Duration of protection provided by live attenuated influenza vaccine in children

BACKGROUND: Reliable availability of influenza vaccine before October could enable the vaccination of many children who might not otherwise be vaccinated. METHODS: Available data for children were analyzed to describe protection provided by live attenuated influenza vaccine (LAIV) for greater than 5 months postvaccination. RESULTS: Four studies conducted in children aged 6 months to 18 years were identified. Culture-confirmed efficacy against A/H1N1 and A/H3N2 strains at 9-12 months postvaccination was 77% [95% confidence interval (CI): 53-89%] to 100% (95% CI: 68-100%) and through a second influenza season without revaccination was 56% (95% CI: 31-73%) and 57% (95% CI: 6-82%), respectively. Against B strains, 1 study demonstrated 86% (95% CI: 59-95%) efficacy at 5-7 months. Another study demonstrated 27% (95% CI: -62% to 67%) efficacy at 9-12 months compared with 74% (95% CI: 39-89%) at 1 to <5 months during a period of antigenic drift for circulating B strains. A third study estimated 50% (95% CI: -49% to 83%) efficacy against influenza B strains through a second season without revaccination. CONCLUSIONS: In children, live attenuated influenza vaccine provided sustained protection against influenza illness caused by antigenically similar strains. Efficacy at 1 to <5 months postvaccination was comparable to that at 9-12 months for A/H1N1 and A/H3N2 strains and at 5-7 months for B strains. Meaningful efficacy was seen through a second season without revaccination, although at a lower level than during the first 12 months postvaccination.     

Augmented antibody response to live attenuated measles vaccine in children with Plasmodium falciparum parasitaemia

The impact of malarial infection on the humoral immunological response to measles virus antigen was studied in 184 children aged 8-19 months in Guinea-Bissau. Pre- and post-immunization measles serology was performed using dried blood on absorbent paper and the ELISA technique. Blood smears obtained at the time of vaccination and 2 and 4 weeks afterwards were examined for malaria parasites. Pre-vaccination antibodies to measles were found in 44 out of 184 children (24%). Plasmodium falciparum was identified in 62 of the 132 initially non-immune children who completed the study. The rate of seroconversion was 127 out of 132 (96%). Post-immunization measles antibody titres were significantly higher in the vaccinees with P. falciparum than in those without malaria parasites in the blood.     

Live attenuated influenza vaccine in children

Live attenuated influenza vaccine (LAIV) offers a novel approach to influenza vaccination and is approved for healthy individuals 5 to 49 years of age. In placebo-controlled studies in children, LAIV was 73 to 93 percent efficacious, and protection lasted more than 12 months. In head-to-head studies in children, LAIV demonstrated a 35 to 53 percent reduction in influenza attack rates compared with injectable influenza vaccine (TIV) for matched strains. Compared with TIV, LAIV has demonstrated broader serum antibody responses, particularly against mismatched influenza A. The most common adverse events are runny nose and nasal congestion. Increased rates of asthma events were observed in young children. Additional large-scale safety and efficacy studies in young children, including a formal risk-benefit assessment, are ongoing. The results of these analyses will guide potential future use in young children.     

Safety of cold-adapted live attenuated influenza vaccine in a large cohort of children and adolescents

OBJECTIVE: To determine the safety of cold-adapted trivalent intranasal influenza virus vaccine (CAIV) in children and adolescents. STUDY DESIGN: A randomized, double blind, placebo-controlled safety trial in healthy children age 12 months to 17 years given CAIV (FluMist; MedImmune Vaccines, Inc.) or placebo (randomization, 2:1). Children <9 years of age received a second dose of CAIV or placebo 28 to 42 days after the first dose. Enrolled children were then followed for 42 days after each vaccination for all medically attended events. Prespecified outcomes included 4 prespecified diagnostic groups and 170 observed individual diagnostic categories. The relative risk and the 2-sided 90% confidence interval were calculated for each diagnostic group and individual category by clinical setting, dose and age. More than 1500 relative risk analyses were performed. RESULTS: A total of 9689 evaluable children were enrolled in the study. Of the 4 prespecified diagnostic categories (acute respiratory tract events, systemic bacterial infection, acute gastrointestinal tract events and rare events potentially associated with wild-type influenza), none was associated with vaccine. Of the biologically plausible individual diagnostic categories, 3, acute gastrointestinal events, acute respiratory events and abdominal pain, had different analyses that demonstrated increased and decreased relative risks, making their association with the vaccine unlikely. For reactive airway disease a significant increased relative risk was observed in children 18 to 35 months of age with a relative risk of 4.06 (90% confidence interval, 1.29 to 17.86) in this age group. The individual diagnostic categories of upper respiratory infection, musculoskeletal pain, otitis media with effusion and adenitis/adenopathy had at least one analysis that achieved a significant increased risk ratio. All of these events were infrequent. CONCLUSION: CAIV was generally safe in children and adolescents. The observation of an increased risk of asthma/reactive airway disease in children <36 months of age is of potential concern. Further studies are planned to evaluate the risk of asthma/reactive airway disease after vaccine.     

减毒流感活疫苗在2～17岁儿童中的有效性和安全性

与接种三价灭活流感疫苗(trivalent inactivated influenza vaccine,TIV)相比较,接种减毒流感活疫苗(live attenuated influenza vaccine,LAIV)能明显提高2～17岁健康儿童及患呼吸道疾病、免疫缺陷病儿童的抗流感能力,能更有效预防儿童流感的发生,且不会提高儿童的急诊率和住院率,不会提高除鼻塞、流涕外,任何其他不良反应的发生率.LAIV能使儿童机体产生更强的抗流感免疫反应.接种LAIV1年后,其仍有较高的保护效力.经鼻腔接种LAIV方便且无痛苦,更容易被儿童和家长所接受.LAIV为预防儿童流感的发生提供了一条有效的途径.     

Response to live attenuated measles vaccine in children with severe kwashiorkor

An impaired response to vaccination with live attenuated measles vaccine was found in severely malnourished children, when compared with well nourished controls. It is suggested that humoral immune response may fail in children with severe protein energy malnutrition due to diversion of available amino acids to other uses. The possibility of a delayed antibody response to measles vaccine in malnourished children was not excluded.     

Superior relative efficacy of live attenuated influenza vaccine compared with inactivated influenza vaccine in young children with recurrent respiratory tract infections

BACKGROUND: Young children have a high incidence of influenza and influenza-related complications. This study compared the efficacy and safety of cold-adapted influenza vaccine, trivalent (CAIV-T) with trivalent inactivated influenza vaccine (TIV) in young children with a history of recurrent respiratory tract infections (RTIs). METHODS: Children 6 to 71 months of age were randomized to receive 2 doses of CAIV-T (n = 1101) or TIV (n = 1086), 35 +/- 7 days apart before the start of the 2002-2003 influenza season and were followed up for culture-confirmed influenza, effectiveness outcomes, reactogenicity, and adverse events. RESULTS: Overall, 52.7% (95% confidence interval [CI] = 21.6%-72.2%) fewer cases of influenza caused by virus strains antigenically similar to vaccine were observed in CAIV-T than in TIV recipients. Greater relative efficacy for CAIV-T was observed for the antigenically similar A/H1N1 (100.0%; 95% CI = 42.3%-100.0%) and B (68.0%; 95% CI = 37.3%-84.8%) strains but not for the antigenically similar A/H3N2 strains (-97.1%; 95% CI = -540.2% to 31.5%). Relative to TIV, CAIV-T reduced the number of RTI-related healthcare provider visits by 8.9% (90% CI = 1.5%-15.8%) and missed days of school, kindergarten, or day care by 16.2% (90% CI = 10.4%-21.6%). Rhinitis and rhinorrhea, otitis media, and decreased appetite were the only events that were reported more frequently in CAIV-T subjects. There was no difference between groups in the incidence of wheezing after vaccination. CONCLUSIONS: CAIV-T was well tolerated in these children with RTIs and demonstrated superior relative efficacy compared with TIV in preventing influenza illness.     

Efficacy and safety of a live attenuated, cold-adapted influenza vaccine, trivalent against culture-confirmed influenza in young children in Asia

BACKGROUND: This study was designed to evaluate the efficacy and safety of cold-adapted influenza vaccine, trivalent (CAIV-T) against culture-confirmed influenza in children 12 to <36 months of age during 2 consecutive influenza seasons at multiple sites in Asia. METHODS: In year 1, 3174 children 12 to <36 months of age were randomized to receive 2 doses of CAIV-T (n = 1900) or placebo (n = 1274) intranasally > or =28 days apart. In year 2, 2947 subjects were rerandomized to receive 1 dose of CAIV-T or placebo. RESULTS: Mean age at enrollment was 23.5 +/- 7.4 months. In year 1, efficacy of CAIV-T compared with placebo was 72.9% [95% confidence interval (CI): 62.8-80.5%] against antigenically similar influenza subtypes, and 70.1% (95% CI: 60.9-77.3%) against any strain. In year 2, revaccination with CAIV-T demonstrated significant efficacy against antigenically similar (84.3%; 95% CI: 70.1-92.4%) and any (64.2%; 95% CI: 44.2-77.3%) influenza strains. In year 1, fever, runny nose/nasal congestion, decreased activity and appetite, and use of fever medication were more frequent with CAIV-T after dose 1. Runny nose/nasal congestion after dose 2 (year 1) and dose 3 (year 2) and use of fever medication after dose 3 (year 2) were the only other events reported significantly more frequently in CAIV-T recipients. CONCLUSIONS: CAIV-T was well tolerated and effective in preventing culture-confirmed influenza illness over multiple and complex influenza seasons in young children in Asia.     

Effect of yearly vaccinations with live,attenuated, cold-adapted,trivalent, intranasal influenza vaccines on antibody responses in children

BACKGROUND: The cold-adapted, trivalent influenza vaccine (CAIV-T) may become an option for annual vaccination. However, there is little information regarding the immune response to repeated immunization with CAIV-T. OBJECTIVE: To determine the antibody response to repeated immunization with CAIV-T and to compare this with the response after the first CAIV-T immunization. DESIGN AND METHODS: Healthy children were offered CAIV-T immunization for 4 consecutive years, and blood samples were taken from a subset in Years 1, 2 and 4. In Year 4, 156 similarly aged children who had not received influenza vaccine previously were immunized with the same CAIV-T. RESULTS: The H3N2 and B components of the CAIV-T induced high antibody titers in Year 1 that were maintained during 4 years. The H1N1 titers were lower than the H3N2 or B titers. Comparison of the group immunized for 4 consecutive years with the group immunized for the first time revealed the following: (1) before immunization yearly immunized subjects were more likely to be seropositive to each of the three vaccine strains than those immunized for the first time (P < 0.05 for each); (2) after immunization the percentage of seropositive subjects to each of the strains was similar; (3) after immunization titers were higher in the subjects immunized for the first time than those immunized yearly (P < 0.05 for H3N2 and B). CONCLUSION: Yearly vaccination with CAIV-T induced high antibody titers, especially to the H3N2 and B strains in the vaccines. The titers in those immunized with CAIV-T for the first time were higher than in those immunized for 4 consecutive years.     

Live attenuated influenza virus vaccine trial in children.

Thirty-four children received intranasally a live attenuated influenza A virus vaccine, and were then followed for six months to evaluate the vaccine safety, immunogenicity, and efficacy. All but one of the 31 children with hemagglutination inhibition (HI) titers less than 64 before inoculation responded with at least a four-fold rise in antibody titer to a single dose of vaccine. One child required two doses. Seven (21%) of the vaccinees also responded with production of nasal neutralizing antibody. The vaccine was well tolerated with few clinical reactions. Two vaccinees developed fever possibly attributable to the vaccine. No transmission of the vaccine virus to any of the 25 unvaccinated contact children was demonstrable. Five months after this vaccine trial an influenza epidemic due to a heterologous influenza A strain occurred in the community. During this outbreak acute febrile and/or respiratory illness occurred in 12 or 52% of the contact controls, and in six or 19% of the vaccinees. In two of these six vaccinees, influenza A infection was confirmed by at least a four-fold increase in HI titer. This study suggests this study suggests that this vaccine is safe, easily administered, highly immunogenic in children, and is protective against a heterologous strain epidemic in the community.     

Live attenuated and inactivated influenza vaccine in school-age children

In 1985, we enrolled 189 school-age children by family in a double-blind study to determine protection against influenza by a single dose of cold-recombinant bivalent A vaccine or commercial trivalent inactivated vaccine compared with placebo. All children in school or day care, 3 to 18 years of age, in an enrolled family received the same preparation. Following vaccination, 60% and 21% of cold-recombinant bivalent A vaccine recipients and 73% and 83% of trivalent inactivated vaccine recipients demonstrated fourfold or greater response in hemagglutination-inhibition antibody titer to A/H1N1 and A/H3N2, respectively. Sixty-seven percent of all trivalent inactivated vaccine recipients demonstrated a fourfold or greater serologic response to H1N1, H3N2, and influenza B following a single dose of vaccine. During the 1985-1986 influenza B/Ann Arbor epidemic, heterotypic protection afforded by the influenza B/USSR component of trivalent inactivated vaccine was 62% compared with placebo. A single dose of trivalent inactivated vaccine protected school-age children, 6 to 19 years of age, from influenza B infection; the rate of protection was 64% against infection and 73% against febrile illness.     

Evaluation of immunogenicity and tolerability of a live attenuated hepatitis a vaccine in Indian children

An open non comparative study of a live attenuated H2 strain Hepatitis A vaccine of Chinese origin was carried out in 143 healthy Indian children aged 1 to 12 years (mean age 4.87 2.76 years; 88 boys, 55 girls). At baseline, all were negative for IgG HAV antibodies and had normal hematological and biochemical indices. Two months after a single dose of the vaccine (given subcutaneously), 137 children (i.e. 95.8 %) developed protective antibodies of IgG > 20 mIU / mL. The hematological and biochemical parameters remained within normal limits. There were no adverse events in any except mild fever in one child. In conclusion, live attenuated H2 strain Hepatitis A vaccine in a single dose was found to be immunogenic and safe in Indian children.     

Safety and immunogenicity of live attenuated varicella vaccine in 9-month-old children

BACKGROUND: The present study was conducted to evaluate the safety and immunogenicity of live attenuated varicella vaccine (Oka-strain) in 9-month-old infants. METHODS: One hundred and fourteen infants were vaccinated once with live attenuated varicella vaccine (Valrix; SmithKline Beecham Biologicals, Rixensart, Belgium) containing a mean virus titer of 10(4.0) plaque-forming units (p.f.u.) per dose. Signs and/or symptoms after vaccination were followed for 42 days. Home visits were made to detect solicited local reactions (0-3 days) and solicited general reactions (0-21 days), as well as unsolicited reactions. Specific varicella antibodies were determined by an indirect immunofluorescence method. The geometric mean titer and seroconversion rate were calculated. RESULTS: Signs and/or symptoms were reported in 47.4% (54/114) of cases following vaccination. The only local symptom reported was pain on digital pressure at the injection site and this was reported in 28.1% (32/114) of infants. General symptoms were reported in 38.6% (44/114) of cases. The most frequently reported findings were fever (27.2%), which was mostly mild, restlessness (20.2%) and cough (11.4%). Only four unsolicited symptoms were reported and they were all unrelated to vaccination. No serious adverse event was reported. Of the 109 infants included in the immunogenicity analysis, 105 were seronegative and four were seropositive for antibodies against varicella before vaccination. The vaccine elicited seroconversion in 97.1% of initially seronegative cases. The post-vaccination geometric mean titer for these infants was 30.9 geometric mean titer (GMT). CONCLUSIONS: The vaccine was found to be safe and immunogenic when given to infants as young as 9 months of age. This may be of clinical significance during outbreaks of varicella and especially for developing countries.