Dose Of Trivalent Influenza Vaccine Research Articles

Effect of Influenza Vaccination on Rate of Influenza Virus Infection in Chinese Military Personnel, 2015-2016: A Cluster Randomized Trial.

Influenza is a major cause of morbidity and mortality. The protective effect of a trivalent influenza vaccine (TIV) is undetermined in military personnel. We conducted an open-label, cluster randomized trial on active-duty servicemen of Beijing, Tianjin, and Shijiazhuang, who were randomly assigned to receive either a single dose of TIV or no treatment, according to cluster randomized sampling. The subjects were then followed for a maximum of six months to assess the incidence of laboratory-confirmed influenza. A total of 5445 subjects in 114 clusters received one dose of TIV before the 2015/2016 influenza season. Laboratory-confirmed influenza was identified in 18 in the vaccine group compared with 87 in the control group (6031 subjects in 114 clusters), resulting in a vaccine effectiveness (VE) of 76.4% (95%CI: 60.7 to 85.8) against laboratory-confirmed influenza. Influenza-like illness was diagnosed in 132 in the vaccine group compared with 420 in the control group, resulting in a VE of 64.1% (95%CI: 56.2 to 70.6). The estimated VE against influenza B viruses was 80.5% (95%CI: 65.6 to 88.9) and 8.6% (95%CI: -241 to 75.5) against influenza A viruses. In conclusion, the trivalent influenza vaccine is moderately effective, highly immunogenic, and generally safe to use in healthy male military servicemen.

Influenza vaccination in breast cancer patients during subcutaneous trastuzumab in adjuvant setting

BackgroundDespite the current recommendation for influenza vaccination in cancer patients with active oncological therapy, limited data are available on the efficacy of vaccination in cancer patients receiving targeted therapies. We aimed to investigate the immunogenicity and tolerability of influenza vaccination in breast cancer patients treated with trastuzumab in adjuvant setting.MethodsA prospective open-label multicenter study was performed including patients with breast cancer during trastuzumab treatment in adjuvant setting and healthy controls. Blood samples were taken before, 4 weeks after, and 12 weeks after a single dose of trivalent influenza vaccine containing inactivated A/California/7/2009 (H1N1) pdm09, A/Hongkong4801/2014 (H3N2), and B/Brisbane/60/2008. Levels of serum antibody titers to hemagglutinin for H1N1 and influenza B strains were measured.ResultsTwenty breast cancer patients and 37 controls were included in the study. No difference in seroprotection rate between trastuzumab-treated patients and controls was observed for either H1N1 (100% in both groups) or B strain (78.9% vs. 89.2%, p value = 0.423). A statistically significant increase in geometric mean titers from baseline was seen in both groups and was evident both 4 weeks and 12 weeks after vaccination. Adverse events in the trastuzumab-treated group were uncommon and mild with only one serious adverse event not related to vaccination.ConclusionBreast cancer patients treated with trastuzumab in adjuvant setting seem to benefit from influenza vaccination in terms of immunogenicity without increasing the risk for adverse events. The current data support the recommendation to offer influenza vaccination in breast cancer patients treated with this type of targeted therapy.

Immune response to influenza vaccination in ESRD patients undergoing hemodialysis vs. hemodiafiltration

BackgroundOn-line hemodiafiltration (HDF) clears more azotemic toxins compared to high-flux hemodialysis (HD). The response to vaccination is impaired in dialysis patients. We wished to determine whether the immune responses to influenza vaccine in dialysis patients treated by HDF were stronger than those treated by HD.Materials and methodsWe conducted a prospective cohort study in chronic dialysis patients during the 2016 and 2017 influenza seasons. All participants received a single standard dose of trivalent influenza vaccine, and we studied the elicited humoral immune response by hemagglutination inhibition test, and cell-mediated immune response by enumeration of lymphocyte cellular markers and proliferation assays.ResultsWe immunized 60 end-stage renal disease (ESRD) patients: 42 (70%) treated with HD and 18 patients (30%) with HDF. The median (interquartile range) age was 65.0 (55.0–74.5) years. All patients developed seroprotection to at least one influenza vaccine strain at one month post-vaccination, and did not differ between groups. By logistic regression, age was the only factor independently associated with seroconversion to all vaccine strains (odds ratio 0.89, 95% confidence interval 0.80–0.98; p = 0.022). Seroprotection to all vaccine strains was sustained for longer in patients treated with HDF, and the results remained the same after age adjustment. For cellular immune response, patients who seroconverted to all vaccine strains had higher CD38+ T cell subpopulations pre-vaccination. Patients treated by HDF had higher lymphocyte proliferation to circulating influenza A strains.ConclusionsSeroconversion to all influenza vaccine strains was associated with age. Patients treated with HDF demonstrated seroprotection was sustained for longer compared to those treated by HD and greater lymphocyte proliferation to circulating influenza A strains. These encouraging results for HDF require confirmation in a larger dialysis population.Trial registrationClinicalTrial.gov, NCT04122222.

Evaluation of Waning Immunity at 6 Months after Both Trivalent and Quadrivalent Influenza Vaccination in Korean Children Aged 6-35 Months.

BackgroundThe titer of influenza vaccine-induced antibodies declines over time, and younger children have lower immunogenicity and shorter duration of immunity. This study aimed to compare persistence of antibody at 6 months after influenza vaccination according to influenza virus strains, vaccine type, antigen dose, and primed status in children aged 6 to 35 months.MethodsA total 124 healthy children aged 6 to 35 months were enrolled from September to December 2016 at 10 hospitals in Korea and randomly assigned to either a full dose of quadrivalent influenza vaccine or a half dose of trivalent influenza vaccine with Victoria B strain group. Hemagglutination inhibition antibody titers (that measure the seroprotection rates) were assessed for the recommended influenza strains at 6 months post vaccination.ResultsThe seroprotection rates at 6 months for strains A (H1N1), A (H3N2), B/Yamagata, and B/Victoria were 88.7%, 97.4%, 36.6%, and 27.6%, respectively. The seroprotection rates for A (H1N1), A (H3N2) and B (Victoria) were 91.4%, 98.7% and 27.5% in a full dose of quadrivalent vaccine vs. 83.7%, 94.6% and 27.9% in a half dose trivalent vaccine, respectively. The seroprotection rate for the B (Yamagata) strain was 23.8% in the quadrivalent group and 14.0% in the trivalent group.ConclusionPersistence of antibodies at 6 months was more favorable against the influenza A strains than against the B strains. Persistence of antibodies to additional B strain at 6 months was superior in the quadrivalent vaccine group. The immunity of primed children with different B strains was not superior to that of the unprimed group with another B strain.

Safety assessment of seasonal trivalent influenza vaccine produced by Instituto Butantan from 2013 to 2017.

ABSTRACTVaccination has been a successful strategy in influenza prevention. However, despite the safety and efficacy of the vaccines, they can cause adverse events following immunization (AEFI). Moreover, due to the vaccination success, most of vaccine-preventable diseases (VPD) have become rare, and public attention has been shifted from VPD to the AEFI associated with vaccination. This manuscript describes the safety of Instituto Butantan (IB) seasonal trivalent influenza vaccine (TIV) from 2013 to 2017. AEFI data were received by the Department of Pharmacovigilance of IB (PV-IB), from January the 1st 2013 to December the 31st 2017, and were recorded in an electronic database (OpenClinica©). PV-IB received 1,415 Individual Case Safety Reports (ICSR) associated with the TIV; 1,253 ICSR with at least one AEFI were analyzed and 4,140 AEFI were identified. The other 162 (11.4%) cases did not present any symptom. Among the total of AEFI, 405 (9.8%) were classified as serious. AEFI with the highest incidence rates per 100,000 doses of TIV were: “local pain” (0.28), “local erythema” (0.23), “local warmth” (0.22), “local swelling” (0.20) and “fever” (0.19). PV-IB received 175 (4.2%) occurrences of SAE of special interest, of which 75 (1.8%) anaphylaxis/anaphylactic reactions, 56 (1.4%) neurological syndromes (including seven Guillain-Barré Syndrome) and 44 (1.1%) convulsion/febrile convulsion. The results of this manuscript suggested that Instituto Butantan trivalent influenza vaccine (IB-TIV) is safe, as most of the reported AEFI were classified as non-serious. AEFI described for the IB-TIV are in agreement with the ones described in the literature for similar vaccines.

Influenza vaccine efficacy in young children attending childcare: A randomised controlled trial.

Influenza causes a substantial burden in young children. Vaccine efficacy (VE) data are limited in this age group. We examined trivalent influenza vaccine (TIV) efficacy and safety in young children attending childcare. A double-blind, randomised controlled trial in children aged 6 to <48 months was conducted with recruitment from Sydney childcare centres in 2011. Children were randomised to receive two doses of TIV or control hepatitis A vaccine. Efficacy was evaluated against polymerase chain reaction-confirmed influenza using parent-collected nose/throat swabs during influenza-like-illness. Safety outcomes were assessed during 6 months of follow-up. Fifty-seven children were allocated to influenza vaccine and 67 to control; all completed the study. The influenza attack rate was 1.8 vs 13.4% in the TIV and control groups, respectively; VE 87% (95%CI: 0-98%). For children aged 24 to <48 months, 0 vs 8 (18.6%) influenza infections occurred in the TIV and control groups respectively, giving a VE of 100% (16-100%). Efficacy was not shown in children 6 to <24 months, probably due to insufficient power. Injection site and systemic adverse events were mostly mild to moderate with no significant differences, apart from more mild diarrhoea following dose 2 in TIV recipients (11.8 vs 0%). Influenza vaccine appeared efficacious in the subgroup of children aged 24 to <48 months, although caution is required due to the small number of participants. There were no serious adverse events and most parents would vaccinate again. Influenza vaccination in a childcare setting could be valuable and a larger confirmatory study would be helpful.

Immunogenicity, safety and tolerability of inactivated trivalent influenza vaccine in overweight and obese children

Obesity may be a risk factor for increased hospitalization and deaths from infections due to respiratory pathogens. Additionally, obese patients appear to have impaired immunity after some vaccinations. To evaluate the immunogenicity, safety and tolerability of an inactivated trivalent influenza vaccine (TIV) in overweight and obese children, 28 overweight/obese pediatric patients and 23 healthy normal weight controls aged 3–14 years received a dose of TIV. Four weeks after vaccine administration, significantly higher seroprotection rates against the A/H1N1 strain were observed among overweight/obese children compared with normal weight controls (p<0.05). Four months after vaccination, similar or slightly higher seroconversion and seroprotection rates against the A/H1N1 and A/H3N2 strains were detected in overweight/obese than in normal weight children, whereas significantly higher rates of seroconversion and seroprotection against the B strain were found in overweight/obese patients than in normal weight controls (p<0.05 for seroconversion and seroprotection). Geometric mean titers (GMTs) and fold increase against B strains were significantly higher in overweight/obese patients than in normal weight controls 4 months after vaccine administration (p<0.01 for GMT values and p<0.05 for fold increase). The frequency of local and systemic reactions was similar between the groups, and there were no serious adverse events. The results of this study indicate that in overweight and obese children, antibody response to TIV administration is similar or slightly higher than that evidenced in normal weight subjects of similar age and this situation persists for at least 4 months after vaccine administration in the presence of a favorable safety profile.

Effectiveness of Trivalent Influenza Vaccine among Children in Two Consecutive Seasons in a Community in Japan

Influenza vaccination is considered the single most important medical intervention for the prevention of influenza. The dose of trivalent influenza vaccine in children was increased almost double since 2011/12 season in Japan. We estimated the influenza vaccine effectiveness for children 1-11 years of age using rapid test kits in Isahaya City, involving 28,884 children-years, over two consecutive influenza seasons (2011/12 and 2012/13). Children were divided into two groups, vaccinated and unvaccinated, according to their vaccination record, which was obtained from an influenza registration program organized by the Isahaya Medical Association for all pediatric facilities in the city. There were 14,562 and 14,282 children aged from 1-11 years in the city in 2011 and 2012 respectively. In the 2011/12 season, the overall vaccine effectiveness in children from 1-11 years of age, against influenza A and B were 23% [95% confidence interval (CI): 14%-31%] and 20% [95% CI: 8%-31%], respectively. In the 2012/13 season, vaccine effectiveness against influenza A and B was 13% (95% CI: 4%-20%) and 9% (95% CI: -4%-21%), respectively. The vaccine effectiveness was estimated using the rapid diagnosis test kits. Age-stratified estimation showed that vaccine effectiveness was superior in younger children over both seasons and for both virus types. In conclusion, the trivalent influenza vaccine has a significant protective effect for children 1-11 years of age against influenza A and B infection in the 2011/12 season and against influenza A infection in the 2012/13 season in a community in Japan.

Establishing the Safety of Influenza Vaccine in Egg-Allergic Individuals

CME EDUCATIONAL OBJECTIVES 1. Understand that trivalent influenza vaccine is safe for patients with egg allergy, including patients with severe egg allergy. 2. Understand that egg-allergic patients no longer require any special precautions to safely receive trivalent influenza vaccine. 3. Recognize that the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices advises that most egg-allergic patients can now receive trivalent influenza vaccine from their primary care physician. Trivalent influenza vaccine is grown in chick embryos and contains residual egg protein (ovalbumin). Historically, trivalent influenza vaccine (TIV) has been contraindicated in egg-allergic individuals (EAI) and the vaccine was withheld in many of these individuals due to the ovalbumin. However, protocols were developed that allowed EAIs to safely receive TIV, including stepwise desensitization, vaccine skin testing, and use of low ovalbumin containing vaccine. In the past 3 years, several groups have systematically disproven that EAI are at any increased risk for an allergic reaction than the general population and withholding TIV is not necessary. To date, approximately 4,315 patients have safely received 4,872 total doses of TIV, including 656 EAI with severe egg allergy (including anaphylaxis to egg) who safely received 740 doses of TIV. Thus, it is as safe to provide TIV to EAI as providing it to a non-EAI. This article will trace the evolution of this practice.

H1N1 Antibody Persistence 1 Year After Immunization With an Adjuvanted or Whole-Virion Pandemic Vaccine and Immunogenicity and Reactogenicity of Subsequent Seasonal Influenza Vaccine: A Multicenter Follow-on Study

We investigated antibody persistence in children 1 year after 2 doses of either an AS03(B)-adjuvanted split-virion or nonadjuvanted whole-virion monovalent pandemic influenza vaccine and assessed the immunogenicity and reactogenicity of a subsequent dose of trivalent influenza vaccine (TIV). Children previously immunized at age 6 months to 12 years in the original study were invited to participate. After a blood sample was obtained to assess persistence of antibody against swine influenza A/H1N1(2009) pandemic influenza, children received 1 dose of 2010/2011 TIV, reactogenicity data were collected for 7 days, and another blood sample was obtained 21 days after vaccination. Of 323 children recruited, 302 received TIV. Antibody persistence (defined as microneutralization [MN] titer ≥1:40) 1 year after initial vaccination was significantly higher in the AS03(B)-adjuvanted compared with the whole-virion vaccine group, 100% (95% confidence interval [CI], 94.1%-100%) vs 32.4% (95% CI, 21.5%-44.8%) in children immunized <3 years old and 96.9% (95% CI, 91.3%-99.4%) vs 65.9% (95% CI, 55.3%-75.5%) in those 3-12 years old at immunization, respectively (P < .001 for both groups). All children receiving TIV had post-vaccination MN titers ≥1:40. Although TIV was well tolerated in all groups, reactogenicity in children <5 years old was slightly greater in those who originally received AS03(B)-adjuvanted vaccine. This study provides serological evidence that 2 doses of AS03(B)-adjuvanted pandemic influenza vaccine may be sufficient to maintain protection across 2 influenza seasons. Administration of TIV to children who previously received 2 doses of either pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain.

Risk of convulsions in children after monovalent H1N1 (2009) and trivalent influenza vaccines: A database study

The monovalent H1N1 (2009) pandemic influenza vaccine used predominantly in the UK in 2009/10 was a split virion vaccine with a novel oil-in-water adjuvant (ASO3). While this was highly immunogenic it was also reactogenic especially for fever in children. There is a paucity of comparative data on reactogenicity of trivalent influenza vaccine (TIV). Using the General Practice Research Database (GPRD) we investigated whether there was an increased risk of convulsions in children vaccinated with monovalent H1N1 influenza vaccine in the 2009/10 season and also the risk after vaccination with the seasonal TIVs using the self-controlled case-series method. A total of 2366 children aged under 10 years with at least one convulsion recorded in the GPRD and who had received at least one influenza vaccine at anytime (2858 doses of TIV and 1895 doses of the monovalent H1N1 influenza vaccine) were identified between May 2000 and April 2010. Over this period these 2366 children had a total of 3846 convulsion episodes. There was no increase in the incidence rate ratio (IRR) in the week after vaccination for either the monovalent H1N1 influenza vaccine (IRR 0.99, 95% CI 0.61-1.60) or the first dose of TIV (IRR 0.89, 95% CI 0.53-1.52). A signal of an elevated risk in the first few days after the second dose of monovalent H1N1 influenza vaccine was seen with an IRR for days 1-3 post vaccination of 3.48 (95% CI 0.86-14.07). This is consistent with findings of increased fever in a clinical trial. These results neither provide evidence of an increased risk of convulsions following TIV over a 10-year surveillance period nor following a single dose of the ASO3 adjuvanted monovalent H1N1 vaccine in 2009/10.

Immunogenicity and safety of intradermal influenza vaccine in children

In order to compare the immunogenicity and safety of different doses of trivalent influenza vaccine (TIV) administered intradermallly (ID) with those evoked by a full dose of intramuscular (IM) virosomal-adjuvanted influenza vaccine (VA-TIV), 112 previously primed healthy children aged ≥ 3 years were randomised to receive 9 μg or 15 μg of each strain of ID-TIV, or a full IM dose (15 μg of each strain) of VA-TIV. The A/H1N1 and A/H3N2 seroconversion and seroprotection rates were ≥ 90% and geometric mean titres (GMTs) increased 3.2-14.9 times without any statistically significant between-group differences; however, the seroconversion and seroprotection rates against the B strain were significantly higher in the children receiving either ID-TIV dose (p<0.05) without any differences between them. GMT against B virus was significantly higher in the children receiving the highest dose (p<0.05). Local reactions were significantly more common among the children receiving either ID-TIV dose (p<0.05), but systemic reactions were relatively uncommon in all three groups. Our findings suggest that ID-TIV with 15 μg of each viral antigen can confer a significant better protection against influenza than that obtained with the same dose of IM TIV in already primed children aged ≥ 3 years with an acceptable safety profile. The lower dose of ID-TIV needs further evaluation to analyze persistence of protection.

Absence of cross-reactive antibodies to influenza A (H1N1) 2009 before and after vaccination with 2009 Southern Hemisphere seasonal trivalent influenza vaccine in children aged 6 months-9 years: a prospective study

Please cite this paper as: McVernon et al. (2010) Absence of cross‐reactive antibodies to influenza A (H1N1) 2009 before and after vaccination with 2009 Southern Hemisphere seasonal trivalent influenza vaccine in children aged 6 months–9 years: a prospective study. Influenza and Other Respiratory Viruses 5(1), 7–11. Background Early outbreaks of the pandemic influenza A (H1N1) 2009 virus predominantly involved young children, who fuelled transmission through spread in homes and schools. Seroprevalence studies conducted on stored serum collections indicated low levels of antibody to the novel strain in this age group, leading many to recommend priority immunisation of paediatric populations. Objectives In a prospective study, we sought evidence of cross‐reactive antibodies to the pandemic virus in children who were naïve to seasonal influenza vaccines, at baseline and following two doses of the 2009 Southern Hemisphere trivalent influenza vaccine (TIV). Patients/Methods Twenty children were recruited, with a median age of 4 years (interquartile range 3–5 years); all received two age appropriate doses of TIV. Paired sera were collected pre‐ and post‐vaccination for the assessment of vaccine immunogenicity, using haemagglutination inhibition and microneutralisation assays against vaccine‐related viruses and influenza A (H1N1) 2009. Results Robust responses to H3N2 were observed regardless of age or pre‐vaccination titre, with 100% seroconversion. Fewer seroconverted to the seasonal H1N1 component. Only two children were weakly seropositive (HI titre 40) to the pandemic H1N1 strain at study entry, and none showed evidence of seroconversion by HI assay following TIV administration. Conclusions Administration of 2009 Southern Hemisphere TIV did little to elicit cross‐reactive antibodies to the pandemic H1N1 virus in children, in keeping with assay results on stored sera from studies of previous seasonal vaccines. Our findings support the recommendations for influenza A (H1N1) 2009 vaccination of children in preparation for the 2010 winter season.

Immunogenicity and Safety of H5N1 A/Vietnam/1194/2004 (Clade 1) AS03-Adjuvanted Prepandemic Candidate Influenza Vaccines in Children Aged 3 to 9 Years

The development of vaccines against pandemic influenza viruses for use in children is a public health priority. In this phase II, randomized, open study, the immunogenicity and reactogenicity of H5N1 A/Vietnam/1194/2004 (NIBRG-14) (clade 1) prepandemic influenza vaccine were assessed in children aged 3 to 5 and 6 to 9 years. Children were randomized to receive 2 doses, given 21 days apart, of A/Vietnam/1194/2004 vaccine containing 1.9 microg or 3.75 microg hemagglutinin antigen (HA), adjuvanted with a tocopherol-based oil-in-water emulsion (AS03) containing 11.86 mg (AS03(A)) or 5.93 mg (AS03(B)) tocopherol. Control groups received 2 doses of trivalent influenza vaccine (TIV). Humoral immune responses, reactogenicity, and safety were the primary outcome measures; cross-reactivity and cell-mediated responses were also assessed (NCT00502593). Between 49 and 51 children in each age stratum (aged 3-5 and 6-9 years) received H5N1 vaccine, and between 17 and 18 children in each age stratum received TIV. After the second dose, recipients of H5N1 vaccine (1.9 microg HA/AS03(B), 3.75 microg HA/AS03(B), and 3.75 microg HA/AS03(A)) achieved humoral antibody titers against the vaccine-homologous strain, which fulfilled the United States influenza vaccines licensure criteria for immunogenicity. With the exception of 1 child, there were no H5N1 immune responses in children who received TIV. The most frequent injection-site event was pain in all groups, and the H5N1 vaccine had a clinically acceptable reactogenicity and safety profile. Exploratory analyses in children aged 3 to 5 years indicated that the induction of CD4 T-cell responses polarized in favor of a T-helper 1 profile. The results showed that 2 doses of AS03-adjuvanted H5N1 influenza vaccine at antigen-sparing doses of 1.9 microg or 3.75 microg HA elicited broad and persistent immune responses with acceptable reactogenicity, and without safety concerns, in children aged 3 to 9 years.

Immune Response to Influenza Vaccine in Pediatric Patients With Inflammatory Bowel Disease

The aim of this study was to compare response to inactivated influenza vaccine in healthy children and pediatric patients with inflammatory bowel disease (IBD). A prospective, open-label, controlled clinical trial during influenza seasons of 2002-2004 was performed. Single-dose inactive trivalent influenza vaccine was administered. Immune response to vaccination was measured by pre-immunization and postimmunization hemagglutinin inhibition titers. A postimmunization hemagglutinin inhibition titer of 40 or higher was considered protective against influenza. IBD activity and adverse events were recorded. Eighty subjects were enrolled (29 healthy controls, 51 IBD patients). One patient did not complete the study. Patients were divided into 3 subgroups: infliximab and immunomodulatory (16), immunomodulatory (20), and anti-inflammatory therapy (14). Immunomodulatory therapy included corticosteroids, 6-mercaptopurine, or methotrexate. Overall, there was a statistically significant decrease in immune response in patients compared with healthy controls who received 1 influenza vaccine antigen (B/Hong Kong, P = .0125). Patients receiving infliximab and immunomodulatory therapy were less likely to respond to 2 influenza vaccine antigens (A/New Caledonia/20/99 and B/Hong Kong/330/2001, P = .018 and .0002, respectively). Fifteen subjects (19%) reported 19 mild adverse events: 11 (14%) reported soreness at the site, 4 (5%) reported having a cold, 3 (4%) reported flu-like symptoms, and 1 (1%) reported a headache. The clinical activity of IBD was not affected by vaccination. The serologic conversion rate to influenza vaccine in patients with IBD ranged from 33% to 85%. Patients on concomitant infliximab and immunomodulatory therapy are at risk of inadequate response to vaccination. The vaccine was safe and did not affect IBD activity.

The Safety of Trivalent Influenza Vaccine Among Healthy Children 6 to 24 Months of Age

The objective of this study was to assess the safety of routine trivalent influenza vaccine (TIV) administration among healthy children 6 through 23 months of age, after the Advisory Committee on Immunization Practices recommendation. The study was a retrospective case-control study of children receiving TIV in the first 2 seasons after the Advisory Committee on Immunization Practices recommendation. We assessed outcomes in the 42 days after vaccination in a population of 13,383 children. Each case subject was matched, according to age and gender, with 3 control subjects. Hazard ratios were calculated with conditional logistic regression analysis. We found no statistically significantly elevated hazard ratios for the first TIV dose. An elevated risk of pharyngitis was found for children receiving a second TIV dose. No elevated risk of seizure was found. These results, for a population of healthy children, showed no medically significant adverse events related to TIV among children 6 to 23 months of age.

A virosome vaccine antigen delivery system does not stimulate an antiphospholipid antibody response in humans

A virosome vaccine delivery system comprised of the hemagglutinin of influenza A virus incorporated into unilamellar liposomes consisting of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) or only PC was developed. The anti-PE and anti-PC antibody response was determined for human volunteers immunized with a virosome-formulated vaccine against hepatitis A, or a standard or virosome-formulated influenza vaccine. None of the 100 young adults who received two doses of the hepatitis A vaccine 1 year apart mounted a significant (greater than fourfold) antiphospholipid antibody response. Immunization with a single dose of trivalent influenza vaccine engendered a significant anti-PC and anti-PE antibody response in 1 of 32 elderly nursing home residents who received the virosome-formulated influenza vaccine and in 1 of the 31 residents who received a commercial subunit vaccine. These findings indicate that the virosome system can potentiate the human immune response to vaccine antigens without a concomitant rise in antiphospholipid antibodies.

Immunogenicity of a single dose of trivalent influenza vaccine including A/Philippines (H3N2): results of a field trial.

During 1982, a new A(H3N2) influenza virus subtype, A/Philippines/2/82, was identified, and this strain was combined with previous A(H1N1) and B influenza virus strains in the trivalent inactivated vaccine recommended for the 1983-1984 influenza season. Prior to the widescale use of this vaccine in Israel, a group of 106 young male soldiers was vaccinated under controlled conditions. Before vaccination, antibody titers greater than or equal to 1:40 were found in 14.1% against A/Philippines (H3N2), 18.1% against A/England/333/80 (H1N1), and 13.3% against B/Singapore/222/79. Two weeks following vaccination, 78.9% of the vaccinees for whom repeated blood samples were available, had antibody titers in this range for A/Philippines (H3N2), 92.9% for A/England (H1N1), and 80.0% for B/Singapore. The vaccine was only mildly reactogenic, and there were no cases of absence from work following vaccination. Thus the antibody response of young subjects to a single dose of a vaccine containing a new A(H3N2) subtype was found to be satisfactory, and the side effects experienced were minimal.

Immune response of adults to sequential influenza vaccination.

Annual immunization against influenza is recommended for numerous individuals, but the antibody response to sequential vaccination has not been well characterized. Levels of hemagglutination-inhibition antibody were measured in adults given either two or three doses of trivalent influenza vaccine at six-month intervals. A significant rise in the number of individuals with antibody titers of greater than or equal to 40 was seen for all three antigens only after initial vaccination. Repeated vaccination was necessary to maintain adequate antibody levels only to the A/Brazil (H1N1) antigen; it did not significantly affect the proportions of individuals with protective levels of antibody to either the A/Bangkok (H3N2) or the B/Singapore 222/79 antigens. These findings do not support the current recommendation for annual immunization when the vaccine formulation has not changed.