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Inflammatory Mediator Expression Associated With Antibody Response Induced by Live Attenuated vs Inactivated Influenza Virus Vaccine in Children.

ABSTRACT: Background:The reasons for differences in vaccine effectiveness between live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) are not clear. Methods:Blood samples were obtained before vaccination and at days 7 and 21 postvaccination with 2015-2016 quadrivalent IIV or LAIV. Serologic response to the vaccine was measured by hemagglutination inhibition assay. Targeted RNA sequencing and serum cytokine analysis were performed. Paired analyses were used to determine gene expression and were compared between IIV and LAIV recipients. Classification And Regression Trees analysis (CART) identified the strongest associations with vaccine response. Results:Forty-six enrollees received IIV, and 25 received LAIV. The mean age was 11.5 (±3.7) years. Seroconversion with IIV was associated with changes in expression of PRKRA and IFI6. Nonseroconversion for both IIV and LAIV was characterized by increased interferon-stimulated gene expression. Seroprotection with both vaccines was associated with altered expression of CXCL2 and CD36. For LAIV, CART showed that changes in expression of CD80, CXCL2, and CASP1 were associated with seroprotection. Serum cytokines showed that IIV seroconversion was associated with decreased CCL3. LAIV seroprotection tracked with decreased tumor necrosis factor-? and interferon-?. Conclusions:Distinct markers of seroconversion and seroprotection against IIV and LAIV were identified using immunophenotyping and CART analysis.

SUBMITTER: Martin JM

PROVIDER: S-EPMC6262113 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Inflammatory Mediator Expression Associated With Antibody Response Induced by Live Attenuated vs Inactivated Influenza Virus Vaccine in Children.

Martin Judith M JM Avula Raghunandan R Nowalk Mary Patricia MP Lin Chyongchiou Jeng CJ Horne William T WT Chandran Uma R UR Nagg Jennifer P JP Zimmerman Richard K RK Cole Kelly S KS Alcorn John F JF

Open forum infectious diseases 20181024 11

<h4>Background</h4>The reasons for differences in vaccine effectiveness between live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) are not clear.<h4>Methods</h4>Blood samples were obtained before vaccination and at days 7 and 21 postvaccination with 2015-2016 quadrivalent IIV or LAIV. Serologic response to the vaccine was measured by hemagglutination inhibition assay. Targeted RNA sequencing and serum cytokine analysis were performed. Paired analyses were used to de ...[more]

PMID: 30515427

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Project description:LAIV and TIV are effective for prevention of influenza infection in children, but the mechanisms associated with protection are still not well defined. We analyzed the differences in B cell responses and transcriptional profiles. Compared to baseline, LAIV elicited a significant increase in naM-CM-/ve, memory and transitional B cells on day 30, while vaccination with TIV elicited an increase in number of plasmablasts on day 7. Antibody titers against the three vaccine strains (H1N1, H3N2 and B) were significantly higher in the TIV group and correlated with number of antibody-secreting cells. Regarding transcriptional profiles, both vaccines induced expression of interferon signaling, but at different time points, TIV on 1 day, and LAIV on day 7 day post-vaccination, the last only in children younger than 5 years old. Interferon-related genes over expressed in both vaccinated groups correlated with antibody titers of H3N2 vaccines strain. These results suggest that LAIV and TIV induced significant different B cell responses in vaccinated children. Early induction on interferon genes appears important for development of effective antibody responses. Longitudinal study with time points at baseline (day 0), 24hr, day 7 and day 30. 136 total samples analyzed. This was a prospective cohort of previously healthy children 6 months to 14 years of age enrolled between October 2011 and February 2012. Thirty seven subjects were randomized to receive one dose of either LAIV (FluMistM-BM-., MedImmune) (n= 20) or TIV (FluzoneM-BM-., Sanofi Pasteur) (n= 17). Two exceptions were applied to the randomization: four children with ages between 6 months and 2 years old received TIV, since LAIV is not licensed on this age group, and four children with controlled asthma also received TIV following CDCM-bM-^@M-^Ys recommendations. One child aged 6 months at the time of enrollment received two doses of the vaccine with one month interval apart, since it was his first influenza vaccination. Exclusion criteria included any medical comorbidities or chronic conditions (lung, kidney or heart disease), use of systemic steroids in the previous 2 weeks, and congenital or acquired immunodeficiencies. The 2011-2012 LAIV and TIV vaccines contained A/California/7/2009 (H1N1)-like, A/Perth/16/2009 (H3N2)-like and B/Brisbane/60/2008-like antigens, the same strains used on the 2010-2011 influenza vaccine. TIV recipients aged 6 to 35 months old received 0.25 mL intramuscularly and recipients aged 36 months and older received 0.5 mL. LAIV recipients received 0.2 mL by intranasal route, 0.1 mL per nostril. Blood samples were collected at four time points, on day zero prior to vaccination, and day 1, day 7 (range 6-8) and day 30 (range 27-33) post-vaccination.

Project description:ImportanceSome studies have reported negative effects of prior-season influenza vaccination. Prior-season influenza vaccination effects on vaccine effectiveness (VE) in children are not well understood.ObjectiveTo assess the association of prior-season influenza vaccination with subsequent VE in children aged 2 to 17 years.Design, setting, and participantsThis multiseason, test-negative case-control study was conducted in outpatient clinics at 4 US sites among children aged 2 to 17 years with a medically attended febrile acute respiratory illness. Participants were recruited during the 2013-2014, 2014-2015, and 2015-2016 seasons when influenza circulated locally. Cases were children with influenza confirmed by reverse-transcription polymerase chain reaction. Test-negative control individuals were children with negative test results for influenza.ExposuresVaccination history, including influenza vaccine type received in the enrollment season (live attenuated influenza vaccine [LAIV], inactivated influenza vaccine [IIV], or no vaccine) and season before enrollment (LAIV, IIV, or no vaccine), determined from medical records and immunization registries.Main outcomes and measuresLAIV and IIV effectiveness by influenza type and subtype (influenza A[H1N1]pdm09, influenza A[H3N2], or influenza B), estimated as 100 × (1 - odds ratio) in a logistic regression model with adjustment for potential confounders. Prior season vaccination associations were assessed with an interaction term.ResultsOf 3369 children (1749 [52%] male; median age, 6.6 years [range, 2-17 years]) included in the analysis, 772 (23%) had a positive test result for influenza and 1674 (50%) were vaccinated in the enrollment season. Among LAIV recipients, VE against influenza A(H3N2) was higher among children vaccinated in both the enrollment and 1 prior season (50.3% [95% CI, 17.0% to 70.2%]) than among those without 1 prior season vaccination (-82.4% [95% CI, -267.5% to 9.5%], interaction P < .001). The effectiveness of LAIV against influenza A(H1N1)pdm09 was not associated with prior season vaccination among those with prior season vaccination (47.5% [95% CI, 11.4% to 68.9%]) and among those without prior season vaccination (7.8% [95% CI, -101.9% to 57.9%]) (interaction P = .37). Prior season vaccination was not associated with effectiveness of IIV against influenza A(H3N2) (38.7% [95% CI, 6.8% to 59.6%] among those with prior-season vaccination and 23.2% [95% CI, -38.3% to 57.4%] among those without prior-season vaccination, interaction P = .16) or with effectiveness of IIV against influenza A[H1N1]pdm09 (72.4% [95% CI, 56.0% to 82.7%] among those with prior season vaccination and 67.5% [95% CI, 32.1% to 84.4%] among those without prior season vaccination, interaction P = .93). Residual protection from prior season vaccination only (no vaccination in the enrollment season) was observed for influenza B (LAIV: 60.0% [95% CI, 36.8% to 74.7%]; IIV: 60.0% [36.9% to 74.6%]). Similar results were observed in analyses that included repeated vaccination in 2 and 3 prior seasons.Conclusions and relevanceInfluenza VE varied by influenza type and subtype and vaccine type, but prior-season vaccination was not associated with reduced VE. These findings support current recommendations for annual influenza vaccination of children.

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Inflammatory Mediator Expression Associated With Antibody Response Induced by Live Attenuated vs Inactivated Influenza Virus Vaccine in Children.

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Inflammatory Mediator Expression Associated With Antibody Response Induced by Live Attenuated vs Inactivated Influenza Virus Vaccine in Children.

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