The results of the haemagglutination-inhibiting (HI) antibody test for influenza virus antibody in human sera closely match those produced by virus neutralization assays and are predictive of ...protection. On the basis of the data derived from 12 publications concerning healthy adults, we estimated the median HI titre protecting 50% of the vaccinees against the virus concerned at 28. This finding supports the current policy requiring vaccines to induce serum HI titres of > or = 40 to the vaccine viruses in the majority of the vaccinees. Unfortunately similar studies are scanty for the elderly, the group most at risk of influenza. There still remain many unsolved technical problems with the HI assay and we recommend that these problems be studied and the virus neutralization test as a predictor of resistance to influenza be assessed. Although the studies on this issue often give conflicting results, they generally show that HI antibody responses to influenza vaccination tend to diminish with increasing age, when health is often compromized. Advanced age in itself seems not to be an independent factor in this process. However, even in completely healthy elderly individuals the response to vaccination with an antigenically new virus may be strongly reduced compared with younger vaccinees.
Current available influenza vaccines are safe and effective in preventing influenza. Nevertheless, there is a need for influenza vaccines with improved efficacy in the elderly. This need is ...underscored by both the observation that influenza has a major clinical and economic impact in the elderly and the fact that currently available vaccines are generally less effective in elderly than in younger subjects. Several approaches are currently being pursued in order to improve the efficacy of influenza vaccines in elderly individuals and others who have impaired immune responses to conventional influenza vaccines. A novel antigen-presenting strategy to overcome impaired immune responses is the use of virosomes. Previously, data on safety and reactogenicity have been published regarding the use of virosomal influenza vaccines. Data from three recent clinical trials are presented here. The first of these was a comparative study of a virosomal vaccine and a conventional subunit vaccine in “at-risk” adults with underlying chronic illness. The virosomal vaccine demonstrated comparable tolerability to the subunit vaccine, with about 98% of patients reporting tolerability to be good or very good. The vast majority of adverse events reported were mild to moderate in severity. With both vaccine types, mean HI titres decreased with age for both the A-H
1N
1 and B influenza virus strains, but for the A-H
3N
2 strain (the most virulent of the three strains), mean HI titres did not decrease with age, suggesting a better response with the virosomal vaccine when compared to the subunit vaccine. All three studies explored the long-term persistence of antibodies after vaccination with virosomal influenza vaccines. Immunogenicity declined over time but remained high at 4, 6 and 12 months post-vaccination compared to baseline, indicating that adequate seroprotection is achievable for the duration of the influenza season. Virosomal vaccines may induce better immunity in elderly subjects and may be more effective in reducing morbidity and mortality in this age group.
The medical and economic burden associated with annual influenza activity is well known and well documented. Yearly updated influenza vaccines are available to combat the disease and its ...consequences. In many countries, less than half of the high risk patients are being vaccinated, despite recommendations to do so by national health authorities. Scientific evidence on the safety, tolerance, efficacy and effectiveness of currently existing inactivated influenza vaccines unambiguously demonstrates the favourable benefit/risk ratio of influenza immunisations for high risk patients and strongly suggests an economic benefit of influenza immunisation programmes. Because of both the successful world-wide efforts of the WHO to optimise the chance of an adequate antigenic match between vaccine and epidemic strains each year and the available scientific data about the inactivated influenza vaccines, influenza immunisations should be offered annually to high risk patients. On the basis of the available evidence, offering a vaccination to such patients should be considered an ethical obligation.
Sir, Drs. Couch et al. have recently published a randomized vaccination trial in ambulatory elderly assessing reactogenicity and antibody response to inactivated trivalent influenza vaccine with ...dosages of either 15μg (standard) or 60μg hemagglutinin (HA) per strain 1.
A tissue culture method using MDCK cells grown under serum-free conditions was developed to produce an inactivated influenza subunit vaccine. The first clinical data suggest it to be equal to the ...conventional egg-derived influenza subunit vaccine. In a double-blind controlled trial, 2 groups (n = 57 each) of adult volunteers were immunized with experimental bivalent influenza subunit vaccine derived from either MDCK cells or hens' eggs. Each vaccine contained 15 μg of hemagglutinin of influenza A/Taiwan/1/86 (H1N1) and 15 μg of hemagglutinin of B/Panama/ 45/90. No clinically relevant adverse reactions were observed in either vaccine group, and the incidence of systemic and local vaccine reactions was comparable in both groups. Standard hemagglutination inhibition antibody titers were determined using both MDCK- and egg-derived test antigens. The data reveal that both vaccines are safe and well-tolerated and meet the criteria for immunogenicity as stated in the European Community's “Harmonisation of Requirements for Influenza Vaccines.”
In 14 clinical studies, various efficacy and safety aspects of a new virosomal influenza vaccine (Invivac
®) were assessed in 2865 subjects. The virosomal influenza vaccine fully complies with the ...Committee for Proprietary Medicinal Products (CPMP) requirement for immunogenicity of influenza vaccines. In particular, in a subset of subjects with low pre-vaccination titers (thus those persons who actually need protection by a vaccine), between 76 and 99% of subjects (dependent on age, health status and vaccine components) achieved protective hemagglutination inhibiting (HI) antibody titers after vaccination with the virosomal influenza vaccine. Acceptable frequencies of well-known local and systemic reactions were observed in healthy adults and risk subjects in clinical studies and in a post-marketing study population. These reactions were transient and generally not severe, and did not cause major inconvenience. In conclusion, Invivac
® is an efficacious and safe vaccine for the protection against influenza in healthy and chronically ill adult subjects. The vaccine is especially efficacious in subjects with low pre-vaccination immunity.
Three cohort studies in adults were performed during the periode from 1986 to 1989. Eight hundred and eighty-four subjects were, one or more times, immunized with influenza vaccines, and pre- and ...post-vaccination antibody titres were determined by hemagglutination inhibition tests. One thousand and one hundred and nineteen vaccination events in 681 subjects could be analysed by a comparison, per trial and per influenza (sub) type, between groups with and without influenza vaccination in previous years. Effect size, odds ratio and protection rate difference, were used as effect measures. Subjects with previous vaccination showed higher pre-vaccination antibody than those without. The average change of the post-vaccination proportion of subjects with high antibody titre value to previous vaccination, was +9.4% (95% CI: +5.3 to 13.6%) for A-H3N2 vaccine components, −2.1% (−8.1 to 3.9%, not significant) for A-H1N1 and −10.6% (−16.5% to −4.8%) for B. In a linear regression model, pre-vaccination titres and the status of previous vaccination were identified as factors significantly influencing post-vaccination titres. These findings are discussed in the context of a short review of the literature. It is concluded that the status of previous vaccination should always be addressed as an independent factor in serological vaccination studies.
Local mucosal IgA antibodies play a central role in protection of the respiratory tract against influenza virus infection. Therefore, new-generation influenza vaccines should aim at stimulating not ...only systemic, but also local antibody responses. Previously, we demonstrated that the recombinant B subunit of the
Escherichia coli heat-labile toxin (LTB) is a potent adjuvant towards nasally administered influenza subunit antigen. Here, we investigated the protection conferred by LTB-supplemented influenza subunit antigen given intranasally (i.n.) or intramuscularly (i.m.) to mice. Both i.n. and i.m. immunization with subunit antigen and LTB completely protected the animals against viral infection. Protection upon i.n. immunization was associated with the induction of antigen-specific serum IgG and mucosal IgA, whereas protection upon i.m. immunization correlated with strong serum
and mucosal IgG, but not IgA responses. We conclude that LTB-supplemented influenza subunit antigen, given either i.n. or i.m, induces protective antibody-mediated mucosal immunity and thus represents a promising novel flu vaccine candidate.
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