV infection (parent odds ratio [OR] = 1.72, 95% confidence interval [CI] = 1.24–2.40; son OR = 1.51, 95% CI = 1.04–2.19) (both p < .05). Lower concerns about side effects, such as pain and fainting, were also associated with willingness.ConclusionParents and sons were more willing to have the son receive HPV vaccine if they had higher anticipated regret about potential HPV infection and lower concerns about side effects. Communication campaigns may be able to target these beliefs to increase parents' and sons' willingness to seek HPV vaccination.     

A Phase 2 randomized,observer-blind,placebo-controlled,dose-ranging trial of aluminum-adjuvanted respiratory syncytial virus F particle vaccine formulations in healthy women of childbearing age

ObjectiveRespiratory syncytial virus (RSV) causes significant morbidity and mortality in infants. We are developing an RSV fusion (F) protein nanoparticle vaccine for immunization of third trimester pregnant women to passively protect infants through transfer of RSV-specific maternal antibodies. The present trial was performed to assess the immunogenicity and safety of several formulations of RSV F vaccine in 1-dose or 2-dose schedules.MethodsPlacebo, or vaccine with 60 μg or 120 μg RSV F protein and 0.2, 0.4, or 0.8 mg aluminum, were administered intramuscularly on Days 0 and 28 to healthy women 18–35 years old. Immunogenicity was assessed from Days 0 through 91 based on anti-F IgG and palivizumab-competitive antibody (PCA) by ELISA, and RSV A and B neutralizing antibodies by microneutralization (MN) assay. Solicited adverse events were collected through Day 7 and unsolicited adverse events through Day 91.ResultsAll formulations were well-tolerated, with no treatment-related serious adverse events. Anti-F IgG and PCA responses were correlated and increased after both doses, while MN increased significantly only after the first dose, then plateaued. The timeliest and most robust antibody responses followed one dose of 120 μg RSV F protein and 0.4 mg aluminum, but persistence through 91 days was modestly (∼25%) superior following two doses of 60 μg RSV F protein and 0.8 mg aluminum. Western blot analysis showed RSV infections in active vaccinees were reduced by 52% overall (p = 0.009 overall) over the Day 0 through 90 period.ConclusionsRSV F nanoparticle vaccine formulations were well tolerated and immunogenic. The optimal combination of convenience and rapid response for immunization in the third trimester occurred with 120 μg RSV F and 0.4 mg aluminum, which achieved peak immune responses in 14 days and sufficient persistence through 91 days to allow for passive transfer of IgG antibodies to the fetus. NCT01960686.     

The number of injected same-day preschool vaccines relates to preadolescent needle fear and HPV uptake

PurposeFear of needles develops at approximately five years of age, and decreases compliance with healthcare. We sought to examine the relationship of preschool vaccine history, parent and preadolescent needle fear, and subsequent compliance with optional vaccines.MethodsAs part of a private practice randomized controlled trial, parents and 10–12 year olds rated needle anxiety on a 100 mm visual analog scale. This follow-up cohort study compared their needle anxiety to previous vaccination records, including number of vaccinations between ages four and six years (total and same-day maximum), and subsequent initiation of the HPV vaccine through age 13.ResultsOf the 120 preadolescents enrolled between 4.28.09 and 1.19.2010, 117 received preschool vaccinations between ages four and six years. The likelihood of being in the upper quartile of fear (VAS ≥ 83) five years later increased with each additional same-day injection (OR = 3.108, p = 0.0100 95%CI = 1.311, 7.367), but was not related to total lifetime or total four-to-six year injections. Only 12.5% (15) of parents reported anxiety about their preadolescents’ vaccines (VAS > 50). Parent and child anxiety was weakly correlated (r = 0.15). Eight children in the upper fear quartile began their HPV series (26.67%) compared to 14 in the lower quartile (48.28% VAS < 32) (OR 2.57, p = 0.0889, 95%CI 0.864–7.621); there was no difference in HPV uptake between upper and lower quartile of parent anxiety.ConclusionsThe more same-day preschool injections between 4 and 6 years of age, the more likely a child was to fear needles five years later. Preadolescent needle fear was a stronger predictor than parent vaccine anxiety of subsequent HPV vaccine uptake.     

Assessment of HPV 16 and HPV 18 antibody responses by pseudovirus neutralization,Merck cLIA and Merck total IgG LIA immunoassays in a reduced dosage quadrivalent HPV vaccine trial

We assessed HPV 16 and 18 antibody responses of female subjects enrolled in a 2- vs. 3-dose quadrivalent HPV (Q-HPV) vaccine trial (ClinicalTrials.gov 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) 9–13 yr, 2 doses of Q-HPV at 0, 6 months (n = 259); (2) 9–13 yr, 3 doses at 0, 2, 6 months (n = 260); and (3) 16–26 yr, 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.     

Persistence of bactericidal antibodies following booster vaccination with 4CMenB at 12, 18 or 24 months and immunogenicity of a fifth dose administered at 4 years of age-a phase 3 extension to a randomised controlled trial

Background4CMenB is immunogenic in infants and toddlers. We assessed persistence of human complement serum bactericidal activity (hSBA) following a fourth dose administered at 12, 18 or 24 months and characterised the antibody response to a fifth dose administered at 4 years of age.MethodsA phase 3, open label, multi-centre extension to a randomised controlled trial (ClinicalTrials.gov identifier NCT01717638) conducted in four countries (number of centres): Czech Republic (nineteen), Italy (four), Spain (four) and the United Kingdom (four). Four-year-old children who were either 4CMenB-naïve or had previously received a variety of 3-dose infant priming schedules and a booster vaccine as toddlers (follow-on group) were recruited. Venous blood samples were obtained to determine hSBA against four reference strains; acting as targets to assess immunity to each of the vaccine antigens, NadA (5/99), fHbp (H44/76), PorA (NZ98/254), and NHBA (M10713) at baseline (prior to vaccination, all participants) and one month following a dose of 4CMenB for all vaccine-naïve and follow-on participants primed with the 2, 3, 4 schedule, and a third of follow-on participants primed with a 2, 4, 6 month schedule.ResultsAt baseline (prior to vaccination), the proportion of participants (n = 468) with hSBA titers ⩾ 5 was similar across all followon groups: 89–100% against 5/99; 12–35% for H44/76; 8–12% for NZ98/254 and 53–80% for M10713 compared with 5%, 0%, 0%; and 60% respectively, for the vaccine-naïve controls (n = 206). Following a dose of 4CMenB at 4 years of age, this increased to 100% (5/99), 97–100% (H44/76), 80–95 % (NZ98/254) and 84–100% (M10713) (n = 210), compared with 89%, 70%, 24%, and 76% respectively for vaccine-naïve controls (n = 192).ConclusionWaning of protective antibodies occurred 12–36 months after toddler booster regardless of age at boost. This was least marked against target strains 5/99 and M10713. A robust memory response occurred after a booster dose given at 4 years of age.     

Association between mother-child sexual communication and HPV vaccine uptake

ObjectiveTo examine the association between mother-child communication about sex, sexually transmitted diseases (STDs), and contraception/condoms and HPV vaccine uptake by gender.MethodsWomen (n = 1372) with ≥ 1 child aged 9–17 years receiving care in reproductive health clinics in Southeast Texas were asked to complete a self-administered questionnaire between September 2011 and October 2013.ResultsThe majority of mothers with ≥ 1 eligible daughter (n = 886) reported having talked about ‘sex’ (77.7%), ‘STDs’ (76.6%) and ‘contraception’ (73.2%) with their daughters. The respective figures for mothers with ≥ 1 son (n = 836) were 68.8%, 69.0% and 65.3%. Mothers who discussed sex, STDs, or contraception with their daughters compared to those who did not were more likely to report that their daughter initiated (≥ 1 dose) HPV vaccination after adjusting for confounders (all p < .05). Similarly, mother–son discussions about STDs or condoms, but not sex, were associated with HPV vaccine initiation for their sons compared to those who did not discuss these topics. These associations were not significant with regard to HPV vaccine completion (3 doses) for neither daughters nor sons.ConclusionMother–child communication on STDs and contraception/condoms is associated with HPV vaccine initiation, but not completion, among both daughters and sons.     

Immunogenicity and persistence of immunity of a quadrivalent Human Papillomavirus (HPV) vaccine in immunocompromised children

AimThe aim of this study was to determine the immunogenicity and reactogenicity of HPV vaccine in immunocompromised children.MethodsA multi-centre clinical trial was conducted in three paediatric hospitals in Australia. Unvaccinated children 5–18 years of age attending one of three paediatric hospitals with a range of specified conditions associated with immunosuppression were included. Quadrivalent HPV vaccine (Gardasil) was given to the participants and serum anti-HPV antibody levels were measured at baseline (before first dose), 7 and 24 months after the first dose of vaccine.ResultsFifty-nine participants were enrolled across the three paediatric hospitals and among those one was seropositive to types 6, 11 and 16 at baseline. Seven months after the first dose, seroconversion rates were 93.3%, 100%, 100% and 88.9% for type 6, 11, 16 and 18 respectively. The corresponding rates at 24 month follow up were 82.2%, 91.1%, 91.1% and 68.9%. The greatest increase in geometric mean titre (GMT) was for type 16, followed by type 11. GMTs declined over the following months, but remained more than fourfold higher for all serotypes compared to baseline titres at 24 months post vaccination. Injection site erythema, pain and swelling were commonly reported local adverse events and were less common after each dose. Few participants reported systemic adverse events, and minor disease flare occurred in two participants. One child developed a squamous cell oral carcinoma during follow up, but tissue was unable to be tested for HPV.ConclusionImmunosuppressed children had an adequate immunogenic response to Quadrivalent HPV vaccine regardless of age and the cause of immunosuppression. HPV related cancers occur at higher frequency and earlier in immunosuppressed patients, so early vaccination and optimal scheduling should be further studied in such children.Clinical trial registration: NCT02263703 (ClinicalTrials.gov)     

Immunity to hepatitis A and B persists for at least 15 years after immunisation of adolescents with a combined hepatitis A and B vaccine

BackgroundThe exact duration of antibody persistence to hepatitis A and B and the need for booster dosing following primary immunisation remains undefined. A long-term study was designed to follow antibody persistence and immune memory on an annual basis for up to 15 years following vaccination during adolescence.MethodsSubjects received a combined hepatitis A and B vaccine (Twinrix™, GSK Vaccines, Belgium) at 12–15 years of age, either as 2-dose of the adult formulation or 3-dose of the paediatric formulation. Blood samples were taken every year thereafter to assess antibody persistence and immune memory to hepatitis A and B. Antibodies to hepatitis A virus (anti-HAV) and hepatitis B surface antigen (anti-HBs) were measured at Years 11–15. At Year 15 immune memory was further assessed by measuring the anamnestic response to a challenge dose of the monovalent vaccine, which was administered to subjects whose antibody concentrations fell below the pre-defined cut-offs (anti-HAV: <15 mIU/mL; anti-HBs: <10 mIU/mL).Results209 subjects returned for follow-up at Year 15 of whom 162 were included in the long-term according-to-protocol immunogenicity cohort. All subjects remained seropositive for anti-HAV antibodies, while 81.1% and 81.8% still had anti-HBs antibodies ≥10 mIU/mL in the 2- and 3-dose groups, respectively. Following hepatitis B vaccine challenge dose administration to 19 subjects, all except one in the 3-dose group, mounted a robust anamnestic response. The safety and reactogenicity profile of the hepatitis B challenge was consistent with previous experience.ConclusionImmunity to hepatitis A and B persists 15 years after adolescent vaccination with a combined hepatitis A and B vaccine. Highly effective anamnestic response indicates that a booster dose should not be required for 15 years after primary vaccination.Trial registrationhttp://www.clinicaltrials.gov NCT00875485.