Human papillomavirus prevalence and risk factors among Australian women 9–12 years after vaccine program introduction

BackgroundIn Australia, high and widespread uptake of the quadrivalent human papillomavirus (HPV) vaccine has led to substantial population-level reductions in the prevalence of quadrivalent vaccine targeted HPV genotypes 6/11/16/18 in women aged ≤ 35 years. We assessed risk factors for HPV detection among 18–35 year old women, 9–12 years after vaccine program introduction.MethodsWomen attending health services between 2015 and 2018 provided a self-collected vaginal specimen for HPV genotyping (Roche Linear Array) and completed a questionnaire. HPV vaccination status was validated against the National Register. Adjusted odds ratios (aORs) and 95% confidence intervals (CI) were calculated for factors associated with HPV detection.ResultsAmong 1564 women (median age 24 years; IQR 21–27 years), Register-confirmed ≥ 1-dose vaccine coverage was highest at 69.3% and 68.1% among women aged 18–21 and 22–24 years respectively, decreasing to 42.9% among those aged 30–35 years. Overall prevalence of quadrivalent vaccine-targeted HPV types was very low (2.0%; 95% CI: 1.4–2.8%) and influenced only by vaccination status (5.5% among unvaccinated compared with 0.7% among vaccinated women; aOR = 0.13 (95% CI: 0.05–0.30)). Prevalence of remaining HPV types, at 40.4% (95% CI: 38.0–42.9%), was influenced by established risk factors for HPV infection; younger age-group (p-trend < 0.001), more recent (p < 0.001) and lifetime sexual partners (p-trend < 0.001), but not vaccination status. Prevalence of HPV31/33/45, which shared risk factors with that of non-vaccine targeted HPV types, was also lower among vaccinated (4%) compared with unvaccinated (7%) women (aOR = 0.51; 95% CI: 0.29–0.89), indicative of cross-protection.ConclusionVaccination has changed the epidemiology of HPV infection in Australian women, having markedly reduced the prevalence of vaccine-targeted types, including amongst women with known risk factors for infection. Vaccinated women appear to be benefiting from modest cross-protection against types 31/33/45 afforded by the quadrivalent HPV vaccine. These results reinforce the importance of HPV vaccination.     

Well-woman visit of mothers and human papillomavirus vaccine intent and uptake among their 9–17 year old children

Objective

To examine the association between attending a well-woman clinic in the prior 2 years and obtaining the human papillomavirus (HPV) vaccine for their 9–17-year-old child.

Methods

Women (n = 1256) who attended reproductive health clinics during September 2011 to February 2013 and had ≥1 children 9–17 years of age were asked to complete a self-administered questionnaire containing questions on demographic characteristics, prior well-woman visits, HPV awareness, and HPV vaccine intent and uptake among their adolescent children.

Results

Nearly 78% of women reported having undergone a well-woman visit during the past 2 years. Bivariate analysis showed that the HPV vaccine initiation (23.9% vs. 14.0%, P = .004) and completion (13.6% vs. 6.7%, P = .011) among 9–17 daughters differed between mothers who did or did not have a well-woman visit during the past 2 years. However, intent to vaccinate them (47.2% vs. 53.3%, P = .173) did not differ between these two groups. With regard to 9–17 year old sons, vaccine initiation (10.1% vs. 9.6%, P = .871), completion (4.6% vs. 2.4%, P = .273) and intent to vaccinate (47.3% vs. 52.1%, P = .311) did not differ between these two groups. Multivariable logistic regression analyses confirmed the findings of these bivariate analyses after adjusting for confounder variables.

Conclusion

The well-woman visit may be a missed opportunity for physicians to educate their patients about the benefits of HPV vaccination for their adolescent children in general and sons in particular. Intervention studies are warranted to assess the benefits of using this setting to improve HPV vaccine uptake in the US.     

Factors affecting non-coverage of measles-rubella vaccination among children aged 9–59 months in Tanzania

Globally, measles remains a major cause of child mortality, and rubella is the leading cause of birth defects among all infectious diseases. In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan that set a target to eliminate Measles-Rubella (MR) in five of the six World Health Organization (WHO) regions by 2020. This was cross-sectional study employed both quantitative and qualitative research methods. The sample size was calculated to provide overall, age- and sex-specific coverage estimates for MR vaccine among children aged between 9 and 59 months at the national level. Using desired precision of ±5% with an expected coverage of 95%, a total of 15,235 households were required. The age of children, a child who had received the MR vaccine before the campaign, household wealth quintile, the age of caregivers, and their marital status were associated with non-coverage of MR vaccination among children aged 9–59 months in Tanzania. Nationally, an estimated 88.2% (95% CI: 87.3–89%) of children aged 9–59 months received the MR campaign dose, as assessed by caregivers’ recall. These estimates revealed slightly higher coverage in Zanzibar 89.6% (95% CI: 84.7–93%) compared to Mainland Tanzania 88.1% (95% CI 87.2–88.9%). These associated factors revealed causes of unvaccinated children and may be some of the reasons for Tanzania’s failure to meet the MR campaign target of 95 percent vaccination coverage. Thus, vaccine development must increase programmatic oversight in order to improve immunization activities and communication strategies in Tanzanian areas with low MR coverage.     

Antibody persistence of two pentavalent DTwP–HB–Hib vaccines to the age of 15–18 months,and response to the booster dose of quadrivalent DTwP–Hib vaccine

Objectives

Antibody persistence in children following three doses of primary vaccination with diphtheria, tetanus, whole-cell-pertussis (DTwP), hepatitis B, and Haemophilus influenzae type b (Hib) vaccines (SIIL Pentavac vaccine vs. Easyfive^® of Panacea Biotec), and response to the booster dose of DTwP–Hib (Quadrovax^®) vaccine.

Methods

Children who completed their primary immunization were assessed for antibodies at 15–18 months of age, and then given a booster dose of DTwP–Hib vaccine. Reactogenicity and safety of the booster dose was evaluated.

Results

Both pentavalent vaccines demonstrated a good immune response at 15–18 months. Following the booster dose, all vaccinated subjects achieved protective titers against diphtheria, tetanus and Hib, whereas the response to pertussis antigen was ∼78%. Fever and irritability was noted in 24%, local pain in 51%, and swelling in 36% of the children following booster dose.

Conclusions

Primary immunization with either pentavalent vaccine induced an excellent immunity lasting till the second year of life. A booster dose with DTwP–Hib (Quadrovax^®) vaccine effectuated a good anamnestic response to all vaccine components, being specially strong for Hib in children previously vaccinated with SIIL liquid pentavalent vaccine (Pentavac^®). Also, the safety profile of SIIL quadrivalent vaccine (Quadrovax^®) administered as booster dose was acceptable.     

Effect of number of human papillomavirus vaccine doses on guideline adherent cervical cytology screening among 19–26 year old females

PurposeLittle is known about how the number of HPV vaccine doses affect adherence to screening guidelines. This study compared adherence to cervical cancer screening by the number of HPV vaccine doses received by young women and assessed whether the specialty of vaccinating providers affected behavior.MethodsThis retrospective cohort study using administrative insurance claims records included 24,964 19–26 year old women who received at least 1 injection of the HPV vaccine between January 2006 and November 2009. Vaccinated young women continuously enrolled in a nationally-representative private insurance plan for 6 months prior to and 37 months after HPV vaccine administration were included. Logistic regression was used to compare the odds of Papanicolaou (Pap) testing 3 years after vaccine initiation by number of vaccine doses and provider type.ResultsIn this sample, 79.3% had a Pap test 3 years following vaccine initiation. Receiving 1 (aOR: 0.60, 95% CI 0.55–0.65) or 2 (aOR: 0.80, 95% CI 0.74–0.87) doses was associated with decreased odds of Pap testing compared to 3 doses. Many young women in our sample (16.5%) were diagnosed with cervical dysplasia prior to HPV vaccination. Patients vaccinated by non-obstetrician/gynecologists were less likely to get a Pap test following vaccination.ConclusionsWomen who received 1 or 2 doses of the HPV vaccine were less likely than those who received 3 doses to be screened for cervical cancer 3 years following vaccine initiation. Pediatricians and primary care physicians should convey the importance of initiating and continuing screening to HPV vaccinated patients.     

Safety of quadrivalent human papillomavirus vaccine (Gardasil®) in pregnancy: Adverse events among non-manufacturer reports in the Vaccine Adverse Event Reporting System, 2006–2013

BackgroundIn 2006, quadrivalent human papillomavirus (HPV4; Gardasil, Merck & Co., Inc.) vaccine was licensed in the US for use in females aged 9–26 years. HPV4 is not recommended during pregnancy; however, inadvertent administration during pregnancy may occur.ObjectivesTo evaluate and summarize reports to the Vaccine Adverse Event Reporting System (VAERS) in pregnant women who received HPV4 vaccine and assess for potentially concerning adverse events among non-manufacturer reports.MethodsWe searched the VAERS database for non-manufacturer reports of adverse events (AEs) in pregnant women who received HPV4 vaccine from 6/1/2006 to 12/31/2013. We conducted clinical review of reports and available medical records.ResultsWe found 147 reports after HPV4 vaccine administered to pregnant women. The most frequent pregnancy-specific AE was spontaneous abortion in 15 (10.2%) reports, followed by elective terminations in 6 (4.1%). Maternal fever was the most frequent non-pregnancy-specific AE in 3 reports. Two reports of major birth defects were received. No maternal deaths were noted. One hundred-three (70.1%) reports did not describe an AE.ConclusionsThis review of VAERS non-manufacturer reports following vaccination with HPV4 in pregnancy did not find any unexpected patterns in maternal or fetal outcomes.     

Immune non-interference and safety study of Vi-DT typhoid conjugate vaccine with a measles,mumps and rubella containing vaccine in 9–15 months old Nepalese infants

BackgroundTyphoid fever is a common disease in developing countries especially in the Indian subcontinent and Africa. The available typhoid conjugate vaccines (TCV) have been found to be highly immunogenic in infants and children less than 2 years of age. Many countries are planning to adopt TCV in their routine EPI programs around 9 months of age when measles containing vaccines are given. Therefore, Vi-DT TCV was tested in 9–15 months aged healthy infants in Nepal to demonstrate non-interference with a measles containing vaccine.MethodsThis was a randomized, open label, phase III study to assess the immune non-interference, safety, and reactogenicity of Vi-DT typhoid conjugate vaccine when given concomitantly with measles, mumps and rubella (MMR) vaccine. A total of 360 participants aged 9–15 months were enrolled and randomized equally into Vi-DT + MMR (180 participants) or MMR alone (180 participants) group and were evaluated for immunogenicity and safety 28 days post vaccination.ResultsUsing the immunogenicity set, difference between proportions (95% CI) of the Vi-DT + MMR group vs MMR alone group were ?2.73% (-8.85, 3.38), ?3.19% (-11.25, 4.88) and 2.91% (-3.36, 9.18) for sero-positivity rate of anti-measles, anti-mumps and anti- rubella, respectively. Only the lower bound of the range in difference of the proportions for sero-positivity rate of anti-mumps did not satisfy the non-inferiority criteria as it was above the ?10% limit, which may not be of clinical significance. These results were confirmed in the per protocol set. There were no safety concerns reported from the study and both Vi-DT + MMR and MMR alone groups were comparable in terms of solicited and unsolicited adverse events .ConclusionsResults indicated that there is non-interference of MMR vaccine with Vi-DT and Vi-DT conjugate vaccine could be considered as an addition to the EPI schedule among children at risk of contracting typhoid.     

Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and 4vHPV vaccine administered according to two- or three-dose schedules in girls aged 9–14 years: Results to month 36 from a randomized trial

This observer-blind study (clinicaltrials.gov NCT01462357) compared the immunogenicity and safety of two doses (2D) of the HPV-16/18 AS04-adjuvanted vaccine (2D of AS04-HPV-16/18) vs. two or three doses of the 4vHPV vaccine [2D or 3D of 4vHPV] in 1075 healthy girls aged 9–14 years. Girls were randomized (1:1:1) to receive 2D of AS04-HPV-16/18 at months (M) 0, 6 (N = 359), 2D of 4vHPV at M0, 6 (N = 358) or 3D of 4vHPV at M0, 2, 6 (N = 358). 351, 339 and 346 girls, respectively, returned for the concluding visit at M36. Superiority was demonstrated at M7 and M12; comparison of the immune response to both vaccine antigens was made between 2D of AS04-HPV-16/18 and 2D or 3D of 4vHPV at subsequent time points in the according-to-protocol immunogenicity cohort (ATP-I; N = 958 at M36) and the total vaccinated cohort (TVC: N = 1036 at M36). HPV-16/18-specific T-cell- and B-cell-mediated immune responses and safety were also investigated. At M36, anti-HPV-16/18 ELISA responses in the 2D AS04-HPV-16/18 group remained superior to those of the 2D and 3D 4vHPV groups. In the M36 TVC, geometric mean titers were 2.78-fold (HPV-16) and 6.84-fold (HPV-18) higher for 2D of AS04-HPV-16/18 vs. 2D of 4vHPV and 2.3-fold (HPV-16) and 4.14-fold (HPV-18) higher vs. 3D of 4vHPV. Results were confirmed by vaccine pseudovirion-based neutralisation assay. Numbers of circulating CD4⁺ T cells and B cells appeared similar across groups. Safety was in line with the known safety profiles of both vaccines. In conclusion, superior HPV-16/18 antibody responses were elicited by 2D of the AS04-HPV-16/18 compared with 2D or 3D of the 4vHPV vaccine in girls aged 9–14 years.Clinical Trial Registration: NCT0146235.     

Efficacy and safety of a quadrivalent influenza vaccine in children aged 6–35 months: A global,multiseasonal, controlled,randomized Phase III study

BackgroundChildren are an important target group for influenza vaccination, but few studies have prospectively evaluated influenza vaccine efficacy (VE) in children under 3 years of age. This was a randomized Phase III trial to assess the efficacy, immunogenicity, and safety of an inactivated quadrivalent influenza vaccine (QIV) in young children (EudraCT: 2016–004904–74).MethodsInfluenza-naïve children aged 6–35 months were randomized during three influenza seasons to receive vaccination with QIV or a non-influenza control vaccine. One group of participants was revaccinated with QIV in the subsequent influenza season. The primary efficacy endpoint was the absolute VE of QIV against influenza caused by any circulating strain. Key secondary efficacy endpoints included the absolute VE of QIV against influenza due to antigenically matching strains and immunogenicity. Safety and reactogenicity were also evaluated.ResultsIn total, 1005 children received QIV and 995 received control vaccine. Influenza A/B infection due to any circulating influenza strain occurred less frequently in children who received QIV versus children receiving a control vaccine. The absolute VE of QIV against any circulating influenza strain was 54% (95% confidence interval [CI]: 37%, 66%). The absolute VE of QIV against antigenically matching influenza strains was 68% (95% CI: 45%, 81%). Mean hemagglutination inhibition titers for all influenza strains in the QIV group increased post-vaccination, whereas increases were minimal in the control vaccine group; results from virus neutralization and neuraminidase-inhibition assays were generally consistent with the hemagglutination inhibition assay findings. Approximately 12 months after primary vaccination with QIV, antibody titers remained higher than pre-vaccination titers for most strains. In participants who were revaccinated, QIV elicited strong antibody responses. The overall safety profile and reactogenicity of QIV was comparable with control vaccine.ConclusionPrimary vaccination with QIV was well tolerated and effective in protecting children aged 6–35 months against influenza.     

Immunogenicity and safety of an adjuvanted inactivated polio vaccine,IPV-Al,following vaccination in children at 2, 4, 6 and at 15–18 months

BackgroundAvailability of affordable inactivated polio vaccines (IPV) is of major importance to meet the increasing global supply needs. The results presented here demonstrate non-inferiority of a reduced-dose, aluminium hydroxide-adjuvanted IPV (IPV-Al) to standard IPV.MethodsA phase 3, observer-blinded, randomised, clinical trial was conducted in Panama in infants who received either IPV-Al (n = 400) or standard IPV (n = 400) at age 2, 4 and 6 months. In the booster trial, subjects received a single dose of IPV-Al at age 15–18 months. The primary endpoint was type-specific seroconversion, defined as an antibody titre ≥4-fold higher than the estimated maternal antibody titre and a titre ≥8, one month after the primary vaccination series. In the booster trial, the primary endpoint was the type-specific booster effects (geometric mean titre (GMT) post-booster (Day 28)/GMT pre-booster (Day 0).ResultsSeroconversion rates following primary vaccination with IPV-Al vs IPV were: 96.1% vs 100% (type 1); 100% vs 100% (type 2); and 99.2% vs 100% (type 3) respectively. IPV-Al was non-inferior to IPV, as the lower 95% confidence limits of the treatment differences were above the pre-defined −10%-point limit: 3.94% (-6.51; −2.01) for type 1; 0.0% (-1.30; −1.37) for type 2; −0.85 (-2.46; 0.40) for type 3. The booster effects for the group primed with IPV-Al versus the group primed with IPV were 25.3 vs 9.2 (type 1), 19.1 vs 6.5 (type 2) and 50.4 vs 12.5 (type 3). IPV-Al had a comparable safety profile to that of IPV.ConclusionsNon-inferiority of IPV-Al to standard IPV with respect to seroconversion after vaccination at 2, 4 and 6 months was confirmed for all three poliovirus serotypes. A robust booster response was demonstrated following vaccination with IPV-Al, regardless of the primary vaccine received. Both vaccines were well tolerated.ClinicalTrials.gov identifiers: NCT03025750 and NCT03671616.Funding: Bill & Melinda Gates Foundation.     

Active-controlled phase III study of an egg-cultivated quadrivalent inactivated split-virion influenza vaccine (GC3110A) in healthy Korean children aged 6–35 months

The inactivated trivalent influenza vaccine (TIV) offers limited protection when two influenza B lineages co-circulate or when there is a vaccine mismatch (i.e., discordance in the predominant circulating B strain and WHO-recommended B strain). Inactivated quadrivalent influenza vaccine (QIV) may reduce the burden of influenza. Here, we report the results of a phase 3 clinical trial that evaluated the immunogenicity and safety of a novel QIV, GC3110A, in Korean children aged 6–35 months, which has been approved and is currently in use in Korea. The study involved two parts. In Part 1, the safety of GC3110A was evaluated in 10 subjects. After none of the subjects reported grade 3 adverse events (AEs), we proceeded to Part 2. Part 2 was a randomized, double-blind, multicenter phase 3 trial wherein we compared the immunogenicity and safety of GC3110A with those of a licensed control TIV. Immunogenicity was evaluated by measuring hemagglutination inhibition titers. The 200 participants enrolled in Part 2 were randomized in a 4:1 ratio to receive GC3110A or control TIV. The study vaccine group met both primary (i.e., the lower limit of 95% confidence interval [CI] of the seroconversion rate exceeds 40% for four strains) and secondary (i.e., the lower limit of 95% CI of the seroprotection rate exceeds 70% for four strains) immunogenicity endpoints. There was no significant between-group difference in the seroconversion rate, seroprotection rate, and geometric mean titer for the shared strains. However, the study vaccine group demonstrated significantly higher immunity for the additional strain B/Yamagata. In the safety analysis, there was no significant between-group difference in the proportion of participants with solicited local AEs, solicited systemic AEs, and unsolicited AEs. In conclusion, the results indicate that GC3110A has comparable immunogenicity and safety to those of TIV.Clinical Trial Registry Number: NCT03285997.     

Phase III: Randomized observer-blind trial to evaluate lot-to-lot consistency of a new plant-derived quadrivalent virus like particle influenza vaccine in adults 18–49 years of age

BackgroundThe global reliance on eggs to produce most influenza vaccines has several limitations and new approaches to influenza vaccine production are needed. Herein we describe a phase 3, lot-to-lot consistency trial (NCT03321968) of a quadrivalent, recombinant, virus-like particle (VLP) influenza vaccine produced in plants. This platform is based on transient expression of proteins in Nicotiana benthamiana and yields VLPs bearing hemagglutinin (HA) protein trimers that are combined in a quadrivalent vaccine (QVLP).MethodsThe HAs targeted in this study were A/California/07/2009 H1N1, A/Hong Kong/4801/2014 H3N2, B/Brisbane/60/08 and B/Phuket/3073/2013: recommended for the 2016–2017 Northern Hemisphere season. Healthy adults 18–49 years of age (n = 1200) were randomized 1:1:1 to receive a 0.5 mL intramuscular injection of QVLP (30 μg HA/strain) from three sequential lots. Local and systemic reactions were monitored for 21 days post-vaccination and blood was collected pre-vaccination and at day 21 (D21) after vaccination to measure hemagglutination inhibition (HI) antibodies.ResultsSubject demographics were similar between groups and compliance with study procedures was 96.3%. The study population was 54.8% female, the mean age (±SD) was 29.9 ± 9.01 and the racial distribution was 77.8% Caucasian, 15.6% Asian, 5.8% Black/African American and 0.8% other. The HI responses met the Center for Biologics Evaluation and Research criteria for seroconversion (SCR ≥ 40%) and seroprotection rates (SPR ≥ 70%). The geometric mean fold rise in HI titers was ≥ 2.5 for all 4 strains for each lot. Lot-to-lot consistency was met with the 95% confidence intervals of the D21 mean geometric titre ratios falling between 0.67 and 1.5 for all four strains. No safety concerns were identified. Solicited adverse events were generally mild and transient: typical for what is reported after inactivated influenza vaccines.ConclusionsThis study supported earlier findings of the safety profile and immunogenicity of the plant-derived QVLP and demonstrated the consistency with which it can be produced.     

Impact of kangaroo care after caesarean section on paternal–infant attachment and involvement at 12 months: A longitudinal study in Turkey

The mother's first meeting with the baby after the caesarean section is usually delayed due to the reasons arising from the mother and the baby in Turkey. Although there are many benefits of kangaroo care (KC) intervention between the mother and the newborn, there is a limited number of studies on the KC intervention between the newborn and the father after caesarean section in international literature, and there are none in Turkey. This study was carried out to determine the effect of fathers and infants who participated in KC, immediately after birth by caesarean section, on paternal–infant attachment and the fathers' involvement in infant care in the 12th month. The study was conducted as a longitudinal study with a control group. Initially, the sample consisted of 60 fathers. However, the study was completed with 48 fathers. KC intervention was practised to the couple of the father and the infant in the experimental group, while no practice was given to the control group. Fathers in the experimental group were told that they should continue to practice KC intervention at least two times a week until their baby will be 1-year-old. The data collection forms were given to fathers face-to-face in the first interview, and then through phone calls and emails after 12 months. The status of the fathers in the experimental group fathers' involvement in infant care of the baby (p = .005) was significantly higher than the control group. The mean score for the Postnatal Paternal-Infant Attachment Questionnaire (PPAQ), in fathers who participated in KC intervention, was higher than that of fathers who did not participate in the KC intervention (p < .005). The results of this study demonstrated that the paternal–infant attachment and the fathers' participation in infant care were more positive in fathers and babies who performed the KC intervention.     

Estimated influenza illnesses and hospitalizations averted by influenza vaccination among children aged 6–59 months in Suzhou,China, 2011/12 to 2015/16 influenza seasons

BackgroundThere are few estimates of vaccination-averted influenza-associated illnesses in China.MethodsWe used a mathematical model and Monte Carlo algorithm to estimate numbers and 95% confidence intervals (CI) of influenza-associated outcomes (hospitalization, illness, and medically-attended (MA) illness) averted by vaccination among children aged 6–59 months in Suzhou from October 2011–September 2016. Influenza illnesses included non-hospitalized MA influenza illnesses and non-MA influenza illnesses. The numbers of influenza-associated outcomes averted by vaccination were the difference between the expected burden if there were no vaccination given and the observed burden with vaccination. The model incorporated the disease burden estimated based on surveillance data from Suzhou University Affiliated Children’s Hospital (SCH) and data from health utilization surveys conducted in the catchment area of SCH, age-specific estimates of influenza vaccination coverage in Suzhou from the Expanded Program on Immunization database, and influenza vaccine effectiveness estimates from previous publications. Averted influenza estimations were presented as absolute numbers and in terms of the prevented fraction (PF). A hypothetical scenario with 50% coverage (but identical vaccine effectiveness) over the study period was also modeled.ResultsIn ~250,000 children, influenza vaccination prevented an estimated 731 (CI: 549–960) influenza hospitalizations (PF: 6.2% of expected, CI: 5.8–6.6%) and 10,024 (7593–12,937) influenza illnesses (PF: 6.5%, 6.4–6.7%), of which 8342 (6338–10,768) were MA (PF: 6.6%, 6.4–6.7%) from 2011 to 2016. The PFs declined each year along with decreasing influenza vaccination coverage. If 50% of the study population had been vaccinated over time, the estimated numbers of averted cases during the study period would have been 4059 (3120–5762) influenza hospitalizations (PF: 27.2%, 26.4–27.9%) and 56,215 (42,925–78,849) influenza illnesses (PF: 28.5%, 28.3–28.7%), of which 46,596 (35,662–65,234) would be MA (PF: 28.5%, 28.3–28.7%).ConclusionInfluenza vaccination is estimated to have averted influenza-associated illness outcomes even with low coverage in children aged 6–59 months in Suzhou. Increasing influenza vaccination coverage in this population could further reduce illnesses and hospitalizations.     

Transiently increased IgE responses in infants and pre-schoolers receiving only acellular Diphtheria–Pertussis–Tetanus (DTaP) vaccines compared to those initially receiving at least one dose of cellular vaccine (DTwP) – Immunological curiosity or canary in the mine?

BackgroundSeveral previous studies have highlighted the strong Th2-polarising and IgE-promoting activity of the DTaP vaccine, but there is no evidence that this has pathological consequences and accordingly there is no current interest amongst vaccine developers in reformulating DTaP to attenuate these properties. In light of an apparent resurgence in pertussis in many countries, and emerging evidence from other areas of paediatric immunology of IgE-mediated interference with host defence mechanisms, this issue requires more detailed clarification.MethodsWe have re-evaluated the impact of DTaP-only versus mixed DTwP/DTaP vaccination on Th2-dependent “bystander” IgE responses in three cohorts of children under different priming conditions, encompassing both vaccine-targeted and unrelated antigens including food allergens.ResultsWe confirm the generalised IgE-trophic activity of the DTaP vaccine in pre-schoolers and demonstrate similar (albeit transient) effects in infants. We additionally demonstrate that use of an alternative mixed infant priming schedule encompassing an initial dose of DTwP significantly attenuates this property.InterpretationCentral to our interpretation of these findings are studies demonstrating: (i) mixed DTwP/DTaP priming improves resistance to pertussis disease and attenuates the IgE-stimulatory component of long term vaccine-specific memory; (ii) IgE-mediated mechanisms can interfere with innate antiviral immunity and accordingly exacerbate airway symptoms in infected children. These observations, taken together with the data presented here, suggest a plausible mechanistic link between baseline pertussis-specific IgE titres in DTaP vaccinees and susceptibility to pertussis disease, which merits testing. Retrospective IgE analyses on sera collected from children at the time of presentation with pertussis could resolve this issue.     

Two consecutive randomized controlled pertussis booster trials in children initially vaccinated in infancy with an acellular vaccine: The first with a five-component Tdap vaccine to 5-year olds and the second with five- or monocomponent Tdap vaccines at age 14–15 years

Prior study children from a DTaP efficacy trial were recruited at ages 5 and 15 years to randomized booster trials addressing immunogenicity and reactogenicity; 475 preschool children received mixed or separate injections of a reduced antigen vaccine (Tdap5, Sanofi Pasteur MSD) and an inactivated polio vaccine, and 230 adolescents received the same or another booster vaccine (Tdap1, SSI, Denmark).Pre-vaccination antibody concentrations against pertussis antigens were significantly higher at 15 than 5 years of age, probably due to natural boosting between the studies. Tdap5 induced comparable anti-PT concentrations at both ages, but antibody responses were significantly higher to filamentous haemagglutinin, pertactin and fimbriae 2/3 in adolescents. As expected, a higher amount of PT (Tdap1, 20 μg) induced a stronger anti-PT response than a lower amount (Tdap5, 2.5 μg).The frequency of adverse events was low and there were no serious adverse reactions. All local reactions had an early onset and a short duration. A large swelling or redness of more than half of the upper arm circumference was reported in 8/475 5-year-olds and in 6/230 15-year-olds. Children vaccinated with Tdap5 reported more moderate pain in adolescence than at preschool age, whereas itching was only reported in preschool children.Sweden introduced DTaP vaccines in 1996 after a 17-year hiatus with no general pertussis vaccination and pertussis was still endemic at the time of the studies. The frequency of adverse events was nevertheless low in both preschool children and adolescents and antibody responses were adequate. These studies document immunogenicity and reactogenicity in a trial cohort consecutively vaccinated with acellular pertussis vaccines from infancy to adolescence.The adolescent study was registered at ClinicalTrials.gov on 26 March 2009 (NCT00870350).     

Antibody persistence at 18-20 months of age and safety and immunogenicity of a booster dose of a combined DTaP-IPV//PRP∼T vaccine compared to separate vaccines (DTaP, PRP∼T and IPV) following primary vaccination of healthy infants in the People's Republic of China

This study assessed the antibody persistence, and the immunogenicity and safety of a booster dose of a DTaP-IPV//PRP∼T (Pentaxim^®, Sanofi Pasteur's AcXim family) combined vaccine and of standalone vaccines one year after primary vaccination in the People's Republic of China. Participants (N = 719) previously primed with DTaP-IPV//PRP∼T at 2, 3, 4 months (Group A, N = 255), 3, 4, 5 months (Group B, N = 233), or DTaP (Wuhan Institute of Biological Products), PRP-T (Act-Hib^®) and IPV (Imovax^® Polio) at 3, 4, 5 months (Group C, N = 231) received boosters of the same vaccines at 18-20 months of age. Seroprotection (SP) and seroconversion (SC) were determined before and 1 month after the booster. Safety was monitored from parental reports. In all groups 87.6-100% of participants had pre-booster protective anti-PRP, -diphtheria, -tetanus and -poliovirus antibody titers; post-booster, all SP rates were 100% and SC was ≥80.4% for anti-pertussis titers ≥ 4-fold increase. Reactogenicity was low for each group. These data support the use of the DTaP-IPV//PRP∼T vaccine in the People's Republic of China compared to separate DTaP, IPV, and PRP∼T administration in terms of both safety and immunogenicity.     

Immunogenicity and safety of two novel human papillomavirus 4- and 9-valent vaccines in Chinese women aged 20–45 years: A randomized,blinded, controlled with Gardasil (type 6/11/16/18), phase III non-inferiority clinical trial

BackgroundHuman papillomavirus (HPV) infections were the main cause of anogenital cancers and warts. HPV 6/11/16/18 vaccines provide protection against the high-risk types of HPV responsible for 70% of cervical cancers and 90% of genital warts. This randomized, blinded, non-inferiority phase III trial was to determine whether immunogenicity and tolerability would be non-inferior among women after receiving two novel 4- and 9-valent HPV vaccines (4vHPV, HPV 6/11/16/18; 9vHPV, HPV 6/11/16/18/31/33/45/52/58) compared with those receiving Gardasil 4 (4-valent).Methods1680 females between 20 and 45 years were randomized in a 2:1:1 ratio to 20–26, 27–35, or 36–45 y groups. Subjects then equally assigned to receive 4vHPV, 9vHPV or Gardasil 4 (control) vaccine at months 0, 2, and 6. End points included non-inferiority of HPV-6/11/16/18 antibodies for 4vHPV versus control, and 9vHPV versus control and safety. The immunogenicity non-inferiority was pre-defined as the lower bound of 95% confidence interval (CI) of seroconversion rate (SCR) difference > ?10% and the lower bound of 95% CI of geometric mean antibody titer (GMT) ratio > 0.5.ResultsAmong the three vaccine groups, more than 99% of the participants seroconverted to all 4 HPV types. The pre-specified statistical non-inferiority criterion for the immunogenicity hypothesis was met: all the lower bounds of 95% CIs on SCR differences exceeded ?10% for each vaccine HPV type and the corresponding lower bounds of 95% CIs for GMT ratios > 0.5. Across vaccination groups, the most common vaccination reaction were injection-site adverse events (AEs), including pain, swelling, and redness. General and serious AEs were similar in the three groups. There were no deaths.ConclusionsThis study demonstrated that the novel 4- and 9-valent HPV vaccination was highly immunogenic and generally well tolerated, both of which were non-inferior to Gardasil 4 in immunogenicity and safety.