Efficacy of high-dose versus standard-dose influenza vaccine in older adults.

BACKGROUND: As compared with a standard-dose vaccine, a high-dose, trivalent, inactivated influenza vaccine (IIV3-HD) improves antibody responses to influenza among adults 65 years of age or older. This study evaluated whether IIV3-HD also improves protection against laboratory-confirmed influenza illness. METHODS: We conducted a phase IIIb-IV, multicenter, randomized, double-blind, active-controlled trial to compare IIV3-HD (60 µg of hemagglutinin per strain) with standard-dose trivalent, inactivated influenza vaccine (IIV3-SD [15 µg of hemagglutinin per strain]) in adults 65 years of age or older. Assessments of relative efficacy, effectiveness, safety (serious adverse events), and immunogenicity (hemagglutination-inhibition [HAI] titers) were performed during the 2011-2012 (year 1) and the 2012-2013 (year 2) northern-hemisphere influenza seasons. RESULTS: A total of 31,989 participants were enrolled from 126 research centers in the United States and Canada (15,991 were randomly assigned to receive IIV3-HD, and 15,998 to receive IIV3-SD). In the intention-to-treat analysis, 228 participants in the IIV3-HD group (1.4%) and 301 participants in the IIV3-SD group (1.9%) had laboratory-confirmed influenza caused by any viral type or subtype associated with a protocol-defined influenza-like illness (relative efficacy, 24.2%; 95% confidence interval [CI], 9.7 to 36.5). At least one serious adverse event during the safety surveillance period was reported by 1323 (8.3%) of the participants in the IIV3-HD group, as compared with 1442 (9.0%) of the participants in the IIV3-SD group (relative risk, 0.92; 95% CI, 0.85 to 0.99). After vaccination, HAI titers and seroprotection rates (the percentage of participants with HAI titers ≥ 1:40) were significantly higher in the IIV3-HD group. Conclusions: Among persons 65 years of age or older, IIV3-HD induced significantly higher antibody responses and provided better protection against laboratory-confirmed influenza illness than did IIV3-SD. (Funded by Sanofi Pasteur; ClinicalTrials.gov number, NCT01427309.).

Addressing a Yellow Fever Vaccine Shortage - United States, 2016-2017.

Recent manufacturing problems resulted in a shortage of the only U.S.-licensed yellow fever vaccine. This shortage is expected to lead to a complete depletion of yellow fever vaccine available for the immunization of U.S. travelers by mid-2017. CDC, the Food and Drug Administration (FDA), and Sanofi Pasteur are collaborating to ensure a continuous yellow fever vaccine supply in the United States. As part of this collaboration, Sanofi Pasteur submitted an expanded access investigational new drug (eIND) application to FDA in September 2016 to allow for the importation and use of an alternative yellow fever vaccine manufactured by Sanofi Pasteur France, with safety and efficacy comparable to the U.S.-licensed vaccine; the eIND was accepted by FDA in October 2016. The implementation of this eIND protocol included developing a systematic process for selecting a limited number of clinic sites to provide the vaccine. CDC and Sanofi Pasteur will continue to communicate with the public and other stakeholders, and CDC will provide a list of locations that will be administering the replacement vaccine at a later date.

Effect of Previous-Year Vaccination on the Efficacy, Immunogenicity, and Safety of High-Dose Inactivated Influenza Vaccine in Older Adults.

BACKGROUND: High-dose inactivated influenza vaccine (IIV-HD) is an alternative to the standard-dose inactivated influenza vaccine (IIV-SD) in the United States for influenza prevention in older adults. IIV-HD improved efficacy relative to IIV-SD in a randomized controlled trial. Recent observational studies suggest that previous influenza vaccination may influence the immunogenicity and effectiveness of current-season vaccination. METHODS: The original study was a double-blind, randomized trial comparing IIV-HD to IIV-SD in adults aged ≥65 years over 2 influenza seasons. A subset of year 1 (Y1) participants reenrolled in year 2 (Y2), receiving vaccine by random assignment in both years. We evaluated the effect of Y1 vaccination on Y2 relative vaccine efficacy (VE), immunogenicity (hemagglutination inhibition [HAI] titers), and safety among reenrolled participants. RESULTS: Of 14 500 Y1 participants, 7643 reenrolled in Y2. Relative to participants who received IIV-SD both seasons, VE was higher for IIV-HD vaccinees in Y2 (28.3% overall; 25.1% for Y1 IIV-HD, Y2 IIV-HD; and 31.6% for Y1 IIV-SD, Y2 IIV-HD). In multivariate logistic regression models, Y1 vaccine was not a significant modifier of Y2 VE (P= .43), whereas Y2 IIV-HD remained significantly associated with lower influenza risk (P= .043). Compared to administration of IIV-SD in both years, postvaccination HAI titers were significantly higher for patterns that included IIV-HD in Y2. No safety concerns were raised with IIV-HD revaccination. CONCLUSIONS: IIV-HD is likely to provide clinical benefit over IIV-SD irrespective of previous-season vaccination with IIV-HD or IIV-SD. IIV-HD consistently improved immune responses, and no safety concerns emerged in the context of IIV-HD revaccination.

Efficacy and effectiveness of high-dose influenza vaccine in older adults by circulating strain and antigenic match: An updated systematic review and meta-analysis.

BACKGROUND: Influenza vaccine efficacy/effectiveness can vary from season to season due in part to the dominant circulating strains and antigenic matching. This study reviews the relative vaccine efficacy/effectiveness (rVE) of high-dose inactivated trivalent influenza vaccine (HD-IIV3) compared to standard-dose influenza vaccines (SD-IIV) in adults aged ≥ 65 years against influenza-associated outcomes. Additional sub-analyses of HD-IIV3 rVE were performed by the predominantly circulating influenza strain and the antigenic match or mismatch of the vaccine against the predominant circulating strains. METHODS: An updated systematic review and meta-analysis was conducted for studies assessing the rVE of HD-IIV3 against probable/laboratory-confirmed influenza-like illness (ILI), hospital admissions, and death in adults aged ≥ 65 years. Results from individual seasons were extracted from the studies, and viral surveillance data were used to determine the dominant circulating strains and antigenic match for each season. Results were then stratified based on clinical outcomes and seasonal characteristics and meta-analyzed to estimate pooled rVEs of HD-IIV3. RESULTS: 15 publications were meta-analyzed after screening 1,293 studies, providing data on 10 consecutive influenza seasons and over 22 million individuals receiving HD-IIV3 in randomized and observational settings. Across all influenza seasons, HD-IIV3 demonstrated improved protection against ILI compared to SD-IIV (rVE = 15.9%, 95% CI: 4.1-26.3%). HD-IIV3 was also more effective at preventing hospital admissions from all-causes (rVE = 8.4%, 95% CI: 5.7-11.0%), as well as influenza (rVE = 11.7%, 95% CI: 7.0-16.1%), pneumonia (rVE = 27.3%, 95% CI: 15.3-37.6%), combined pneumonia/influenza (rVE = 13.4%, 95% CI: 7.3-19.2%) and cardiorespiratory events (rVE = 17.9%, 95% CI: 15.0-20.8%). Reductions in mortality due to pneumonia/influenza (rVE = 39.9%, 95% CI: 18.6-55.6%) and cardiorespiratory causes (rVE = 27.7%, 95% CI: 13.2-32.0%) were also observed. Similar pooled rVEs were observed in both matched and mismatched seasons and in seasons where A/H3N2 or A/H1N1 strains were predominantly circulating. CONCLUSIONS: Evidence over 10 consecutive influenza seasons and in more than 34 million individuals aged ≥ 65 years suggests that HD-IIV3 is consistently more effective than SD-IIV at reducing influenza cases as well as influenza-associated clinical complications irrespective of circulating strain and antigenic match. A video summary of the article can be accessed via the Supplementary data link at the end of this article.

Hypotonic-hyporesponsive Episodes After Diphtheria, Tetanus and Acellular Pertussis Vaccination.

BACKGROUND: Hypotonic-hyporesponsive episode (HHE) after whole cell pertussis vaccination is a known adverse event. Less is known about the risk of HHE after administration of acellular pertussis vaccines. METHODS: Using parental interviews, this study actively surveyed for HHE among infants after doses 1 and 2 of acellular pertussis vaccine. RESULTS: We interviewed the parents of 52,531 infants. HHE was reported at a rate of 22.8 per 100,000 doses (95% CI: 11.8-39.9) of acellular pertussis vaccine, approximately 45 episodes per 100,000 children. CONCLUSIONS: These rates are lower than HHE rates reported after whole cell pertussis vaccines and within the range of HHE rates reported in other studies of acellular pertussis vaccines.

Introductory paper: High-dose influenza vaccine.

Seasonal influenza has a significant impact on global public health each year, especially in older adults 65 years of age and above. This paper presents the evolution of high-dose influenza vaccine and the quantity as well as quality of evidence on this vaccine. Its introduces other peer-reviewed manuscripts included in this supplement covering the benefits high-dose influenza vaccine over ten consecutive influenza seasons. The development of the high-dose influenza vaccine represents an important step in the evolution of influenza vaccines, offering an advancement in prevention of influenza and a step in encouraging healthy aging in older adults. A video summary of the article can be accessed via the Supplementary data link at the end of this article.

Brand-specific rates of pertussis disease among Wisconsin children given 1-4 doses of pertussis Vaccine, 2010-2014.

BACKGROUND: Acellular pertussis vaccines were initially licensed based on placebo-controlled efficacy trials, but such trials are no longer ethical. The effectiveness of current pertussis vaccines among properly vaccinated children <5 years is so high that a randomized trial is infeasible. Fluctuations in pertussis incidence and characteristics of the US vaccine marketplace make selection of suitable controls for a case-control study problematic. To satisfy an FDA requirement to evaluate rates of pertussis following licensure of Pentacel® vaccine, we used a case-cohort study design with a novel method for characterizing the cohort population. METHODS: This prospective, observational study was conducted in Wisconsin from 2010 to 2014 among Wisconsin residents <60 months of age who received ≤four doses of pertussis vaccine (surveillance population). Cases were identified by the Wisconsin Division of Public Health. Characteristics and pertussis vaccinations of the surveillance population were estimated by ongoing random telephonic survey. The primary objective was to determine rates of pertussis disease among those who received only Pentacel vaccine (Group 1) vs those who received a single brand of vaccine other than Pentacel vaccine (Group 2). RESULTS: 1195 pertussis cases were identified. It was estimated that the surveillance population accrued a total of 1,133,403 person-years (Group 1, 39%; Group 2, 41%; Group 3 [those not in Group 1 or Group 2], 20%). Pertussis rates were similar in Group 1 (98.9/100,000) and Group 2 (96.2/100,000); rate ratios were 1.03 (unadjusted; 90% CI, 0.92-1.15) and 0.99 (adjusted; 90% CI, 0.89-1.12). Persons with one or more delayed vaccinations had a 66% higher risk of pertussis (90% CI, 39-96%). DISCUSSION: Pertussis protection was not found to differ for recipients of the newly licensed vs other available pertussis vaccines. Delayed vaccination substantially increased risk of pertussis. Sample survey methodology was able to characterize the study cohort and enable an otherwise-infeasible study. Clinical Trial Registry number: ClinicalTrials.gov, NCT01129362.

Epidemiology of pertussis and Haemophilus influenzae type b disease in Canada with exclusive use of a diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b pediatric combination vaccine and an adolescent-adult tetanus-diphtheria-acellular pertussis vaccine: implications for disease prevention in the United States.

BACKGROUND: During the decade 1998-2007, a combination DTaP(5)-IPV/Hib vaccine was used exclusively in Canada to immunize infants and young children against diphtheria, tetanus, pertussis, polio, and invasive Haemophilus influenzae type b (Hib) disease. METHODS: Medline was used to search for publications during 1996-2008 related to the epidemiology and vaccine prevention of pertussis and invasive Hib disease in Canada. Related abstracts and presentations were reviewed, when available, and epidemiologic data since 1985 were obtained from the Public Health Agency of Canada public Web site. RESULTS: Reports of pertussis have declined substantially in preschool and school-aged children during the past decade, and cyclical peaks in disease incidence have been blunted or eliminated. In provinces and territories where Tdap(5) vaccine has been administered to 14- to 16-year-olds, marked reductions of pertussis have been documented in adolescents as well as younger age groups, possibly due to herd immunity. Incidence rates of invasive Hib disease among Canadian children <5 years declined markedly after introduction of Hib conjugate vaccines, and the disease has remained under control with exclusive use of DTaP(5)-IPV/Hib vaccine. Most cases of invasive Hib disease occur among unimmunized or only partially vaccinated children. The reduction of Hib case reports has been documented throughout Canada, including among Aboriginal children who are at high risk for this disease. CONCLUSIONS: The Canadian experience with DTaP(5)-IPV/Hib and Tdap(5) vaccines is relevant to the United States because immunization schedules, vaccination coverage rates, and epidemiologic patterns of pertussis and Hib diseases are similar in the 2 countries, and because both vaccines are licensed for use in the United States.

Persistence of bactericidal antibodies 4 years after a booster dose of quadrivalent meningococcal diphtheria toxoid conjugate vaccine (MenACWY-D).

One dose of quadrivalent meningococcal conjugate vaccine (MenACWY) was first recommended for US adolescents (ages 11-12 years) in 2005 to protect against invasive meningococcal disease (IMD). In 2010, after evidence emerged about waning protection within 5 years after MenACWY vaccination, the US Advisory Committee on Immunization Practices (ACIP) recommended a MenACWY booster at age 16 years. We used a serum bactericidal assay with human complement (hSBA) to evaluate antibody persistence after a MenACWY-D booster in a sample of 110 participants who received the booster 4 years earlier in a phase 2 study. High proportions (89.9-98.2%) of participants maintained hSBA titers (≥1:4) associated with protection against IMD; a majority (81.7-97.2%) also had hSBA titers ≥1:8, a more conservative threshold. These findings support ACIP recommendations regarding MenACWY booster vaccination, which are aimed at protecting adolescents and young adults throughout the period in which they are at increased risk of IMD.

Randomized study of immune responses to two Tdap vaccines among adolescents primed with DTaP and comparison with results among adolescents primed with DTwP.

BACKGROUND: It has been reported that persons primed with acellular (DTaP) pertussis vaccines have reduced duration of pertussis protection compared with those primed with whole-cell (DTwP) vaccines. However, due to the rapid transition to acellular vaccines, studies attempting directly to compare protection among DTaP-primed vs DTwP-primed individuals are subject to confounding by age and other limitations of ecological studies. Using validated assay results and stored sera from multiple Tdap studies, we evaluated two licensed Tdap vaccines among DTaP-primed adolescents to allow comparison with results obtained in the same laboratory from earlier studies involving DTwP-primed adolescents. METHODS: Participants 11-12 years of age who had received exactly 5 doses of DTaP vaccine prior to 7 years of age were randomly assigned in 2012 to receive one of two licensed Tdap vaccines. Serum specimens obtained pre- and post-vaccination were assayed for responses to the vaccines. Current results were then compared to results obtained in the same laboratory from prior randomized Tdap studies conducted among adolescents primed with DTwP or DTaP. RESULTS: Both Tdap vaccines produced strong antibody responses to diphtheria and tetanus; responses to contained pertussis antigens were consistent with the differing levels of those antigens in each Tdap vaccine. However, postvaccination pertussis antibody responses were as much as 71% lower in these DTaP-primed adolescents compared with responses among DTwP-primed adolescents in a prior study of the same two Tdap vaccines. In contrast, results from the present study were similar to those seen in another study of Tdap among DTaP-primed adolescents. DISCUSSION: Taken together, these results from randomized clinical trials provide direct evidence of reduced antibody responses to both licensed Tdap vaccines among adolescents primed with DTaP vaccine, compared with adolescents primed with DTwP vaccine. Clinical trial registry number: ClinicalTrials.gov, NCT01629589.

Randomized Controlled Trial of the Safety and Immunogenicity of Revaccination With Tetanus-Diphtheria-Acellular Pertussis Vaccine (Tdap) in Adults 10 Years After a Previous Dose.

BACKGROUND: Reduced-antigen-content tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in many countries for boosting immunity in adolescents and adults. Although immunity to these antigens wanes with time, currently available Tdap products are not labeled for repeat administration in the United States. METHODS: We performed an observer-blinded, randomized controlled trial in 1330 adults aged 18 to <65 years who received either the Tdap (n = 1002) or tetanus-diphtheria (Td) (n = 328) vaccine 8 to 12 years after a dose of Tdap vaccine administered previously. Solicited adverse events following immunization were documented for 7 days after vaccination, and serious adverse events and adverse events of medical significance were documented for 6 months after vaccination. Levels of antibodies against component vaccine antigens were measured before and 1 month after vaccination. RESULTS: A solicited adverse event was reported by 87.7% of Tdap and 88.0% of Td vaccine recipients. We found no significant differences in the rates of injection-site reactions, systemic reactions, or serious adverse events between the vaccine groups. A robust antibody response to each pertussis antigen in the Tdap-vaccinated group was found; postvaccination-to-prevaccination geometric mean antibody concentration ratios were 8:1 (pertussis toxoid), 5.9 (filamentous hemagglutinin), 6.4 (pertactin), and 5.2 (fimbriae 2 and 3). Postvaccination geometric mean concentrations of tetanus antibody (4.20 and 4.74 IU/mL, respectively) and diphtheria antibody (10.1 and 12.6 IU/mL, respectively) were similar in the Tdap and Td groups, and the rates of seroprotection against tetanus and diphtheria were >99% in both groups. CONCLUSIONS: A second dose of Tdap vaccine in adults approximately 10 years after a previous dose was well tolerated and immunogenic. These data might facilitate consideration of providing Tdap booster doses to adults.

Safety and Immunogenicity of a Full-dose, Split-virion, Inactivated, Quadrivalent Influenza Vaccine in Healthy Children 6-35 Months of Age: A Randomized Controlled Clinical Trial.

BACKGROUND: For children <3 years of age, a half dose of inactivated influenza vaccine (7.5 µg hemagglutinin per strain) has been used for more than 30 years, but several studies indicate that a full dose (15 µg hemagglutinin per strain) can be used in this population without increasing the rate of fever or other reactions. Here, we compare the safety and immunogenicity of full and half doses of quadrivalent, split-virion, inactivated influenza vaccine (IIV4) in children 6-35 months of age. METHODS: In this phase IV, randomized, observer-blinded, multi-center study, healthy children 6-35 months of age were randomized 1:1 to be vaccinated with a half or full dose of IIV4 (NCT02915302). The primary objective was to demonstrate that the rate of any fever (≥38.0°C) up to 7 days after a full dose of IIV4 was noninferior to the rate of fever after a half dose. RESULTS: The study included 1950 children. Noninferiority in the rate of fever was demonstrated for the full dose versus the half dose of IIV4 (difference in rate = 0.84%; 95% confidence interval, -2.13% to 3.80%). Solicited reactions and unsolicited adverse events were similar between the dose groups. No vaccine-related serious adverse events were reported. Noninferiority of both hemagglutination inhibition geometric mean titers and seroconversion rates was demonstrated for all 4 vaccine strains for the full dose versus the half dose. CONCLUSIONS: In children 6-35 months of age, a full dose of IIV4 was immunogenic and had a safety profile comparable to that of a half dose, with no new safety concerns observed.

Analysis of relative effectiveness of high-dose versus standard-dose influenza vaccines using an instrumental variable method.

BACKGROUND: Observational studies of the relative effectiveness of influenza vaccines are essential for public health decision making. Their estimates, however, are subject to bias due to unmeasured confounders. Instrumental variable (IV) methods can control for observed and unobserved confounders. METHODS: We used linked electronic medical record databases in the Veterans Health Administration (VHA) as well as Medicare administrative files to examine the relative vaccine effectiveness (rVE) of high-dose influenza vaccine (HD) versus standard-dose influenza vaccines (SD) in preventing hospitalizations among VHA-enrolled Veterans ≥65 years of age during 5 influenza seasons (2010-2011 through 2014-2015). Using multivariable IV Poisson regression modeling to address unmeasured confounding and bias, we analyzed the data by each season and through longitudinal analysis of all five seasons. FINDINGS: We included 3,638,924 person-influenza seasons of observation where 158,636 (4%) were among HD vaccine recipients and 3,480,288 (96%) were among SD vaccine recipients. Of the 1,728,562 Veterans, 1,702,824 (98.5%) were male and 1,299,412 (75%) were non-Hispanic white. Based on the longitudinal analysis of all five seasons, the IV-adjusted rVE estimate of HD vs. SD was 10% (95% CI, 8-12%) against all-cause hospitalization; 18% (95% CI, 15-21%) against cardiorespiratory-associated hospitalization; and 14% (95% CI, 6-22%) against influenza/pneumonia-associated hospitalization. The findings by season were similar. INTERPRETATION: Our analysis of VHA clinical data collected from approximately 1.7 million Veterans 65 years and older during five seasons demonstrates that high-dose influenza vaccine is more effective than standard-dose influenza vaccines in preventing influenza- or pneumonia-associated hospitalizations, cardiorespiratory hospitalizations, and all-cause hospitalizations.

Efficacy of an acellular pertussis vaccine among adolescents and adults.

BACKGROUND: Pertussis immunization of adults may be necessary to improve the control of a rising burden of disease and infection. This trial of an acellular pertussis vaccine among adolescents and adults evaluated the incidence of pertussis, vaccine safety, immunogenicity, and protective efficacy. METHODS: Bordetella pertussis infections and illnesses were prospectively assessed in 2781 healthy subjects between the ages of 15 and 65 years who were enrolled in a national multicenter, randomized, double-blind trial of an acellular pertussis vaccine. Subjects received either a dose of a tricomponent acellular pertussis vaccine or a hepatitis A vaccine (control) and were monitored for 2.5 years for illnesses with cough that lasted for more than 5 days. Each illness was evaluated with use of a nasopharyngeal aspirate for culture and polymerase-chain-reaction assay, and serum samples from patients in both acute and convalescent stages of illness were analyzed for changes in antibodies to nine B. pertussis antigens. RESULTS: Of the 2781 subjects, 1391 received the acellular pertussis vaccine and 1390 received the control vaccine. The groups had similar ages and demographic characteristics, and the median duration of follow-up was 22 months. The acellular pertussis vaccine was safe and immunogenic. There were 2672 prolonged illnesses with cough, but the incidence of this nonspecific outcome did not vary between the groups, even when stratified according to age, season, and duration of cough. On the basis of the primary pertussis case definition, vaccine protection was 92 percent (95 percent confidence interval, 32 to 99 percent). Among unimmunized controls with illness, 0.7 percent to 5.7 percent had B. pertussis infection, and the percentage increased with the duration of cough. On the basis of other case definitions, the incidence of pertussis in the controls ranged from 370 to 450 cases per 100,000 person-years. CONCLUSIONS: The acellular pertussis vaccine was protective among adolescents and adults, and its routine use might reduce the overall disease burden and transmission to children.

Humoral immunity 10 years after booster immunization with an adolescent and adult formulation combined tetanus, diphtheria, and 5-component acellular pertussis vaccine in the USA.

BACKGROUND: In a prospective, randomized pivotal phase III clinical trial, the immunogenicity and reactogenicity of a tetanus-diphtheria-acellular pertussis vaccine (Tdap) and a tetanus-diphtheria vaccine (Td) vaccine were studied in participants aged 11-64 years. Here we report antibody persistence through 10 years after vaccination. METHODS: Participants who received Tdap or Td in the original phase III trial and provided pre- and post-vaccination serum samples were recruited to donate sera at 1, 3, 5 and 10 years post-vaccination. Antibody concentrations were measured using standard assay techniques. RESULTS: Initially, 1457 Tdap and 1152 Td recipients were included; of these, 175 persons from Tdap group were available at the final study bleed point. Nearly all adolescents in both groups had diphtheria antibody levels ≥0.1 IU/mL 1 month after vaccination, which were maintained in ≥95% of vaccinees at 5 and 10 years. Among adults, ≥94% had diphtheria antibody levels ≥0.1 IU/mL 1 month after vaccination, which were maintained in ≥80% at 5 and 10 years. Nearly all participants had tetanus antibodies ≥0.1 IU/mL throughout the study. PT antibodies declined to pre-vaccination levels approximately 5 years post-vaccination; FHA, PRN and FIM antibodies waned at 5 and 10 years but remained several-fold higher than pre-vaccination levels. CONCLUSIONS: Tdap and Td provide long-lasting protective immune responses against diphtheria and tetanus. Pertussis antibodies following Tdap generally exceeded pre-vaccination levels throughout the study, but showed substantial waning. These data may inform discussion of the need for repeat Tdap booster vaccinations among adults. TRIAL REGISTRATION: The original phase III clinical trial, as well as the 1-, 3-, and 5-year serology follow-up studies were conducted prior to mandatory registration. The 10-year serology follow-up data collection was performed as part of a repeat Tdap administration clinical trial that was registered under clinicaltrials.gov number NCT01439165.

Gastrointestinal Events in High-Dose vs Standard-Dose Influenza Vaccine Recipients.

Passive surveillance data had signaled the possibility of gastrointestinal adverse events occurring after the administration of high-dose inactivated influenza vaccine (IIV-HD). However, in a large, prospective randomized clinical trial, rates of serious gastrointestinal events were no greater among IIV-HD recipients than among those who received a standard-dose influenza vaccine.