Seasonal Trivalent Influenza Vaccine Research Articles

Safe administration of the seasonal trivalent influenza vaccine to children with severe egg allergy

BackgroundAnaphylaxis to egg or severe egg allergy has been considered a contraindication to receiving trivalent seasonal influenza vaccine (TIV). ObjectiveTo evaluate the safety of TIV among severely egg allergic children. MethodsA 2-phase, multicenter study at 7 sites was conducted between October 2010 and March 2012. Inclusion criteria included a history of a severe reaction, including anaphylaxis, to the ingestion of egg and a positive skin test result or evidence of serum specific IgE antibody to egg. Phase 1 consisted of a randomized, prospective, double-blind, placebo controlled trial of TIV administration to egg allergic children, using a 2-step approach; group A received 0.1 mL of influenza vaccine, followed in 30 minutes if no reaction with the remainder of an age-appropriate dose, whereas group B received an injection of normal saline followed in 30 minutes if no reaction with the full 100% of the age-appropriate dose. Phase 2 was a retrospective analysis of single dose vs split-dose administration of TIV in eligible study participants who declined participation in the randomized controlled trial. ResultsThirty-one study participants were prospectively evaluated in the randomized controlled trial (group A, 14; group B, 17); 45.1% had a history of anaphylaxis after egg ingestion. A total of 112 participants were retrospectively evaluated (87 with the single dose and 25 with the split dose); 77.6% of participants had a history of anaphylaxis after egg ingestion. All participants in both phases received TIV without developing an allergic reaction. ConclusionTIV administration is safe even in children with histories of severe egg allergy. Use of 2-step split dosing appears unnecessary because a single dose was well tolerated.

Cross-reactive and Vaccine-Induced Antibody to an Emerging Swine-Origin Variant of Influenza A Virus Subtype H3N2 (H3N2v)

Cases of infection due to a novel swine-origin variant of influenza A virus subtype H3N2 (H3N2v) have recently been identified in the United States, primarily among children. We estimate levels of cross-reactive antibody to H3N2v by age and assess whether seasonal trivalent inactivated influenza vaccine (TIV), with or without adjuvant, may increase seroprotection. Antibody to H3N2v was assessed by hemagglutination inhibition (HI) assay and, for a subset, also by microneutralization assay. Seroprevalence and seroprotection were defined as an HI titer of ≥40, and levels were compared with those for ancestral and contemporary human strains. The analysis included 1116 sera collected during fall 2010, corresponding to approximately 100 sera per decade of life. Vaccine-induced antibody levels were also assessed in sera from 136 children aged <10 years and 65 adults aged 20-59 years before and after receipt of 2010-2011 split TIV and in sera from 182 elderly individuals aged ≥65 years before and after receipt of 2011-2012 split TIV (for 31 individuals), MF59-adjuvanted TIV (for 72), or unadjuvanted subunit TIV (for 79). The overall prevalence of HI titers of ≥40 against A(H3N2)v was 25%. No children aged <5 years and <20% of individuals aged ≤14 years or ≥40 years had an HI titer of ≥40. Conversely, among individuals aged 15-39 years, half of teens and adults showed H3N2v seroprotection. Following TIV receipt, <15% of individuals in any vaccine group developed a 4-fold increase in antibody level. A substantial proportion of adolescents and young adults have cross-reactive antibody against emerging H3N2v, whereas children and older adults show broad susceptibility. Recent formulations of TIV do not substantially increase seroprotection. A specific vaccine would be needed if H3N2v establishes epidemic spread. NCT01140009 and NCT01368796.

Recommendations for Prevention and Control of Influenza in Children, 2012–2013

The purpose of this statement is to update recommendations for routine use of trivalent seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children. The key points for the upcoming 2012-2013 season are: (1) this year's trivalent influenza vaccine contains A/California/7/2009 (H1N1)-like antigen (derived from influenza A [H1N1] pdm09 [pH1N1] virus); A/Victoria/361/2011 (H3N2)-like antigen; and B/Wisconsin/1/2010-like antigen (the influenza A [H3N2] and B antigens differ from those contained in the 2010-2011 and 2011-2012 seasonal vaccines); (2) annual universal influenza immunization is indicated; and (3) an updated dosing algorithm for administration of influenza vaccine to children 6 months through 8 years of age has been created. Pediatricians, nurses, and all health care personnel should promote influenza vaccine use and infection control measures. In addition, pediatricians should promptly identify influenza infections to enable rapid treatment, when indicated, to reduce morbidity and mortality.

Egg-allergic patients can be safely vaccinated against influenza

As the influenza vaccine contains residual egg protein, its administration to egg-allergic patients had always raised theoretical concerns about anaphylaxis.1 We report our experience with the vaccination of egg-allergic patients with a trivalent inactivated seasonal influenza vaccine administered during 5 seasons (2007-2011) and summarize the current published clinical experience with these patients.

A(H1N1)pdm09 Vaccination of Health Care Workers: Improved Immune Responses in Low Responders Following Revaccination

We conducted a clinical trial in October 2009 to evaluate the immunogenicity of the AS03-adjuvanted influenza vaccine (pH1N1 vaccine) in health care workers (HCWs). By 2 weeks after vaccination, 97% had protective hemagglutinin inhibition (HI) titers (≥ 40) however, 16% were low responders (LR) and failed to maintain a protective response 90 days after vaccination. We analyzed the humoral responses (HI, antibody-secreting cell [ASC], and serum immunoglobulin G [IgG]) in 15 LRs and 25 control HCWs. Twelve LRs were revaccinated with the pH1N1 vaccine, and 7 were subsequently vaccinated with the 2010 seasonal trivalent influenza vaccine. We conducted a long-term analysis of the humoral and CD4(+) T-helper (Th) 1 responses. The LRs had a slower HI antibody response than the control HCWs, with protective antibody titers not reached until 2 weeks after vaccination in the majority of the participants. The LRs also had significantly lower IgG ASCs at day 7 and HA1-specific serum IgG responses at day 21, compared with the control HCWs. Revaccination with the pH1N1 vaccine elicited rapid HI antibody, ASC, memory B cell, and multifunctional CD4(+) Th1 cell responses. This study shows that revaccination of low-responding HCWs with the pH1N1 vaccine is required for maintaining long-term protection. NCT01003288.

Effect of Influenza Vaccination in the First Trimester of Pregnancy

To estimate the effect of first-trimester influenza vaccination on fetal and neonatal outcomes. This was a retrospective cohort study examining delivery and neonatal outcomes after antepartum exposure to the seasonal trivalent inactive influenza vaccine. Data were collected and entered into an established computerized database. Outcomes by trimester of vaccination were then compared with women who did not receive the vaccine. During the 5-year study period, 10,225 women received the seasonal influenza vaccine antepartum; 8,690 of these delivered at our institution, 439 in the first trimester and 8,251 in the second and third trimesters. Women vaccinated antepartum were significantly older with higher parity than women who declined vaccination. Neonates born to mothers receiving the vaccine in any trimester did not have an increase in major malformations regardless of trimester of vaccination (2% regardless of vaccination group, P=.9). Stillbirth (0.3% compared with 0.6%, P=.006), neonatal death (0.2% compared with 0.4%, P=.01), and premature delivery (5% compared with 6%, P=.004) were significantly decreased in the vaccinated group. Influenza vaccination in the first trimester was not associated with an increase in major malformation rates and was associated with a decrease in the overall stillbirth rate. This information will aid in counseling women regarding the safety of influenza vaccination in the first trimester.

Humoral Antibody Response After Receipt of Inactivated Seasonal Influenza Vaccinations One Year Apart in Children

Annual vaccination against seasonal influenza viruses is recommended for school-age children in some countries. There are limited data on the immunogenicity and efficacy of repeated influenza vaccinations. In a randomized controlled trial, we administered seasonal trivalent inactivated influenza vaccine (TIV) or placebo to 64 children 6-15 years of age in two consecutive years and explored their humoral antibody responses. Receipt of TIV in the first year was associated with lower antibody titer rises in the second year to seasonal influenza A(H1N1) and A(H3N2) strains for which the vaccine strains remained unchanged. Antibody response to a different influenza B strain in the second year was unaffected by receipt of TIV in the first year. Children who received TIV in both years showed higher antibody titers against pandemic A(H1N1) which was not included in either TIV. Results from our study suggest that humoral antibody response to TIV may be lower in children receiving repeated vaccination, but receipt of TIV induced seroprotection in most subjects. Our study was underpowered to explore whether differences in immunogenicity translated to differences in vaccine efficacy.

Antibody responses against influenza A(H1N1)pdm09 virus after sequential vaccination with pandemic and seasonal influenza vaccines in Finnish healthcare professionals

Background Influenza A(H1N1)pdm09 virus has been circulating in human population for three epidemic seasons. During this time, monovalent pandemic and trivalent seasonal influenza vaccination against this virus have been offered to Finnish healthcare professionals. It is, however, unclear how well vaccine‐induced antibodies recognize different strains of influenza A(H1N1)pdm09 circulating in the population and whether the booster vaccination with seasonal influenza vaccine would broaden the antibody cross‐reactivity. Objectives Influenza vaccine‐induced humoral immunity against several isolates of influenza A(H1N1)pdm09 virus was analyzed in healthcare professionals. Age‐dependent responses were also analyzed. Methods Influenza viruses were selected to represent viruses that circulated in Finland during two consecutive influenza epidemic seasons 2009–2010 and 2010–2011. Serum samples from vaccinated volunteers, age 20–64 years, were collected before and after vaccination with AS03‐adjuvanted pandemic and non‐adjuvanted trivalent seasonal influenza vaccine that was given 1 year later. Results Single dose of pandemic vaccine induced a good albeit variable antibody response. On day 21 after vaccination, depending on the virus strain, 14–75% of vaccinated had reached antibody titers (≥1:40) considered seroprotective. The booster vaccination 1 year later with a seasonal vaccine elevated the seroprotection rate to 57–98%. After primary immunization, younger individuals (20–48 years) had significantly higher antibody titers against all tested viruses than older persons (49–64 years) but this difference disappeared after the seasonal booster vaccination. Conclusions Even a few amino acid changes in influenza A HA may compromise the vaccine‐induced antibody recognition. Older adults (49 years and older) may benefit more from repeated influenza vaccinations.

A randomized control trial comparing immunogenicity, safety, and preference for self- versus nurse-administered intradermal influenza vaccine

BackgroundIntradermally administered influenza vaccine is as immunogenic as intramuscular vaccine at a lower unit dose. New microinjection systems could allow self-administration of vaccine, potentially reducing the cost and inconvenience. ObjectiveTo compare the immunogenicity, reactogenicity, success rate, and acceptability of self- versus nurse-administered intradermal trivalent seasonal influenza vaccine. MethodsAdults (18–59years old) were randomized to either self- or nurse-administered intradermal vaccine. Prior to vaccination, participants completed a questionnaire and had blood drawn for hemagglutination inhibition titres. Participants in the nurse-administered group were vaccinated by study personnel. The self-administered group were given an instruction sheet and administered their own vaccine. All participants completed a questionnaire and adverse event diaries for 21days post vaccination, at which time blood was again collected. ResultsOf the 228 participants, 115 were randomized to self-administration and 113 to nurse administration. Groups did not differ by sex, age, or levels of seroprotection at baseline. Of the 114 who completed self-administration, 106 (93%) were successful on the first attempt. There were no group differences in measures of immunogenicity for any of the strains. Self-administering participants reported a lower mean pain rating at vaccination but had larger areas of redness post-vaccination. Seventy percent of all participants said they would prefer intradermal over intramuscular vaccinations in the future, if given the choice. ConclusionCompared to nurse-administered intradermal influenza vaccine, self-administered vaccine was immunologically non-inferior and reached all EMA immunogenicity criteria for the A strains, was highly successful and well-accepted by study participants. Together, these data provide preliminary evidence of feasibility for this method of influenza vaccine administration, which may improve vaccine uptake in adults and increase efficiency of vaccine delivery during outbreaks.

Safety and immunogenicity of an AS03-adjuvanted A(H1N1)pmd09 vaccine administered simultaneously or sequentially with a seasonal trivalent vaccine in adults 61 years or older: Data from two multicentre randomised trials

During the 2009–2010 Northern Hemisphere influenza season, both seasonal and pandemic influenza vaccines were expected to be administered to elderly people, which is an important target group for influenza vaccination. Two multicentre randomised clinical studies were conducted in participants aged ≥61 years to assess the immunogenicity and reactogenicity following vaccination with two doses of an AS03-adjuvanted A(H1N1)pmd09 vaccine when either sequentially administered (21 days before first dose [N=73] or 21 days after second dose [N=72]) or co-administered (first dose [N=84] or second dose [N=84]) with a licensed trivalent seasonal influenza vaccine (TIV). Overall, 313 participants from 2 centres in Sweden (ClinicalTrials.gov, NCT00968890) and 6 centres in Germany (NCT00971425) were randomised to one of the four treatment groups. The AS03-adjuvanted A(H1N1)pmd09 vaccine elicited a good immune response against A(H1N1)pmd09-like virus in all treatment groups after the first and second dose, meeting and exceeding the European licensing criteria for pandemic influenza vaccines. After one dose of the AS03-adjuvanted A(H1N1)pmd09 vaccine, haemagglutination inhibition seroconversion rates ranged from 85% (95% confidence interval: 74–93%) to 93% (85–97%), seroprotection rates from 87% (76–94%) to 96% (90–99%) and geometric mean fold rise from 15 (11–19) to 20 (16–25). The haemagglutination inhibition immune responses to the AS03-adjuvanted A(H1N1)pmd09 vaccine seemed lower when TIV was administered 3 weeks before, while immune responses to TIV seemed not affected by either vaccination schedule. Solicited symptoms were more frequently reported following administration of the AS03-adjuvanted A(H1N1)pmd09 vaccine compared to TIV, but these were mainly mild to moderate in intensity and transient in the four treatment groups. These results suggest that sequential or co-administration of the AS03-adjuvanted A(H1N1)pmd09 vaccine and TIV induced a good immune response to both vaccines and had a clinically acceptable safety profile in people aged ≥61 years.

Immunogenicity of a Monovalent Pandemic Influenza A H1N1 Virus Vaccine with or without Prior Seasonal Influenza Vaccine Administration

The immunogenicity of pandemic influenza A H1N1 virus (A/H1pdm) vaccine might be modified by prior seasonal trivalent influenza vaccine (sTIV) administration. We conducted a retrospective analysis of immunogenicity of 243 health care workers (number of sTIV-positive [sTIV(+)] subjects, 216; number of sTIV(-) subjects, 27) by hemagglutination inhibition. There was no significant difference in the ratios of antibody titers of ≥40 (41.2% versus 48.1%; P = 0.49) and fold increases in geometric mean titer (3.8 versus 4.5; P = 0.37). sTIV injected 7 to 10 days prior to A/H1pdm vaccine administration did not interfere with the immunogenicity of the latter.

A non-adjuvanted whole-virus H1N1 pandemic vaccine is well tolerated and highly immunogenic in children and adolescents and induces substantial immunological memory

This phase 1/2 open-label, randomized clinical study investigated the safety and immunogenicity of a non-adjuvanted, whole virus, Vero cell-derived H1N1 pandemic influenza vaccine (A/H1N1/California/07/2009) in children and adolescents (6 months to 17 years). Subjects were stratified by age (6–11 months, 12–35 months, 3–8 years, 9–17 years) to receive two vaccinations 21 days apart of either the 3.75μg or 7.5μg dose. A booster with a licensed trivalent seasonal (2010/2011) influenza vaccine was administered one year after the first vaccination to a subgroup that had previously received the 7.5μg dose.A single vaccination with the 7.5μg dose induced high seroprotection rates in all subjects, namely: 88.0% (9–17 years); 68.0% (3–8 years); 42.9% (12–35 months); and 50.0% (6–11 months). Following a second vaccination, seroprotection rates ranged from 84.2% to 100%. GMTs after two vaccinations with the 7.5μg dose (as determined by HI) were also substantial: reaching 210.0 (9–17 years), 196.2 (3–8 years), 118.9 (12–35 months) and 99.6 (6–11 months). Antibody persistence was demonstrated at 6 months (GMTs ranging from 65.6 to 212.8 with the 7.5μg dose) and at 12 months (GMTs ranging from 33.6 to 124.1 with the 7.5μg dose) after primary vaccination. The booster vaccination induced a strong response to the A/California/07/2009 strain, reaching 100% seroprotection in all age groups, with GMTs ranging from 640.0 to 886.3.The vaccine was well tolerated, inducing low adverse reaction rates (overall fever rate: 6% after the first vaccination; 7% after the second vaccination), even in young children. These data confirm that the H1N1 whole-virus Vero cell-derived pandemic influenza vaccine is suitable for use in children and adolescents; a 2-dose primary vaccination induces a memory response in a naïve population that can be effectively boosted with the A/H1N1/California/07/2009 component of a seasonal influenza vaccine. ClinicalTrials.gov Identifier: NCT00976469.

Safety and Immune Responses in Children After Concurrent or Sequential 2009 H1N1 and 2009-2010 Seasonal Trivalent Influenza Vaccinations

Administering 2 separate vaccines for seasonal and pandemic influenza was necessary in 2009. Therefore, we conducted a randomized trial of monovalent 2009 H1N1 influenza vaccine (2009 H1N1 vaccine) and seasonal trivalent inactivated influenza vaccine (TIV; split virion) given sequentially or concurrently in previously vaccinated children. Children randomized to 4 study groups and stratified by age received 1 dose of seasonal TIV and 2 doses of 2009 H1N1 vaccine in 1 of 4 combinations. Injections were given at 21-day intervals and serum samples for hemagglutination inhibition antibody responses were obtained prior to and 21 days after each vaccination. Reactogenicity and adverse events were monitored. All combinations of vaccines were safe in the 531 children enrolled. Generally, 1 dose of 2009 H1N1 vaccine and 1 dose of TIV, regardless of sequence or concurrency of administration, was immunogenic in children ≥ 10 years of age; children <10 years of age required 2 doses of 2009 H1N1 vaccine. Vaccines were generally well tolerated. The immune responses to 2009 H1N1 vaccine were adequate regardless of the sequence of vaccination in all age groups but the sequence affected titers to TIV antigens. Two doses of 2009 H1N1 vaccine were required to achieve a protective immune response in children <10 years of age. NCT00943202.

Short and Long-Term Safety of the 2009 AS03-Adjuvanted Pandemic Vaccine

BackgroundThis study assessed the short and the long term safety of the 2009 AS03 adjuvanted monovalent pandemic vaccine through an active web-based electronic surveillance. We compared its safety profile to that of the seasonal trivalent inactivated influenza vaccine (TIV) for 2010–2011.Methodology/Principal FindingsHealth care workers (HCW) vaccinated in 2009 with the pandemic vaccine (Arepanrix ® from GSK) or HCW vaccinated in 2010 with the 2010–2011 TIV were invited to participate in a web-based active surveillance of vaccine safety. They completed two surveys the day-8 survey covered the first 7 days post-vaccination and the day-29 survey covered events occurring 8 to 28 days after vaccination. Those who reported a problem were called by a nurse to obtain details. The main outcome was the occurrence of a new health problem or the worsening of an existing health condition that resulted in a medical consultation or work absenteeism. For the pandemic vaccine, a six-month follow-up for the occurrence of serious adverse events (SAE) was conducted. Among the 6242 HCW who received the pandemic vaccine, 440 (7%) reported 468 events compared to 328 of the 7645 HCW (4.3%) who reported 339 events after the seasonal vaccine. The 2009 pandemic vaccine was associated with significantly more local reactions than the 2010–2011 seasonal vaccine (1% vs. 0.03%, p<0.001). Paresthesia was reported by 7 HCW (0.1%) after the pandemic vaccine but by none after the seasonal vaccine. For the pandemic vaccine, no clustering of SAE was found in the 6 month follow-up.ConclusionThe 2009 pandemic vaccine seems to have a good safety profile, similar to the 2010–2011 TIV, with the exception of local reactions. This surveillance was adequately powered to identify AE associated with an excess risk ≥1 per 1000 vaccinations but is insufficient to detect rare AE.Trial RegistrationClinicalTrials.gov NCT01289418, NCT01318876

Mycophenolate and lower graft function reduce the seroresponse of kidney transplant recipients to pandemic H1N1 vaccination

In late 2009 transplant organizations recommended that kidney recipients be vaccinated for pandemic H1N1 influenza (pH1N1); however, the vaccine efficacy was unknown. We had offered a monovalent non-adjuvanted pH1N1 vaccine to transplant recipients. Here we compared the pre- and post-vaccination seroresponses of 151 transplant recipients to that of 71 hemodialysis patients and 30 healthy controls. Baseline seroprotection was similar between groups but was significantly different at 1 month (44, 56, and 87%, respectively). Seroconversion was significantly less common for transplant recipients (32%) than dialysis patients (45%) and healthy controls (77%). After adjusting for age and gender, dialysis patients were significantly more likely (2.7-fold) to achieve new seroprotection than transplant recipients. The likelihood of seroprotection in transplant recipients was significantly reduced by mycophenolate use (adjusted odds ratio 0.24), in a dose-dependent manner, and by reduced eGFR (adjusted odds ratio 0.16 for worst to best). Seroprotection and geometric mean antibody titers increased substantially in 49 transplant recipients who subsequently received the 2010 seasonal influenza vaccine. Thus, patients requiring renal replacement therapy had reduced seroresponses to vaccination with the monovalent vaccine compared with healthy controls. Transplant recipient responses were further reduced if they were receiving mycophenolate or had significantly lower graft function.

Prevention of Mortality and Pneumonia Among Nursing Home Older Adults by Dual Pneumococcal and Seasonal Influenza Vaccination During a Pandemic Caused by Novel Pandemic Influenza A (H1N1)

To evaluate the efficacy of dual vaccination of seasonal influenza and pneumococcus in nursing home older adults during a novel pandemic of influenza A (H1N1). Nine nursing homes in Hong Kong. A total of 532 nursing home older adults were included in the study. Efficacy of dual vaccination of seasonal influenza and pneumococcus in nursing home older adults during a novel pandemic influenza A (H1N1). A prospective 12-month cohort study was conducted on older residents from December 2009 to November 2010. Participants were divided into 3 groups according to their choice of vaccination: received both seasonal influenza and 23-valent pneumococcal polysaccharide vaccine (PPV-TIV group), received seasonal influenza vaccine alone (TIV group), and those who refused both vaccinations (unvaccinated group). Those who had received vaccination for influenza A (H1N1) were excluded. Outcome measures included mortality from all causes, pneumonia, and vascular causes. There were 246 in the PPV-TIV group, 211 in the TIV group, and 75 in the unvaccinated group. Baseline characteristics were similar among the groups. The 12-month mortality rates of the PPV-TIV, TIV alone group, and unvaccinated group were 17.1%, 27.0%, and 37.3% respectively (P < .001). Multivariate analysis demonstrated that, compared with vaccination of seasonal influenza alone, dual vaccination significantly reduced all-cause mortality (hazard ratio [HR] 0.54; 95% confidence interval [CI]: 0.35-0.84; P < .01), mortality from pneumonia (HR 0.60; 95% CI: 0.35-0.99; P < .05), and mortality from vascular causes (HR 0.24; 95% CI: 0.09-0.64; P < .01). During an influenza pandemic or when the circulating influenza strain was not matched by the trivalent seasonal influenza vaccine, dual vaccination of influenza and pneumococcus provided additional protection to nursing home older adults in reducing mortality.

Design and initiation of a study to assess the direct and indirect effects of influenza vaccine given to children in rural India

The burden of disease due to influenza is not well characterized for children in developing countries and the effectiveness of available influenza vaccines in lower resource settings has not been established. We initiated a prospective, longitudinal, phase IV, household-randomized, controlled, observer-blinded three year study (2009–2011) in a rural community of India to measure the total and indirect household protective effects of immunizing children ages 6 months through 10 years with seasonal inactivated trivalent influenza vaccine (TIV) or a control vaccine (n=3697). Active weekly surveillance was conducted year round with home visits for identification of febrile acute respiratory illness (FARI) conducted for all vaccine recipients and household members (n=18,220). Nasal and throat swabs were collected from each FARI episode for influenza detection by real-time reverse transcription polymerase chain reaction. The primary outcome was reduction in laboratory confirmed influenza infections in the influenza vaccine versus control vaccine group, with secondary outcome assessing indirect effects among the entire study population. This report describes the study site, cluster study design, choice of study and control vaccines, and the initial enrollment in the study.

Age-specific vaccine effectiveness of seasonal 2010/2011 and pandemic influenza A(H1N1) 2009 vaccines in preventing influenza in the United Kingdom.

An analysis was undertaken to measure age-specific vaccine effectiveness (VE) of 2010/11 trivalent seasonal influenza vaccine (TIV) and monovalent 2009 pandemic influenza vaccine (PIV) administered in 2009/2010. The test-negative case-control study design was employed based on patients consulting primary care. Overall TIV effectiveness, adjusted for age and month, against confirmed influenza A(H1N1)pdm 2009 infection was 56% (95% CI 42-66); age-specific adjusted VE was 87% (95% CI 45-97) in <5-year-olds and 84% (95% CI 27-97) in 5- to 14-year-olds. Adjusted VE for PIV was only 28% (95% CI -6 to 51) overall and 72% (95% CI 15-91) in <5-year-olds. For confirmed influenza B infection, TIV effectiveness was 57% (95% CI 42-68) and in 5- to 14-year-olds 75% (95% CI 32-91). TIV provided moderate protection against the main circulating strains in 2010/2011, with higher protection in children. PIV administered during the previous season provided residual protection after 1 year, particularly in the <5 years age group.

Protective Efficacy Against Pandemic Influenza of Seasonal Influenza Vaccination in Children in Hong Kong: A Randomized Controlled Trial

The efficacy of seasonal influenza vaccination against 2009 pandemic influenza A(H1N1) remains unclear. One child aged 6-17 years in each of 796 households was randomized to receive 2009-2010 seasonal trivalent inactivated influenza vaccine (TIV) or saline placebo between August 2009 and February 2010. Households were followed up with serology, symptom diaries, and collection of respiratory specimens during illnesses. The primary outcomes were influenza infection confirmed by reverse-transcription polymerase chain reaction (RT-PCR) or a ≥4-fold rise in serum antibody titer measured by hemagglutination inhibition assay. Receipt of TIV led to 8-13-fold mean geometric rises in antibody titers against seasonal A and B viruses, but only 1.5-fold mean geometric rises against the pandemic A(H1N1) virus that was not included in the vaccine. Children who received TIV had a reduced risk of seasonal influenza B confirmed by RT-PCR, with a vaccine efficacy estimate of 66% (95% confidence interval [CI], 31%-83%). Children who received TIV also a had reduced risk of pandemic influenza A(H1N1) indicated by serology, with a vaccine efficacy estimate of 47% (95% CI, 15%-67%). Seasonal TIV prevented pandemic influenza A(H1N1) and influenza B infections in children. Pandemic A(H1N1) circulated at the time of vaccination and for a short time afterward with no substantial seasonal influenza activity during that period. The potential mechanism for seasonal TIV to provide protection, possibly short lived, for children against pandemic A(H1N1) infection despite poor cross-reactive serologic response deserves further investigation. Clinical Trials Registration. NCT00792051.

A Randomized, Controlled Trial in Children to Assess the Immunogenicity and Safety of a Thimerosal-free Trivalent Seasonal Influenza Vaccine

Children are at high risk of acquiring and transmitting influenza infection and are a high priority group for influenza vaccination. This was a randomized, observer-blind, multicenter study (NCT00980005) based in the United States. Children were randomized (1:1) to receive either the study vaccine, a thimerosal-free trivalent inactivated influenza vaccine or an active comparator (control vaccine) and were allotted to 1 of 3 age categories: 3-4, 5-8 and 9-17 years. The primary objective was to show noninferiority of the study vaccine versus a US- licensed control influenza vaccine. A total of 2116 children were vaccinated (study vaccine N = 1055, control vaccine N = 1061). The predefined noninferiority criteria and the Center for Biologics Evaluation and Research criteria for clinical benefit were met for all 3 seasonal virus strains in all children and each age strata. The ratios of the adjusted geometric mean titers (control vaccine over study vaccine) ranged from 0.93 to 1.03 for the 3 virus strains whereas the differences in seroconversion rate (control vaccine minus study vaccine) were between -2.42% and -1.60%. Postvaccination geometric mean titers (range: 213.7-414.7 versus 200.2-451.9) and seroconversion rates (range: 59.8-81.1% versus 58.2-78.6%) were comparable for the 2 vaccines. The safety and reactogenicity profiles were similar for both treatment groups in all age strata. Immunologic noninferiority of the study vaccine was demonstrated compared with the control vaccine. Furthermore, the study vaccine had a similar safety profile as the control vaccine in children.