Human infections with the avian influenza A(H7N9) virus were first reported in China in 2013 and continued to occur in annual waves. In the 2016/2017 fifth wave, Yangtze River Delta (YRD) lineage ...viruses, which differed antigenically from those of earlier waves, predominated.
In this phase 2 double-blinded trial we randomized 720 adults ≥ 19 years of age to receive two injections of a YRD lineage inactivated A/Hong Kong/125/2017 fifth-wave H7N9 vaccine, given 21 days apart, at doses of 3.75, 7.5, and 15 µg of hemagglutinin (HA) with AS03A adjuvant and at doses of 15 and 45 µg of HA without adjuvant.
Two doses of adjuvanted vaccine were required to induce HA inhibition (HI) antibody titers ≥ 40 in most participants. After two doses of the 15 µg H7N9 formulation, given with or without AS03 adjuvant, the proportion achieving a HI titer ≥ 40 against the vaccine strain at 21 days after the second vaccination was 65 % (95 % CI, 57 %-73 %) and 0 % (95 % CI, 0 %-4%), respectively. Among those who received two doses of the 15 µg adjuvanted formulation the proportion with HI titer ≥ 40 at 21 days after the second vaccination was 76 % (95 % CI, 66 %-84 %) in those 19–64 years of age and 49 % (95 % CI, 37 %-62 %) in those ≥ 65 years of age. Responses to the adjuvanted vaccine formulations did not vary by HA content. Antibody responses declined over time and responses against drifted H7N9 strains were diminished. Overall, the vaccines were well tolerated but, as expected, adjuvanted vaccines were associated with more frequent solicited systemic and local adverse events.
AS03 adjuvant improved the immune responses to an inactivated fifth–wave H7N9 influenza vaccine, particularly in younger adults, but invoked lower responses to drifted H7N9 strains. These findings may inform future influenza pandemic preparedness strategies.
Abstract
Background
We evaluated the associations between baseline influenza virus–specific hemagglutination inhibition (HAI) and microneutralization (MN) titers and subsequent symptomatic influenza ...virus infection in a controlled human infection study.
Methods
We inoculated unvaccinated healthy adults aged 18–49 years with an influenza A/California/04/2009/H1N1pdm-like virus (NCT04044352). We collected serial safety labs, serum for HAI and MN, and nasopharyngeal swabs for reverse-transcription polymerase chain reaction (RT-PCR) testing. Analyses used the putative seroprotective titer of ≥40 for HAI and MN. The primary clinical outcome was mild-to-moderate influenza disease (MMID), defined as ≥1 postchallenge positive qualitative RT-PCR test with a qualifying symptom/clinical finding.
Results
Of 76 participants given influenza virus challenge, 54 (71.1%) experienced MMID. Clinical illness was generally very mild. MMID attack rates among participants with baseline titers ≥40 by HAI and MN were 64.9% and 67.9%, respectively, while MMID attack rates among participants with baseline titers <40 by HAI and MN were 76.9% and 78.3%, respectively. The estimated odds of developing MMID decreased by 19% (odds ratio, 0.81 95% confidence interval, .62–1.06; P = .126) for every 2-fold increase in baseline HAI. There were no significant adverse events.
Conclusions
We achieved a 71.1% attack rate of MMID. High baseline HAI and MN were associated with protection from illness.
Clinical Trials Registration. NCT04044352.
In a multicenter controlled human infection model study, we inoculated 76 participants with influenza A/California/04/2009/H1N1pdm-like virus and safely achieved a 71.1% attack rate of mild-to-moderate influenza disease. High virus-specific hemagglutination inhibition and microneutralization titers were associated with protection from illness.
Abstract Purpose To improve adolescent immunization coverage in a rural North Carolina county. Methods Adolescent immunization coverage rates in an intervention and four comparison counties were ...compared over 1 year. We introduced practice-based interventions in seven practices centering on immunization registry-driven recall of adolescents for immunizations with postcard reminders (Phase 1), and 6 months later employed nontargeted school-generated telephone reminders to parents of adolescents (Phase 2). Results Improvements in the intervention county among 11- to 12-year-olds occurred for first-dose human papillomavirus vaccine in both boys (overall change, 14.2%–32.1%) and girls (27.4%–43.4%) and the meningococcal vaccine (34.6%–49.4%). Improvements among adolescents 13–18 years were limited to human papillomavirus vaccine completion in boys (1.6%–4.2%). Improvements were greater during Phase 1 than Phase 2 and among younger adolescents. Coverage improvements in the comparison counties were smaller than those observed in the intervention county. Conclusions A resource-light two-phase intervention led to modest improvements in immunization coverage, most notably in the largest adolescent practice in the county, and suggested potential for further gains, particularly among younger adolescents.
Adjuvanted inactivated influenza vaccine (aIIV) and high-dose inactivated influenza vaccine (HD-IIV) are U.S.-licensed for adults aged ≥ 65 years. This study compared serum hemagglutination ...inhibition (HAI) antibody titers for the A(H3N2) and A(H1N1)pdm09 and B strains after trivalent aIIV3 and trivalent HD-IIV3 in an older adult population.
The immunogenicity population included 342 participants who received aIIV3 and 338 participants who received HD-IIV3. The proportion of participants that seroconverted to A(H3N2) vaccine strains after allV3 (112 participants 32.8%) was inferior to the proportion of participants that seroconverted after HD-IIV3 (130 participants 38.5%) at day 29 after vaccination (difference, - 5.8%; 95%CI, - 12.9% to 1.4%). There were no significant differences between the vaccine groups in percent seroconversion to A(H1N1)pdm09 or B vaccine strains, in percent seropositivity for any of the strains, or in post-vaccination GMT for the A(H1N1)pdm09 strain. The GMTs for the post-vaccination A(H3N2) and B strains were higher after HD-IIV than after aIIV3.
Overall immune responses were similar after aIIV3 and HD-IIV3. For the primary outcome, the aIIV3 seroconversion rate for H3N2 did not meet noninferiority criteria compared with HD-IIV3, but the HD-IIV3 seroconversion rate was not statistically superior to the aIIV3 seroconversion rate.
ClinicalTrials.gov Identifier: NCT03183908.
Understanding the relationship between human papillomavirus (HPV) knowledge and vaccination behavior is important to inform public health interventions, yet few validated HPV knowledge scales exist. ...This study describes development of the
(HPV-KQ) and its validation with parents residing in the southern United States (US).
Drawing on previously published measures, we developed the 13-item HPV-KQ and administered the scale via Web-based survey to parents (N=1105) of adolescents ages 9 to 17 years. Dimensionality, internal consistency, model fit, and predictive validity were assessed.
The scale was bidimensional. One factor captured general HPV knowledge, and the second factor captured perceptions of gender differences in HPV infection and vaccine recommendations. The 13-item scale and 2-factor solution displayed strong internal consistency and good model fit. Parents of vaccinated adolescents scored higher on the 13-item HPV-KQ (Mean = 8.56) than parents of unvaccinated adolescents (Mean = 6.43) (p < .001). In regression models, controlling for key covariates, parents' performance on the HPV-KQ predicted adolescent HPV vaccination (p < .001).
Evaluation indicates the HPV-KQ is a reliable and valid tool for measuring knowledge of HPV and the HPV vaccine among parents residing in the southern US. We recommend further efforts to validate the scale with other populations.
This report updates the 2016–17 recommendations of the Advisory Committee on Immunization Practices (ACIP) regarding the use of seasonal influenza vaccines (MMWR Recomm Rep 2016;65No. RR-5). Routine ...annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications. A licensed, recommended, and age-appropriate vaccine should be used.
For the 2017–18 season, quadrivalent and trivalent influenza vaccines will be available. Inactivated influenza vaccines (IIVs) will be available in trivalent (IIV3) and quadrivalent (IIV4) formulations. Recombinant influenza vaccine (RIV) will be available in trivalent (RIV3) and quadrivalent (RIV4) formulations. Live attenuated influenza vaccine (LAIV4) is not recommended for use during the 2017–18 season due to concerns about its effectiveness against (H1N1)pdm09 viruses during the 2013–14 and 2015–16 seasons. Recommendations for different vaccine types and specific populations are discussed. No preferential recommendation is made for one influenza vaccine product over another for persons for whom more than one licensed, recommended product is available.
Updates to the recommendations described in this report reflect discussions during public meetings of ACIP held on October 20, 2016; February 22, 2017; and June 21, 2017. New and updated information in this report includes the following:
• Vaccine viruses included in the 2017–18 U.S. trivalent influenza vaccines will be an A/Michigan/45/2015 (H1N1) pdm09–like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008–like virus (Victoria lineage). Quadrivalent influenza vaccines will contain these three viruses and an additional influenza B vaccine virus, a B/Phuket/3073/2013–like virus (Yamagata lineage).
• Information on recent licensures and labelling changes is discussed, including licensure of Afluria Quadrivalent (IIV4; Seqirus, Parkville, Victoria, Australia); Flublok Quadrivalent (RIV4; Protein Sciences, Meriden, Connecticut); and expansion of the age indication for FluLaval Quadrivalent (IIV4; ID Biomedical Corporation of Quebec, Quebec City, Quebec, Canada), previously licensed for ≥3 years, to ≥6 months.
• Pregnant women may receive any licensed, recommended, age-appropriate influenza vaccine.
• Afluria (IIV3; Seqirus, Parkville, Victoria, Australia) may be used for persons aged ≥5 years, consistent with Food and Drug Administration–approved labeling.
• FluMist Quadrivalent (LAIV4; MedImmune, Gaithersburg, Maryland) should not be used during the 2017–18 season due to concerns about its effectiveness against influenza A(H1N1)pdm09 viruses in the United States during the 2013–14 and 2015–16 influenza seasons.
This report focuses on the recommendations for use of vaccines for the prevention and control of influenza during the 2017–18 season in the United States. A Background Document containing further information and a summary of these recommendations are available at https://www.cdc.gov/vaccines/hcp/acip-recs/vacc-specific/flu.html. These recommendations apply to licensed influenza vaccines used within Food and Drug Administration–licensed indications, including those licensed after the publication date of this report. Updates and other information are available at CDC’s influenza website (https://www.cdc.gov/flu). Vaccination and health care providers should check CDC’s influenza website periodically for additional information.
Administering inactivated influenza vaccine (IIV), 13-valent pneumococcal conjugate vaccine (PCV13), and diphtheria-tetanus-acellular pertussis (DTaP) vaccine together has been associated with ...increased risk for febrile seizure after vaccination. We assessed the effect of administering IIV at a separate visit from PCV13 and DTaP on postvaccination fever.
In 2017-2018, children aged 12 to 16 months were randomly assigned to receive study vaccines simultaneously or sequentially. They had 2 study visits 2 weeks apart; nonstudy vaccines were permitted at visit 1. The simultaneous group received PCV13, DTaP, and quadrivalent IIV (IIV4) at visit 1 and no vaccines at visit 2. The sequential group received PCV13 and DTaP at visit 1 and IIV4 at visit 2. Participants were monitored for fever (≥38°C) and antipyretic use during the 8 days after visits.
There were 110 children randomly assigned to the simultaneous group and 111 children to the sequential group; 90% received ≥1 nonstudy vaccine at visit 1. Similar proportions of children experienced fever on days 1 to 2 after visits 1 and 2 combined (simultaneous 8.1% versus sequential 9.3%; adjusted relative risk = 0.87 95% confidence interval 0.36-2.10). During days 1 to 2 after visit 1, more children in the simultaneous group received antipyretics (37.4% vs 22.4%;
= .020).
In our study, delaying IIV4 administration by 2 weeks in children receiving DTaP and PCV13 did not reduce fever occurrence after vaccination. Reevaluating this strategy to prevent fever using an IIV4 with a different composition in a future influenza season may be considered.
The quadrivalent HPV vaccine (4vHPV) was originally recommended as a three-dose series (0/2/6 months), though delays in completing the series frequently occur. We previously found delayed dosing in ...girls resulted in similar or higher antibody titers compared to on-time dosing. Archived sera from 262 healthy females aged 9-18 recruited from pediatric clinics were tested to determine if delayed dosing intervals affected antibody avidity. Avidity index (AI; ratio of IgG Ab bound in the treated and untreated sample) was determined pre- and post-dose 3 4vHPV for each participant using a modified multiplex ELISA. Data were grouped by dosing intervals: (1) on-time dose 2 and 3, (2) delayed dose 2 and on-time dose 3, (3) on-time dose 2 and delayed dose 3, (4) delayed dose 2 and 3. Overall, mean AI was highest for HPV16 and lowest for HPV6. As expected, AI did not differ between groups 1 & 3 or groups 2 & 4 pre-dose 3, however, for most types mean AI was significantly higher both pre- and post-dose 3 for groups with delayed dose 2. For all types, mean AI was higher post-dose 3 in all delayed dosing groups compared to group 1. One month post-dose 3, there was a positive but weak correlation between AIs and antibody titer for HPV 6 (ρ = 0.25, p = .0001), HPV 11 (ρ = 0.14, p = .0370), HPV 16 (ρ = 0.11, p = .0934), and HPV 18 (ρ = 0.37, p < .0001). Our findings suggest longer intervals between doses result in higher antibody avidity, providing further evidence that delayed dosing of 4vHPV does not hinder the immune response.
Despite the absence of adequate safety or efficacy data, clindamycin is widely prescribed in the neonatal intensive care unit. We evaluated the association between clindamycin exposure and adverse ...events, as well as antibiotic effectiveness in infants.
This was a retrospective cohort study of infants receiving clindamycin before postnatal day 121 who were discharged from a Pediatrix Medical Group neonatal intensive care unit (1997-2015). Using a previously developed pharmacokinetic model, we performed simulations to predict clindamycin exposure based on available dosing data. We used multivariable logistic regression to evaluate the association between clindamycin exposure and safety outcomes during and after clindamycin therapy. We reported the proportion of infants with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and clearance of MRSA bacteremia.
A total of 4089 infants received clindamycin at a median (25th-75th percentile) dose of 15 mg/kg/d (12-16). Clearance increased with older gestational age. Infants with the highest total clindamycin exposure had marginally increased odds of necrotizing enterocolitis within 7 days (adjusted odds ratio = 1.95 1.04-3.63), but exposure was not associated with death, sepsis, seizures, intestinal perforation or intestinal strictures. Of 25 infants who had MRSA bacteremia, 19 (76%) cleared the infection by the end of the clindamycin course.
Higher clindamycin exposure was not associated with increased odds of death or nonlaboratory adverse events. The use of pharmacokinetic models combined with available electronic health record data offers a valuable, cost-effective approach to analyzing the safety and effectiveness of drugs in infants when large-scale trials are not feasible.
PDF
