Safety and immunogenicity of trivalent inactivated influenza vaccine in infants: a randomized double-blind placebo-controlled study.

BACKGROUND: Infants less than 6 months of age are at high risk for influenza disease and influenza-related complications, but no vaccine is licensed for this population. METHODS: A double-blind, randomized, placebo-controlled trial was conducted in 1375 healthy US infants 6 to 12 weeks of age. Subjects received 2 doses of trivalent inactivated influenza vaccine (TIV, Fluzone, sanofi pasteur; N = 915) or placebo (N = 460) 1 month apart in combination with indicated concomitant vaccines. Solicited adverse events were collected for 7 days following vaccination, and unsolicited adverse events for 28 days. Hemagglutination-inhibition antibodies to all 3 vaccine strains were measured following the second TIV/placebo dose. RESULTS: No significant differences were seen between TIV and placebo groups for any safety outcome. Fever > or =38 degrees C within 3 days of vaccination was seen in 11.2% versus 11.7% of TIV versus placebo recipients. Serious adverse events within 28 days were reported in 1.9% of TIV and 1.5% of placebo recipients. Antibody responses to childhood vaccines were similar in both groups. Increased influenza-specific antibody responses in TIV recipients compared with placebo recipients were seen against all 3 strains in TIV recipients (P < 0.001), with better responses to influenza A strains noted. Reciprocal geometrical mean titer to H1N1, H3N2, and B were 33, 95, and 11 in TIV recipients versus 7, 9, and 5 for placebo recipients. Over 90% of TIV recipients had antibody > or =1:40 for at least 1 vaccine strain and 49.6% for 2 strains, versus 16.4% and 0.9% in placebo-recipients. CONCLUSIONS: TIV administered to young infants beginning at 6 to 12 weeks of age is safe and immunogenic.

Trivalent inactivated influenza virus vaccine given to two-month-old children: an off-season pilot study.

BACKGROUND: Although children less than 6 months of age have the highest risk for hospitalization related to influenza infection, influenza vaccine is not approved for these children. METHODS: In an open-label, off-season study, healthy 6 to 12 week and 6-month-old children received 2 doses of the 2004 to 2005 trivalent inactivated influenza vaccine (TIV) administered 1 month apart along with other routine pediatric vaccines. Safety was assessed by parental diaries (n = 393). Immunogenicity analyses (n = 293) were performed on sera obtained before vaccination and 1 month after the second dose of TIV. Outcomes included the frequencies of subjects with injection site and systemic reactions and seroprotection rates to TIV antigens. RESULTS: Injection site reactions and fevers were generally mild and resolved within 3 days. Postvaccination seroprotection rates (titer > or = 1:40) in the 6- to 12-week-old and 6-month-old groups were 46% and 69% to A/New Caledonia (H1N1), 59% and 79% to A/Wyoming (H3N2), and 5% and 22% to B/Jiangsu (P < 0.001, all comparisons). For seronegative 6- to 12-week-olds whose mothers had not received TIV during pregnancy, postvaccination seroprotective titers to A/New Caledonia (H1N1) were achieved in 70% (38/54) and to A/Wyoming (H3N2) in 68% (23/34) of infants. CONCLUSIONS: TIV was well tolerated and safe when administered to children at both 6 to 12 weeks and 6 months of age. The antibody response was lower in the younger children, probably related to antibody suppression from passively acquired antibodies from mothers. In 6- to 12-week-olds without preexisting antibody, seroresponses to influenza A antigens approached those of 6-month-old children.

Safety and immunogenicity of a high dosage trivalent influenza vaccine among elderly subjects.

To improve immune responses to influenza vaccine, a trivalent inactivated vaccine containing 60 microg of the HA of each component (A/H3N2, A/H1N1, B) was compared to a licensed vaccine containing 15 microg of the HA of each. More local and systemic reactions were reported by subjects given the high dosage but only local pain and myalgias were significantly increased. The high dosage vaccine induced a higher frequency of serum antibody increases (> or =4-fold) in both hemagglutination-inhibiting (HAI) and neutralization tests for all three vaccine viruses in the total group as well as subjects vaccinated and those not vaccinated the previous year. Mean titers of antibody attained, the magnitude of antibody increases and the frequencies of persons with final HAI antibody titers > or =1:32, > or =1:64, and > or =1:128 were all greater for the high dosage group in both serologic tests, for all groups, and for all vaccine viruses. These increased immune responses should provide increased protection against influenza in the elderly.

Immunogenicity and safety of inactivated influenza virus vaccine in young children in 2003-2004.

This study assessed the safety and immunogenicity of a pediatric formulation of the 2003-2004 inactivated, trivalent, split virion influenza vaccine, administered in a 2-dose schedule in healthy children ages 6-36 months, of whom 94% had protective titers (> or =1/40) to at least 1 antigen. The 2003-2004 split virion influenza vaccine was safe and immunogenic in young children.

Inactivated influenza virus vaccines in children.

Healthy children aged < or =2 years have hospitalization rates during influenza periods 12 times those of older children and comparable to rates in the elderly population. In 2003, killed influenza vaccines were "recommended" for children with high-risk conditions and were "encouraged" for children aged 6-23 months. Studies involving several thousand children show that split-virus vaccines are safe and immunogenic in healthy children aged > or =6 months and in high-risk children. In children aged < or =9 years, 2 doses of vaccine are required initially to achieve maximum protection. Studies of children aged 6 months to 15 years show vaccine efficacies of 31%-91% against influenza A and 45% against influenza B. Among children attending day care, a reduction in the rate of acute otitis media of 32%-36% was demonstrated. Studies suggest that use of killed vaccines among children is cost-saving. In conclusion, the data show that killed influenza vaccines in children are safe, immunogenic, effective, and potentially cost-saving.

Maritime health: a case for preventing influenza on the high seas.

For decades cruise ships have been recognized as foci for diarrheal illness. More recently influenza has been added to the list of diseases for which people on cruise ships are at risk. Influenza is a business risk involving cruise ship operating and litigation costs and travelers' loss in value. Immunizing the crews could be one way to prevent introduction and spread of influenza on cruise ships. A cost-effectiveness analysis for vaccination of crews on cruise ships was conducted showing that it is not only cost-effective but it is cost savings.

Immediate hypersensitivity reactions after use of tuberculin skin testing.

This report describes the frequency and characteristics of serious or life-threatening hypersensitivity reactions to the tuberculin skin test over an 11-year period through November 2000. There were 24 reports and no deaths, indicating that such reactions are rare (0.08 reported reactions per million doses of tuberculin).