Inactivated Influenza Vaccine Recipients Research Articles

Prime-pull vaccination with a plant-derived virus-like particle influenza vaccine elicits a broad immune response and protects aged mice from death and frailty after challenge

BackgroundAdministered intramuscularly (IM), plant-derived, virus-like-particle (VLP) vaccines based on the influenza hemagglutinin (HA) protein elicit both humoral and cellular responses that can protect aged mice from lethal challenge. Unlike split virus vaccines, VLPs can be administered by different routes including intranasally (IN). We evaluated novel vaccine strategies such as prime-pull (IM boosted by IN) and multi-modality vaccination (IM and IN given simultaneously). We wished to determine if these approaches would provide better quality protection in old mice after less severe (borderline-lethal) challenge (ie: immunogenicity, frailty and survival).ResultsSurvival rates were similar in all vaccinated groups. Antibody responses were modest in all groups but tended to be higher in VLP groups compared to inactivated influenza vaccine (IIV) recipients. All VLP groups had higher splenocyte T cell responses than the split virus group. Lung homogenate chemokine/cytokine levels and virus loads were lower in the VLP groups compared to IIV recipients 3 days after challenge (p < 0.05 for viral load vs all VLP groups combined). The VLP-vaccinated groups also had less weight loss and recovered more rapidly than the IIV recipients. There was limited evidence of an immunologic or survival advantage with IN delivery of the VLP vaccine.ConclusionCompared to IIV, the plant-derived VLP vaccine induced a broader immune response in aged mice (cellular and humoral) using either traditional (IM/IM) or novel schedules (multi-modality, prime-pull).

Effect of Previous-Season Influenza Vaccination on Serologic Response in Children During 3 Seasons, 2013-2014 Through 2015-2016.

BackgroundThe effects of repeated influenza vaccination in children are not well understood. In this study, we evaluated previous vaccination effects on antibody response after vaccination with trivalent inactivated influenza vaccine (IIV) or quadrivalent live-attenuated influenza vaccine (LAIV) among school-aged children (5–17 years) across 3 seasons.MethodsChildren were enrolled in the fall of 2013, 2014, and 2015. The participants received IIV or LAIV according to parent preference (2013–2014) or our randomization scheme (2014–2015). All study children received IIV in 2015–2016. Hemagglutination-inhibition assays measured antibody response to egg-grown vaccine strains from prevaccination and postvaccination serum samples. Geometric mean titers (GMTs) and increases in GMTs from before to after vaccination (geometric mean fold rise [GMFR]) were estimated from repeated-measures linear mixed models.ResultsWe enrolled 161 children in 2013–2014, 128 in 2014–2015, and 126 in 2015–2016. Among the IIV recipients, responses to the influenza A(H1N1)pdm09 and B vaccine strains were lowest among children who had received a previous-season IIV. The GMFRs for strains A(H1N1)pdm09 and B were 1.5 to 2.3 for previous-season IIV and 4.3 to 12.9 for previous-season LAIV or no previous vaccine. GMFRs were lower for strain A(H3N2), and differences according to previous-season vaccination history were smaller and not significant in most seasons. Most children had a post-IIV vaccination titer of ≥40 for vaccine strains in all seasons, regardless of previous-season vaccination history. Little to no increase in antibody levels was observed after vaccination with LAIV.ConclusionsSerologic response to vaccination was greatest for IIV, but previous-season vaccination modified IIV response to A(H1N1)pdm09 and B. Influenza A(H3N2) responses were low in all groups, and LAIV generated minimal serologic response against all strains.

Live Attenuated and Inactivated Influenza Vaccine Effectiveness.

Researchers in observational studies of vaccine effectiveness (VE) in which they compared quadrivalent live attenuated vaccine (LAIV4) and inactivated influenza vaccine (IIV) among children and adolescents have shown inconsistent results, and the studies have been limited by small samples. We combined data from 5 US studies from 2013-2014 through 2015-2016 to compare the VE of LAIV4 and IIV against medically attended, laboratory-confirmed influenza among patients aged 2 to 17 years by influenza season, subtype, age group, and prior vaccination status. The VE of IIV or LAIV4 was calculated as 100% × (1 - odds ratio), comparing the odds of vaccination among patients who were influenza-positive to patients who were influenza-negative from adjusted logistic regression models. Relative effectiveness was defined as the odds of influenza comparingLAIV4 and IIV recipients. Of 17 173 patients aged 2 to 17 years, 4579 received IIV, 1979 received LAIV4, and 10 615 were unvaccinated. Against influenza A/H1N1pdm09, VE was 67% (95% confidence interval [CI]: 62% to 72%) for IIV and 20% (95% CI: -6% to 39%) for LAIV4. Results were similar when stratified by vaccination in the previous season. LAIV4 recipients had significantly higher odds of influenza A/H1N1pdm09 compared with IIV recipients (odds ratio 2.66; 95% CI: 2.06 to 3.44). LAIV4 and IIV had similar effectiveness against influenza A/H3N2 and B. Our overall findings were consistent when stratified by influenza season and age group. From this pooled individual patient-level data analysis, we found reduced effectiveness of LAIV4 against influenza A/H1N1pdm09 compared with IIV, which is consistent with published results from the individual studies included.

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

BackgroundThe reasons for differences in vaccine effectiveness between live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) are not clear.MethodsBlood 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.ResultsForty-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–α and interferon-γ.ConclusionsDistinct markers of seroconversion and seroprotection against IIV and LAIV were identified using immunophenotyping and CART analysis.

Effectiveness of Live Attenuated vs Inactivated Influenza Vaccines in Children During the 2012-2013 Through 2015-2016 Influenza Seasons in Alberta, Canada

Recent observational studies report conflicting results regarding the effectiveness of live attenuated influenza vaccine (LAIV), particularly against influenza A(H1N1)pdm09. To compare the effectiveness of LAIV and inactivated influenza vaccine (IIV) against laboratory-confirmed influenza. A test-negative study to estimate influenza vaccine effectiveness (VE) using population-based, linked, individual-level laboratory, health administrative, and immunization data. Data were obtained from 10 169 children and adolescents aged 2 to 17 years (children) who were tested for influenza in inpatient or outpatient settings during periods when influenza was circulating based on a threshold level of 5% weekly test positivity for the province during the 4 influenza seasons spanning from November 11, 2012, to April 30, 2016, in Alberta, Canada. Logistic regression was used to estimate VE by vaccine type, influenza season, and influenza type and subtype. The relative effectiveness of each vaccine type was assessed by comparing the odds of laboratory-confirmed influenza infection for LAIV recipients with that for IIV recipients. The primary exposure was receipt of LAIV or IIV before testing for influenza. The primary outcome was influenza case status as determined by reverse-transcriptase polymerase chain reaction testing. A total of 10 779 respiratory specimens (from 10 169 children) collected and tested for influenza during the 4 influenza seasons were included, with 53.4% from males; the mean (SD) age was 7.0 (4.6) years. Across the 4 influenza seasons, 3161 children tested positive for influenza. Combining the 4 influenza seasons, the adjusted VE against influenza A(H1N1)pdm09 was 69% (95% CI, 56%-78%) for LAIV compared with 79% (95% CI, 70%-86%) for IIV. Vaccine effectiveness against influenza A(H3N2) was 36% (95% CI, 14%-53%) for LAIV and 43% (95% CI, 22%-59%) for IIV. Against influenza B, VE was 74% (95% CI, 62%-82%) for LAIV and 56% (95% CI, 41%-66%) for IIV. There were no significant differences in the odds of influenza infection for LAIV recipients compared with IIV recipients except for influenza B during the 2015-2016 season, when LAIV recipients had lower odds of infection than IIV recipients (odds ratio, 0.36; 95% CI, 0.17-0.76). There was no evidence to support the lack of effectiveness of LAIV against influenza A(H1N1)pdm09. These results support administration of either vaccine type in this age group.

Vaccine failure and serologic response to live attenuated and inactivated influenza vaccines in children during the 2013–2014 season

BackgroundRecent observational studies in the United States indicated live attenuated influenza vaccine (LAIV) was less effective in children against clinical influenza infection caused by A(H1N1)pdm09 relative to inactivated influenza vaccine (IIV). During the 2013–2014 influenza season, we conducted an observational study among children aged 5–17 years to compare serologic responses to LAIV and IIV and explore factors associated with vaccine failure. MethodsOne hundred and sixty-one children received one dose of trivalent IIV or quadrivalent LAIV according to parental preference. Baseline and postvaccination serum samples were tested with hemagglutination inhibition (HI) assays against vaccine reference strains. Geometric mean titers (GMT), geometric mean fold rise (GMFR), seroconversion, and seroprotection (HI titer ≥ 40) were used to assess response to vaccine. Active surveillance for acute respiratory illness was conducted during the influenza season and influenza cases were confirmed by reverse transcription polymerase chain reaction (RT-PCR). Logistic regression was used to examine the association between vaccine type and vaccine failure. ResultsLAIV and IIV recipients were similar with respect to demographics and baseline GMT for each vaccine strain. RT-PCR confirmed influenza (vaccine failure) occurred in 8 (13%) of 62 LAIV recipients and 3 (3%) of 99 IIV recipients (p = .02). Postvaccination GMFR for A(H1N1)pdm09 was higher for IIV vs LAIV receipt (GMFR 3.3 vs. 0.8, p < .0001). Postvaccination titers against A(H1N1)pdm09 were ≥40 for 91% and 44% of IIV and LAIV recipients, respectively (p < .0001). Among 13 IIV and 18 LAIV recipients with seronegative baseline titer against A(H1N1pdm09), 54% and 0% seroconverted, respectively. LAIV receipt was the only factor associated with A(H1N1)pdm09 vaccine failure in the age-adjusted multivariable model (odds ratio 4.5, 95% CI 1.1–18.2). ConclusionReceipt of LAIV generated minimal HI antibody response in children, including among those seronegative at baseline. LAIV recipients had significant increased risk of A(H1N1)pdm09 infection compared to IIV recipients.

Differential gene expression elicited by children in response to the 2015-16 live attenuated versus inactivated influenza vaccine.

In recent influenza seasons, the live attenuated influenza vaccine (LAIV) has not demonstrated the same level of vaccine effectiveness as that observed among children who received the inactivated influenza vaccine (IIV). To better understand this difference, this study compared the mRNA sequencing transcription profile (RNA seq) in children who received either IIV or LAIV. Children 3-17years of age receiving quadrivalent influenza vaccine were enrolled. Blood samples were collected on Day 0 prior to vaccination and again on Day 7 (range 6-10days) following vaccination. Total RNA was isolated from PAXgene tubes and sequenced for a custom panel of 89 transcripts using the TruSeq Targeted RNA Expression method. Fold differences in normalized RNA seq counts from Day 0 to Day 7 were calculated, log2 transformed and compared between the two vaccine groups. Of 72 children, 46 received IIV and 26 received LAIV. Following IIV vaccination, 7 genes demonstrated significant differential expression at Day 7 (down-regulated). In contrast, following LAIV vaccination, 8 genes demonstrated significant differential expression at Day 7 (5 up-regulated and 3 down-regulated). Only two genes demonstrated similar patterns of regulation in both groups. Differential regulation of genes was observed between 2015-16 LAIV and IIV recipients. These results help to elucidate the immune response to influenza vaccines and may be related to the difference in vaccine effectiveness observed in recent years between LAIV and IIV.

2015-2016 Vaccine Effectiveness of Live Attenuated and Inactivated Influenza Vaccines in Children in the United States.

In the 2015-2016 season, quadrivalent live attenuated influenza vaccine (LAIV) and both trivalent and quadrivalent inactivated influenza vaccine (IIV) were available in the United States. This study, conducted according to a test-negative case-control design, enrolled children aged 2-17 years presenting to outpatient settings with fever and respiratory symptoms for <5 days at 8 sites across the United States between 30 November 2015 and 15 April 2016. A nasal swab was obtained for reverse-transcriptase polymerase chain reaction (RT-PCR) testing for influenza, and influenza vaccination was verified in the medical record or vaccine registry. Influenza vaccine effectiveness (VE) was estimated using a logistic regression model. Of 1012 children retained for analysis, most children (59%) were unvaccinated, 10% received LAIV, and 31% received IIV. Influenza A (predominantly antigenically similar to the A/California/7/2009 strain) was detected in 14% and influenza B (predominantly a B/Victoria lineage) in 10%. For all influenza, VE was 46% (95% confidence interval [CI], 7%-69%) for LAIV and 65% (48%-76%) for IIV. VE against influenza A(H1N1)pdm09 was 50% (95% CI, -2% to 75%) for LAIV and 71% (51%-82%) for IIV. The odds ratio for vaccine failure with RT-PCR-confirmed A(H1N1)pdm09 was 1.71 (95% CI, 0.78-3.73) in LAIV versus IIV recipients. LAIV and IIV demonstrated effectiveness against any influenza among children aged 2-17 years in 2015-2016. When compared to all unvaccinated children, VE against influenza A(H1N1)pdm09 was significant for IIV but not LAIV. NCT01997450.

Differential Gene Expression Elicited by Children in Response to the 2015–2016 Live Attenuated vs. Inactivated Influenza Vaccine

BackgroundIn recent influenza seasons, the live attenuated influenza vaccine (LAIV) has not demonstrated the same level of vaccine effectiveness as that observed among children who received the inactivated influenza vaccine (IIV). To better understand this difference, this study compared the mRNA sequencing transcription profile (RNA seq) in children who received either IIV or LAIV.MethodsChildren 3–17 years of age receiving quadrivalent influenza vaccine were enrolled. Blood samples were collected on Day 0 prior to vaccination and again on Day 7 (range 6–10 days) following vaccination. Total RNA was isolated from PAXgene tubes and sequenced for a custom panel of 89 transcripts using the TruSeq Targeted RNA Expression method. Fold differences in normalized RNA seq counts from Day 0 to Day 7 were calculated, log2 transformed and compared between the two vaccine groups.ResultsOf 73 children, 47 received IIV and 26 received LAIV. Following IIV vaccination, 12 genes demonstrated significant differential expression at Day 7. In contrast, following LAIV vaccination, seven genes demonstrated significant differential expression at Day 7, five of which were not differentially expressed by IIV. Two genes demonstrated similar patterns of regulation in both IIV and LAIV recipients.ConclusionDifferential regulation of genes was observed between 2015 and 2016 LAIV and IIV recipients. These results help to elucidate the immune response to influenza vaccines and might help explain the difference in vaccine effectiveness observed in recent years between LAIV and IIV.Disclosures R. Zimmerman, sanofi pasteur: Grant Investigator, Research grant Merck & Co, Inc.: Grant Investigator, Research grant Pfizer, Inc.: Grant Investigator, Research grant; C. J. Lin, Sanofi: Grant Investigator, Research grant Merck & Co, Inc.: Grant Investigator, Research grant Pfizer, Inc..: Grant Investigator, Research grant; M. P. Nowalk, Merck & Co, Inc.: Grant Investigator, Research grant Pfizer, Inc.: Grant Investigator, Research grant

Impact of Prior Vaccination History on Risk of Vaccine Failure with Live Attenuated and Inactivated Influenza Vaccines in Children, 2013–14 through 2015–16

Abstract Background Prior season vaccination may influence influenza vaccine effectiveness; however, little is known about the impact of prior vaccination or vaccine type received. We assessed prior vaccination history and risk of influenza in children over 3 seasons. Methods Children aged 2–17 years seeking outpatient care for febrile acute respiratory illness were recruited during the 2013–14 through 2015–16 seasons (1 vaccine-mismatched H3N2 season and 2 H1N1pdm09 seasons) at 4 US sites. Influenza was confirmed by RT-PCR. Vaccination data for the season of enrollment (current) and 3 prior seasons were obtained from medical records and immunization registries. Among children who received 1 dose of influenza vaccine during the current season, risk of vaccine failure (ie, PCR-confirmed influenza) was estimated using test-negative design with logistic regression models adjusted for age, season, enrollment site, enrollment week (relative to peak), and outpatient visits. Risk of failure with live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) were modeled separately. Separate models were used for vaccine history based on number of seasons and vaccine type received (ie, none, LAIV, IIV, both). Results Influenza was detected in 191 (12%) of 1601 children who received 1 vaccine dose during the current season: 117 H3N2 and 74 H1N1pdm09. Among 508 current season LAIV recipients, 239 (47%) received LAIV and 144 (28%) received IIV in the prior season. Among 1093 current season IIV recipients, 94 (9%) received LAIV and 711 (65%) received IIV in the prior season. For LAIV, receipt of vaccine (any type) in a prior season was associated with a decreased risk of H3N2 failure (odds ratio 0.23; 95% CI, 0.09–0.57). Prior vaccination was not associated with risk of LAIV vaccine failure against H1N1pdm09. For IIV, there was no evidence that prior vaccination was associated with risk of vaccine failure against H3N2 or H1N1pdm09. Similar results were seen in children without any high-risk conditions. Conclusion Risk of vaccine failure among vaccinated children varied by vaccine type and virus subtype. Future studies should examine immunologic effects to better understand these differences. Disclosures H. Q. McLean, MedImmune: Grant Investigator, Research support; H. Caspard, MedImmune: Employee, Salary; M. R. Griffin, MedImmune: Grant Investigator, Grant recipient; M. Gaglani, MedImmune: Investigator, Research support; T. R. Peters, MedImmune: Investigator, Research support; K. A. Poehling, MedImmune: Investigator, Research support; C. S. Ambrose, AstraZeneca: Employee, Salary; E. Belongia, MedImmune: Grant Investigator, Research support

Safety of quadrivalent live attenuated influenza vaccine in subjects aged 2–49 years

BackgroundQuadrivalent live attenuated influenza vaccine (Q/LAIV) was licensed in 2012 and replaced trivalent live attenuated influenza vaccine in the United States during the 2013–2014 influenza season. This study assessed the safety of Q/LAIV in children and adults aged 2–49years. MethodsThis was a prospective observational cohort study using data collected from Kaiser Permanente Northern California. Post-vaccination events of interest were any hospitalization, hospitalization for lower respiratory tract infection, and the following medically attended events: hypersensitivity, seizures/convulsions, lower respiratory tract infection, wheezing, Guillain-Barré syndrome, Bell’s palsy, encephalitis, neuritis, vasculitis, and narcolepsy/cataplexy. The rates of these events during the risk interval post-vaccination were compared with rates observed during reference periods later in the follow-up (within-cohort analysis) and with rates observed in frequency-matched unvaccinated controls and inactivated influenza vaccine (IIV) recipients. ResultsA total of 62,040 eligible Q/LAIV recipients were identified during the 2013–2014 influenza season. Within-cohort comparisons of all Q/LAIV recipients as well as comparisons between Q/LAIV recipients and unvaccinated controls or IIV recipients did not show any significantly higher risk of hospitalizations or medically attended events following administration of Q/LAIV. Additional analyses by setting (clinic visits, emergency department visits, and hospital admissions) and age group (2–4, 5–8, 9–17, and 18–49years) also did not reveal clinically consistent findings that suggested any increased risk after administration of Q/LAIV. ConclusionIn this large population study of individuals aged 2–49years, no safety signals associated with the administration of Q/LAIV were observed. A much larger study population would be needed to confidently reject any association between Q/LAIV and very rare events, specifically those with an incidence of <1 event/10,000 person-years.Trial registration: ClinicalTrials.gov NCT01985997

Neutralizing Antibody Responses to Antigenically Drifted Influenza A(H3N2) Viruses among Children and Adolescents following 2014-2015 Inactivated and Live Attenuated Influenza Vaccination.

Human influenza A(H3N2) viruses that predominated during the moderately severe 2014-2015 influenza season differed antigenically from the vaccine component, resulting in reduced vaccine effectiveness (VE). To examine antibody responses to 2014-2015 inactivated influenza vaccine (IIV) and live-attenuated influenza vaccine (LAIV) among children and adolescents, we collected sera before and after vaccination from 150 children aged 3 to 17 years enrolled at health care facilities. Hemagglutination inhibition (HI) assays were used to assess the antibody responses to vaccine strains. We evaluated cross-reactive antibody responses against two representative A(H3N2) viruses that had antigenically drifted from the A(H3N2) vaccine component using microneutralization (MN) assays. Postvaccination antibody titers to drifted A(H3N2) viruses were higher following receipt of IIV (MN geometric mean titers [GMTs], 63 to 68; 38 to 45% achieved seroconversion) versus LAIV (MN GMT, 22; only 3 to 5% achieved seroconversion). In 9- to 17-year-olds, the highest MN titers were observed among IIV-vaccinated individuals who had received LAIV in the previous season. Among all IIV recipients aged 3 to 17 years, the strongest predictor of antibody responses to the drifted viruses was the prevaccination titers to the vaccine strain. The results of our study suggest that in an antigenically drifted influenza season, vaccination still induced cross-reactive antibody responses to drifted circulating A(H3N2) viruses, although higher antibody titers may be required for protection. Antibody responses to drifted A(H3N2) viruses following vaccination were influenced by multiple factors, including vaccine type and preexisting immunity from prior exposure.

Antibody to Influenza Virus Neuraminidase: An Independent Correlate of Protection.

Laboratory correlates of influenza vaccine protection can best be identified by examining people who are infected despite vaccination. While the importance of antibody to viral hemagglutinin (HA) has long been recognized, the level of protection contributed independently by antibody to viral neuraminidase (NA) has not been determined. Sera from a controlled trial of the efficacies of inactivated influenza vaccine (IIV) and live attenuated influenza vaccine (LAIV) were tested by hemagglutination inhibition (HAI) assay, microneutralization (MN) assay, and a newly standardized lectin-based neuraminidase inhibition (NAI) assay. The NAI assay detected a vaccine response in 37% of IIV recipients, compared with 77% and 67% of participants in whom responses were detected by the HAI and MN assays, respectively. For LAIV recipients, the NAI, HAI, and MN assays detected responses in 6%, 21%, and 17%, respectively. In IIV recipients, as NAI assay titers rose, the frequency of infection fell, similar to patterns seen with HAI and MN assays. HAI and MN assay titers were highly correlated, but NAI assay titers exhibited less of a correlation. Analyses suggested an independent role for NAI antibody in protection, which was similar in the IIV, LAIV, and placebo groups. While NAI antibody is not produced to a large extent in response to current IIV, it appears to have an independent role in protection. As new influenza vaccines are developed, NA content should be considered. NCT00538512.

Influenza Vaccination of Pregnant Women and Protection of Their Infants

Madhi SA, Cutland CL, Kuwanda L. Influenza vaccination of pregnant women and protection of their infants. N Engl J Med 2014; 371:918–31. Pregnant women are at risk for severe influenza from the second trimester to the early postpartum period, making them a priority group for seasonal influenza vaccination. Because pregnancy is characterized by the attenuation of cell-mediated immune responses, the efficacy of the inactivated influenza vaccine (IIV) in pregnant women may differ from that in nonpregnant women. Nevertheless, to date, no controlled trials have been performed to evaluate the efficacy of IIV during pregnancy. Furthermore, the vaccination of pregnant women may also confer partial protection against confirmed influenza in their infants. However, observational studies have had conflicting results with regard to the efficacy of the trivalent IIV during pregnancy in protecting infants against respiratory illness. The aim of this study was to evaluate the immunogenicity, safety, and efficacy of IIV in pregnant women and their infants until 24 weeks after birth. The authors performed 2 randomized, double-blind, placebo-controlled trials of trivalent IIV in pregnant women with and without human immunodeficiency virus (HIV). Healthy women aged 18 to 38 years with an estimated gestational age of 20 to 36 weeks were enrolled at 1 of 4 antenatal clinics in South Africa during the 2011 and 2012 influenza seasons. HIV-infected women who met these same eligibility criteria were enrolled during 2011. Participants were randomly assigned in a 1:1 ratio to receive IIV or placebo. Active surveillance for influenzalike illness was conducted through weekly contact with the participants. Women and infants identified as having influenza-like illness were tested for influenza virus by means of a reverse transcriptase–polymerase chain reaction (RT-PCR) assay. All the mothers and infants in the HIV-infected cohort and a nested group of uninfected mother–infant dyads were enrolled in an intensive safety and immunogenicity study. Those women were provided with diary cards on which to document for 1 week the possible local and systemic reactions to the vaccination, and blood samples were collected for hemagglutination inhibition (HAI) studies. A total of 2116 HIV-uninfected pregnant women were enrolled (mean age, 26.2 years; mean gestational age, 26.8 weeks) and gave birth to 2049 live infants. In the immunogenicity subset, seroconversion rates for strains A(H1N1), A(H3N2), and B(Victoria) among IIV recipients 1 month after immunization were 72.5%, 64.8%, and 92.3%, respectively; the rates among the placebo recipients were 8.1%, 2.7%, and 2.0%, respectively (P < .001 for all comparisons). Newborns of IIV recipients had higher HAI geometric mean titers for all the vaccine strains than did newborns of the placebo recipients, and they were also more likely to have an HAI titer of 1:40 or higher for A(H1N1) (81.1% vs 34.0%, respectively), A(H3N2) (60.0% vs 17.5%, respectively), and B (82.1% vs 43.7%, respectively) (P < .001 for all comparisons). The attack rate for RT-PCR–confirmed influenza among both the placebo recipients and their infants was 3.6%. The attack rates among IIV recipients and their infants were 1.8% and 1.9%, respectively, and the respective vaccine-efficacy rates were 50.4% (95% confidence interval [CI], 14.5–71.2) and 48.8% (95% CI, 11.6–70.4). A total of 194 HIV-infected women were included (mean maternal age, 28.2 years; mean gestational age, 27.3 weeks; baseline median CD4 T-cell count, 393.5 cells per μL; median level of plasma HIV-1 RNA, 1067 copies per milliliter). The attack rate for the placebo recipients was 17.0%, and the rate for IIV recipients was 7.0%; Literature Review

Distinct Cross-reactive B-Cell Responses to Live Attenuated and Inactivated Influenza Vaccines

The immunological bases for the efficacies of the 2 currently licensed influenza vaccines, live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV), are not fully understood. The goal of this study was to identify specific B-cell responses correlated with the known efficacies of these 2 vaccines. We compared the B-cell and antibody responses after immunization with 2010/2011 IIV or LAIV in young adults, focusing on peripheral plasmablasts 6-8 days after vaccination. The quantities of vaccine-specific plasmablasts and plasmablast-derived polyclonal antibodies (PPAbs) in IIV recipients were significantly higher than those in LAIV recipients. No significant difference was detected in the avidity of vaccine-specific PPAbs between the 2 vaccine groups. Proportionally, LAIV induced a greater vaccine-specific immunoglobulin A plasmablast response, as well as a greater plasmablast response to the conserved influenza nuclear protein, than IIV. The cross-reactive plasmablast response to heterovariant strains, as indicated by the relative levels of cross-reactive plasmablasts and the cross-reactive PPAb binding reactivity, was also greater in the LAIV group. Distinct quantitative and qualitative patterns of plasmablast responses were induced by LAIV and IIV in young adults; a proportionally greater cross-reactive response was induced by LAIV.

The healthcare and societal burden associated with influenza in vaccinated and unvaccinated European and Israeli children

Few data exist regarding the healthcare and societal burden of culture-confirmed influenza illness in European and Israeli children. The current analysis describes this burden in vaccinated and unvaccinated children 2–17 years of age. Healthcare and societal burden outcomes were prospectively collected for culture-confirmed influenza illness in three previous randomized studies: a study of live attenuated influenza vaccine (LAIV) versus placebo in children aged <48 months attending day care (N = 846–973), and studies of LAIV versus inactivated influenza vaccine (IIV) in children aged <72 months with recurrent respiratory infections (N = 1,609) and in children aged 6–17 years with asthma (N = 2,211). The incidence of each endpoint among enrolled subjects and subjects with influenza was determined by treatment group and by country. Among subjects with influenza, 57–91 % missed school or day care, 45–90 % used non-antibiotic medications, 29–55 % of parents missed work, 17–55 % used antibiotics, 11–62 % had additional provider visits, and 9–20 % had acute otitis media. Where evaluated, rates of outcomes were generally similar between countries. Among all children enrolled, LAIV recipients missed 324–902 and 150 fewer days of day care per 1,000 children than those of placebo and IIV recipients, respectively; parents of LAIV recipients missed 197–340 and 76 fewer days of work per 1,000 children than those of placebo and IIV recipients, respectively. Influenza illness in European and Israeli children 2–17 years of age resulted in a considerable absenteeism and healthcare utilization that was similar across the countries studied. These data underscore the potential benefits of annual vaccination of children against influenza.