Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-8 (of 8 Records) |
Query Trace: Alcorn L[original query] |
---|
A randomized controlled trial of antibody response to 2019-20 cell-based inactivated and egg-based live attenuated influenza vaccines in children and young adults (preprint)
Williams KV , Zhai B , Alcorn JF , Patricia Nowalk M , Levine MZ , Kim SS , Flannery B , Moehling Geffel K , Jaber Merranko A , Nagg JP , Collins M , Susick M , Clarke KS , Zimmerman RK , Martin JM . medRxiv 2021 2021.09.02.21263043 Background Hemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children and young adult HAI titers against the 2019-2020 LAIV4 and ccIIV4.Methods Participants aged 4-21 years were randomized 1:1 to receive ccIIV4 (n =100) or LAIV4 (n=98). Blood was drawn prevaccination and on day 28 (21-35) post vaccination. HAI assays against egg-grown A/H1N1, A/H3N2, both vaccine B strains and cell-grown A/H3N2 antigens were conducted. Outcomes were geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers.Results GMTs to A/H1N1, A/H3N2 and B/Victoria increased following both ccIIV and LAIV and to B/Yamagata following ccIIV (p<0.05). The GMFR range was 2.4-3.0 times higher for ccIIV4 than for LAIV4 (p<0.001). Within vaccine types, egg-grown A/H3N2 GMTs were higher (p<0.05) than cell-grown GMTs [ccIIV4 day 28: egg=205 (95% CI: 178-237); cell=136 (95% CI:113-165); LAIV4 day 28: egg=96 (95% CI: 83-112); cell=63 (95% CI: 58-74)]. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar. Pre-vaccination titers inversely predicted GMFR.Conclusion The HAI response to ccIIV4 was greater than LAIV4 in this study of mostly older children, and day 0 HAI titers inversely predicted GMFR for both vaccines. For both vaccines, the A/H3N2 cell-grown antigen levels were lower than egg-grown, but the GMFR for cell-grown and egg-grown did not differ significantly within vaccine type.Clinical Trials No NCT03982069Competing Interest StatementConflict of Interest: RKZ has received funding by Sanofi for an unrelated study. MPN has research funding from Merck & Co., Inc. for an unrelated study. JMM has received funding from Merck, Sharp and Dohme for an unrelated study.Clinical TrialClinical Trials No.: NCT03982069Funding StatementThis work was supported by the Centers for Disease Control and Prevention (CDC) [5U01IP001035] and by National Institutes of Health (NIH) [UL1TR001857], [KL2 TR001856], and/or [TL1 TR001858]. This work represents the views of the authors and not the CDC or NIH. Pennsylvania Statewide Immunization Information System (PA-SIIS) vaccine registry was used to verify vaccination status. These data were supplied in part by the Bureau of Health Statistics & Registries, Pennsylvania Department of Health, Harrisburg, Pennsylvania. The Pennsylvania Department of Health specifically disclaims responsibility for any analyses, interpretations, or conclusions. REDCap and the Department of Biomedical Informatics grant support (Clinical and Translational Sciences Institute at the University of Pittsburgh Grant Number UL1-TR-001857). Study data were collected and managed using REDCap electronic data capture tools hosted at the University of Pittsburgh. Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The Institutional Review Boards at the University of Pittsburgh and the Centers for Disease Control and Prevention (CDC) approved this study. Written informed consent and assent, where appropriate, were obtained from all participants and/or their parents/legal guardians prior to beginning study procedures.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field expla ning why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData can be made available upon request.HAIhemagglutination inhibition assayIIVinactivated influenza vaccineccIIV4cell-culture-based inactivated influenza vaccine quadrivalentLAIV4Egg-based live attenuated influenza vaccine quadrivalentEMRElectronic medical recordRDEReceptor-destroying enzymePBSPhosphate-buffered salineCDCCenters for Disease Control and PreventionFDAFood and Drug AdministrationGMTGeometric mean titersGMFRGeometric mean fold riseACIPAdvisory Committee on Immunization PracticePA-SIISPennsylvania Statewide Immunization Information System |
A randomized controlled trial to compare immunogenicity to cell-based versus live-attenuated influenza vaccines in children
Williams KV , Li ZN , Zhai B , Alcorn JF , Nowalk MP , Levine MZ , Kim SS , Flannery B , Moehling Geffel K , Merranko AJ , Collins M , Susick M , Clarke KS , Zimmerman RK , Martin JM . J Pediatric Infect Dis Soc 2023 12 (6) 342-352 BACKGROUND: Few studies have focused on the immune response to more recent influenza vaccine formulations such as cell-cultured inactivated influenza vaccine (ccIIV4) or live-attenuated influenza vaccine (LAIV4) in older children and young adults, or differences in immunoglobulin response using newer antibody landscape technology. METHODS: Participants ages 4-21 were randomized to receive ccIIV4 (n = 112) or LAIV4 (n = 118). A novel high-throughput multiplex influenza antibody detection assay was used to provide detailed IgG, IgA, and IgM antibody isotypes, along with hemagglutination inhibition levels (HAI), measured pre- and 28 days post-vaccination. RESULTS: The HAI and immunoglobulin isotype response to ccIIV4 was greater than LAIV4, with significant increases in IgG but not IgA or IgM. The youngest participants had the highest LAIV4 response. Prior LAIV4 vaccination was associated with a higher response to current season ccIIV4. Cross-reactive A/Delaware/55/2019(H1N1)pdm09 antibodies were present pre-vaccination and increased in response to ccIIV4, but not LAIV4. Immunoglobulin assays strongly correlated with and confirmed the findings of HAI titers to measure immune response. CONCLUSIONS: Age and prior season vaccination may play a role in the immune response in children and young adults to ccIIV4 and LAIV4. While immunoglobulin isotypes provide high-level antigen-specific information, HAI titers alone can provide a meaningful representation of day 28 post-vaccination response. CLINICAL TRIALS NO: NCT03982069. |
Factors associated with humoral immune response in older adults who received egg-free influenza vaccine
Williams KV , Moehling Geffel K , Alcorn JF , Patricia Nowalk M , Levine MZ , Kim SS , Flannery B , Susick M , Zimmerman RK . Vaccine 2022 41 (3) 862-869 BACKGROUND: Immune responses to influenza vaccination tend to be lower among older, frequently vaccinated adults. Use of egg-free influenza vaccines is increasing, but limited data exist on factors associated with their immunogenicity in older adults. METHODS: Community-dwelling older adults ≥ 56 years of age were enrolled in a prospective, observational study of immunogenicity of 2018-2019 influenza vaccine. Hemagglutination inhibition (HAI) antibody titers were measured pre-vaccination (Day 0) and four weeks after vaccination (Day 28) to calculate geometric mean titers, seropositivity (HAI titers ≥ 1:40), seroconversion (fourfold rise in HAI titer with post-vaccination titer ≥ 1:40) and geometric mean fold rise (GMFR). Linear regression models assessed the association of predictors of GMFR for each vaccine antigen. RESULTS: Among 91 participants who received egg-free influenza vaccines, 84 (92.3 %) received quadrivalent recombinant influenza vaccine (RIV4, Flublok, Sanofi Pasteur), and 7 (7.7 %) received quadrivalent cell culture-based influenza vaccine (ccIIV4, Flucelvax, Seqirus). Pre-vaccination seropositivity was 52.8 % for A(H1N1), 94.5 % for A(H3N2), 61.5 % for B/Colorado and 48.4 % for B/Phuket. Seroconversion by antigen ranged from 16.5 % for A(H1N1) and B/Colorado to 37.4 % for A(H3N2); 40 participants failed to seroconvert to any antigen. Factors independently associated with higher GMFR in multivariable models included lower pre-vaccination HAI antibody titer for A(H1N1), B/Colorado and B/Phuket, and younger age for A(H1N1). CONCLUSION: Overall pre-vaccination seropositivity was high and just over half of the cohort seroconverted to ≥ 1 vaccine antigen. Antibody responses were highest among participants with lower pre-vaccination titers. Among older adults with high pre-existing antibody titers, approaches to improve immune responses are needed. |
A randomized controlled trial of antibody response to 2019-20 cell-based inactivated and egg-based live attenuated influenza vaccines in children and young adults
Williams KV , Zhai B , Alcorn JF , Patricia Nowalk M , Levine MZ , Kim SS , Flannery B , Moehling Geffel K , Jaber Merranko A , Nagg JP , Collins M , Susick M , Clarke KS , Zimmerman RK , Martin JM . Vaccine 2021 40 (5) 780-788 BACKGROUND: Hemagglutination inhibition (HAI) titers to the live-attenuated influenza vaccine (LAIV4) are typically lower than its counterpart egg-based inactivated influenza vaccines (IIV). Similar comparisons have not been made between LAIV4 and the 4-strain, cell-culture inactivated influenza vaccine (ccIIV4). We compared healthy children's and young adults' HAI titers against the 2019-2020 LAIV4 and ccIIV4. METHODS: Participants aged 4-21 years were randomized 1:1 to receive ccIIV4 (n = 100) or LAIV4 (n = 98). Blood was drawn prevaccination and on day 28 (21-35) post vaccination. HAI assays against egg-grown A/H1N1, A/H3N2, both vaccine B strains and cell-grown A/H3N2 antigens were conducted. Primary outcomes were geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers. RESULTS: GMTs to A/H1N1, A/H3N2 and B/Victoria increased following both ccIIV and LAIV and to B/Yamagata following ccIIV (p < 0.05). The GMFR range was 2.4-3.0 times higher for ccIIV4 than for LAIV4 (p < 0.001). Within vaccine types, egg-grown A/H3N2 GMTs were higher (p < 0.05) than cell-grown GMTs [ccIIV4 day 28: egg = 205 (95% CI: 178-237); cell = 136 (95% CI:113-165); LAIV4 day 28: egg = 96 (95% CI: 83-112); cell = 63 (95% CI: 58-74)]. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar. Pre-vaccination titers inversely predicted GMFR. CONCLUSION: The HAI response to ccIIV4 was greater than LAIV4 in this study of mostly older children, and day 0 HAI titers inversely predicted GMFR for both vaccines. Lower prevaccination titers were associated with greater GMFR in both vaccine groups. |
The impact of physical frailty on the response to inactivated influenza vaccine in older adults
Moehling KK , Zhai B , Schwarzmann WE , Chandran UR , Ortiz M , Nowalk MP , Nace D , Lin CJ , Susick M , Levine MZ , Alcorn JF , Zimmerman RK . Aging (Albany NY) 2020 12 (24) 24633-24650 Physical frailty's impact on hemagglutination inhibition antibody titers (HAI) and peripheral blood mononuclear cell (PBMC) transcriptional responses after influenza vaccination is unclear. Physical frailty was assessed using the 5-item Fried frailty phenotype in 168 community- and assisted-living adults ≥55 years of age during an observational study. Blood was drawn before, 3, 7, and 28 days post-vaccination with the 2017-2018 inactivated influenza vaccine. HAI response to the A/H1N1 strain was measured at Days 0 and 28 using seropositivity, seroconversion, log(2) HAI titers, and fold-rise in log(2) HAI titers. RNA sequencing of PBMCs from Days 0, 3 and 7 was measured in 28 participants and compared using pathway analyses. Frailty was not significantly associated with any HAI outcome in multivariable models. Compared with non-frail participants, frail participants expressed decreased cell proliferation, metabolism, antibody production, and interferon signaling genes. Conversely, frail participants showed elevated gene expression in IL-8 signaling, T-cell exhaustion, and oxidative stress pathways compared with non-frail participants. These results suggest that reduced effectiveness of influenza vaccine among older, frail individuals may be attributed to immunosenescence-related changes in PBMCs that are not reflected in antibody levels. |
A randomized controlled trial of antibody response to 2018-19 cell-based vs. egg-based quadrivalent inactivated influenza vaccine in children
Moehling KK , Zimmerman RK , Nowalk MP , Jeng Lin C , Martin JM , Alcorn JF , Susick M , Burroughs A , Holiday C , Flannery B , Levine MZ . Vaccine 2020 38 (33) 5171-5177 BACKGROUND: Current influenza vaccine effectiveness (VE) improvement efforts focus on minimizing egg adaptation mutations during manufacture. This study compared immune response of two FDA-approved quadrivalent inactivated influenza vaccines in an unblinded randomized controlled trial. METHODS: Participants were 144 community dwelling, healthy children/adolescents aged 4-20 years, randomized 1:1 in blocks of 4 to a vaccine grown in cell culture (ccIIV4 [Flucelvax(R)]; n = 85); or in egg medium (IIV4 [Fluzone (R)]; n = 83). Blood was drawn at day 0 prevaccination and at day 28 (19-35 days) post vaccination. Hemagglutination inhibition (HI) assays against A/H1N1 and both B strains and microneutralization (MN) assays against egg-based and cell-based A/H3N2 strains were conducted. The primary outcome measure was seroconversion (day 28/day 0 titer ratio >/= 4 with day 28 titer >/= 40). Secondary outcomes were elevated titers (day 28 HI titer >/= 1:110), geometric mean titers (GMTs) and mean fold rise (MFR) in titers. Outcomes were compared for 74 ccIIV4 recipients and 70 IIV4 recipients, and for those vaccinated and unvaccinated the previous year. Only the HI and MN laboratory analysis team was blinded to group assignment. RESULTS: In this racially diverse (81% non-white) group of children with a median age of 14 years, baseline demographics did not differ between vaccine groups. At day 0, half or more in each vaccine group had elevated HI or MN titers. Low seroconversion rates (14%-35%) were found; they did not differ between groups. Among 2018-19 ccIIV4 recipients, those unvaccinated in the previous season showed significantly higher MFR against A/H1N1 and A/H3N2 cell-grown virus than the previously vaccinated. Similar results were found for MFR against B/Victoria among 2018-2019 IIV4 recipients. CONCLUSION: In mostly older children with high baseline titers, no differences in seroconversion or other measures of antibody titers were found between ccIIV4 and IIV4 recipients against egg- and cell-grown influenza vaccine viruses. CLINICAL TRIALS NO: NCT03614975. |
Development of noise controls for longwall shearer cutting drums
Camargo HE , Azman AS , Alcorn L . Noise Control Eng J 2016 64 (5) 573-585 Noise-induced hearing loss is the second most pervasive disease in the mining industry. The exposure of miners to noise levels above the permissible exposure level results in hearing loss of approximately 80% of coal miners by retirement age. In addition, between 2002 and 2011, approximately 48% of longwall shearer operators were overexposed in coal mines in the United States. Previous research identified the two rotating cutting drums used by the longwall shearer to extract coal as the most significant sound-radiating components. In this context, the National Institute for Occupational Safety and Health conducted research to develop noise controls for longwall mining systems. To this end, structural and acoustic numerical models of a single cutting drum were developed to assess its dynamic and acoustic response, respectively. Once validated, these models were used to explore various noise control concepts including force isolation, varying structural damping and varying component stiffness. Upon multiple simulations, it was determined that structural modifications to increase the stiffness of the outer vane plates were the most practical and durable approach to reduce the sound radiated by the cutting drums. Furthermore, these modifications did not adversely affect the cutting performance, nor the loading ability of the drums. As a result, these structural modifications were implemented into an actual set of drums for evaluation purposes. Results from the underground evaluation, when the modified cutting drums were used under normal operation conditions, showed noise reduction across the entire frequency spectrum with an overall noise reduction of 3 dB in the sound pressure level at the operator location, confirming the validity of the developed noise controls. |
Evaluations of a noise control for roof bolting machines
Azman AS , Yantek DS , Alcorn lA . Min Eng 2012 64 (12) 64-70 In collaboration with Kennametal Inc. and Corry Rubber Corporation, the U.S. National Institute for Occupational Safety and Health (NIOSH) developed a drill bit isolator to address noise overexposures associated with roof bolting machines in underground coal mines. NIOSH laboratory studies confirmed that the drill bit isolator reduces noise during drilling. Field studies were needed to confirm that a noise reduction could be obtained under working conditions and that the device was sufficiently durable. This paper reports results of field tests of the device conducted at five underground coal mines. Noise reduction was assessed by comparing the operator’s noise exposure during drilling with and without the drill bit isolator. Durability was assessed by recording the number of holes and total feet drilled with each bit isolator until either the test period ended or the device failed. The results from these tests showed that the device is an effective noise control in a mine environment. The field-tested drill bit isolators provided a noise reduction of 3-5 dB(A). Of nine devices tested for durability, five exceeded 610 m (2,000 ft) drilled and two exceeded 762 m (2,500 ft) drilled before failure. Durability issues found in the field tests led to final production optimizations that have resulted in a commercially available product for drilling with 35-mm- (1.3-in.-) diameter roof bits and hexagonal drill steels. |
- Page last reviewed:Feb 1, 2024
- Page last updated:May 13, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure