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BACKGROUND: Influenza A H5N1 viruses pose a significant threat to human health. METHODS: We conducted a multicenter, randomized, double-blind study in 394 healthy adults. Subjects were randomly assigned to receive 2 intramuscular doses of either saline placebo; influenza A/Vietnam/1203/2004(H5N1) vaccine alone at 45, 30, or 15 microg per dose; vaccine at 15 or 7.5 microg per dose with MF59; or vaccine at 30, 15, or 7.5 microg per dose with aluminum hydroxide. Subjects were followed up for safety and blood samples were obtained to determine antibody responses. RESULTS: The vaccine formulations were well tolerated but local adverse effects were common; the incidence of these effects increased in a dose-dependent manner and was increased by the addition of adjuvants. The addition of MF59 increased the antibody response, whereas the addition of aluminum hydroxide did not. The highest antibody responses were seen in the group that received 15 microg of vaccine per dose with MF59, in which 63% of subjects achieved the predetermined endpoint (hemagglutination-inhibition titer > or =40) 28 days after the second dose, compared with 29% in the group that received the highest dose (45 microg per dose) of vaccine alone. CONCLUSIONS: A 2-dose regimen of subvirion influenza A (H5N1) vaccine was well tolerated. The antibody responses to 15 microg of A/H5 vaccine with MF59 were higher than the responses to 45 microg of vaccine alone. TRIAL REGISTRATION: ClincalTrials.gov identifier: http://www.clinicaltrials.gov/ct2/show/NCT00280033?term= NCT00280033&rank=1 NCT00280033 .nCopyright © 2008 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

In most years epidemics of influenza cause a significant increase in morbidity and mortality worldwide. With the availability of a new class of antivirals targeting the viral protein neuraminidase, there are new options for the control of influenza. The use of the older antiviral agents (M2 inhibitors: amantadine and rimantadine) is limited because of lack of activity against influenza B viruses, unfavourable tolerability in the case of amantadine and rapid emergence of resistance in a substantial proportion of treated persons. Neuraminidase inhibitors (NAIs) are potent and selective drugs that inhibit influenza neuraminidase, an enzyme that promotes the release of influenza virus from infected cells and facilitates virus spread within the respiratory tract. In contrast to the M2 inhibitors, NAIs have broader anti-influenza activity, better tolerance than amantadine and the frequency of resistance emergence is expected to be lower based on the lower incidence of resistant isolates emerging during the clinical trials. NAIs provide an important new option for the treatment of influenza and will play an important role in its management. Although the current data on viral resistance are very reassuring, it will be important to continue to monitor the broad use of NAIs in general practice. Therefore, collaborative virological surveillance systems have been set up to monitor the use of NAIs in clinical practice. [ABSTRACT FROM AUTHOR]

Editorial. Comments on advances in fundamental influenza virology research. Availability of tools to prevent and treat influenza in 1999/2000; Genetic segments of influenza viruses; Antigens contained in the 1999/2000 influenza vaccine.

Context: Influenza virus is a major cause of illness, disruption to daily life, and increased use of health care in all age groups.Objective: To assess the safety and effectiveness of intranasally administered trivalent, live, attenuated influenza virus (LAIV) vaccine for reducing illness, absenteeism, and health care use among healthy, working adults.Design: Randomized, double-blind, placebo-controlled trial conducted from September 1997 through March 1998.Setting: Thirteen centers across the United States.Participants: A total of 4561 healthy, working adults aged 18 to 64 years recruited through health insurance plans, at work sites, and from the general population.Intervention: Participants were randomized 2:1 to receive intranasally administered trivalent LAIV vaccine (n = 3041) or placebo (n = 1520) in the fall of 1997.Main Outcome Measures: Episodes of febrile illness, severe febrile illness, febrile upper respiratory tract illness, work loss, and health care use during the peak and total influenza outbreak periods, and adverse events.Results: Recipients of LAIV vaccine were as likely to experience 1 or more febrile illnesses as placebo recipients during peak outbreak periods (13.2% for vaccine vs 14.6% for placebo; P=.19). However, vaccination significantly reduced the numbers of severe febrile illnesses (18.8% reduction; 95% confidence interval [CI], 7.4%-28.8%) and febrile upper respiratory tract illnesses (23.6% reduction; 95% CI, 12.7%-33.2%). Vaccination also led to fewer days of illness across all illness syndromes (22.9% reduction for febrile illnesses; 27.3% reduction for severe febrile illnesses), fewer days of work lost (17.9% reduction for severe febrile illnesses; 28.4% reduction for febrile upper respiratory tract illnesses), and fewer days with health care provider visits (24.8% reduction for severe febrile illnesses; 40.9% reduction for febrile upper respiratory tract illnesses). Use of prescription antibiotics and over-the-counter medications was also reduced across all illness syndromes. Vaccine recipients were more likely to experience runny nose or sore throat during the first 7 days after vaccination, but serious adverse events between the groups were not significantly different. The match between the type A(H3N2) vaccine strain and the predominant circulating virus strain (A/Sydney/05/97[H3N2]) for the 1997-1998 season was poor, suggesting that LAIV provided substantial cross-protection against this variant influenza A virus strain.Conclusion: Intranasal trivalent LAIV vaccine was safe and effective in healthy, working adults in a year in which a drifted influenza A virus predominated. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the influence of a human immunodeficiency virus (HIV) vaccine given to uninfected volunteers on the interpretation of serodiagnostic HIV test results.Design: Retrospective cohort study.Setting: 5 AIDS Vaccine Evaluation Units funded by the National Institute of Allergy and Infectious Diseases.Participants: The first 266 healthy adult volunteers (aged 18 to 60 years) who did not have HIV infection and whose history suggested that they were at low risk for acquiring HIV infection.Measurements: HIV antibody was measured by enzyme-linked immunosorbent assay (ELISA) and Western blot test, the results of which were interpreted on the basis of four different published criteria.Results: At some time during the first 12 months of the vaccine studies, 68% of volunteers were positive for HIV antibodies by ELISA. Depending on criteria used to interpret Western blot test results, 0% to 44% of volunteers had positive results that might have caused them to be incorrectly labeled as HIV infected.Conclusions: Significant social risks to volunteers participating in HIV vaccine studies were identified. Persons interpreting HIV serodiagnostic test results must consider that an HIV vaccine can cause a positive result in persons who are not infected. [ABSTRACT FROM AUTHOR]