Three papers by Hoskins and collaborators published in
The Lancet in the 70s, have been challenging the common policy to annually vaccinate people at risk with inactivated influenza virus vaccine. ...From an analysis of a vaccination campaign in adolescent pupils of a boarding school and four influenza outbreaks in the period 1970–1976, Hoskins
et al. concluded that annually repeated vaccinations would not confer protection against epidemic influenza in the long-term (‘Hoskins' Paradox’). A review of the papers revealed, however, that most of the study subjects were not consequently vaccinated every year and that most of the presented data were, therefore, not relevant for the problem of annually repeated influenza vaccination. When applying strict definitions of single vaccination (immunised immediately prior to the epidemic, but not in the years before) and multiple vaccination (immunised immediately prior to the epidemic, and also in the year(s) before), only two of four epidemics (A/England/42/72 (H3N2) in 1972/73 and A/Port Chalmers/1/73 (H3N2) in 1973/74) could be evaluated: in one case, no negative effect of repeated vaccination could be detected, in the second case, the attack rate difference between groups with single and multiple vaccination was of borderline significance. Data on two other epidemics (B/Hong Kong/8/73 in 1973/74 and A/Victoria/3/75 (H3N2) in 1975/76) could not be interpreted because of incomplete vaccination strategies. In conclusion, Hoskins' Paradox cannot be substantiated by Hoskins' own data. Considering other published data on the subject, it is suggested that no negative effect of annually repeated vaccination on protection against epidemic influenza exists.
According to common recommendations, influenza vaccination should be performed annually. It has been suggested that vaccination in previous years reduces vaccine efficacy in the long term.
To ...determine whether the protection of influenza vaccine decreases when vaccination is repeated annually.
Articles published between 1966 and 1997 were selected from MEDLINE. The end point for field studies was the influenza-related morbidity or mortality during influenza outbreaks (resulting in field protection rates). The end point for serologic studies was exceeding a protective postvaccination hemagglutination-inhibition titer (serologic protection rates). Protection rate differences between groups with single and multiple vaccinations were subjected to meta-analysis.
Seven field studies (including 13 trials) supported the hypothesis that protection in multiple-vaccination groups is at least as good as that in single-vaccination groups. Ten trials with 5117 observations could be subjected to meta-analysis. The pooled protection-rate difference was close to 0 (1.1%; 95% confidence interval, -0.2% to 2.4%), thus detecting no difference between single or multiple vaccination. Twelve serologic studies (including 53 trials) showed heterogeneous results: 9 trials were significantly in favor of single vaccination, and 7 were in favor of multiple vaccination, but in most cases, there was no significant difference between the 2 vaccination groups. The pooled serologic protection-rate difference from 52 trials (12341 observations) was again close to 0 (1.7%; 95% confidence interval, -1.3% to 4.8%).
We did not detect any evidence for a decreasing protection with annually repeated influenza vaccination. Annual vaccination should not be discouraged in populations at risk.
To investigate the effects of age and antigen dose (10, 20, 60 micrograms) on the immunoglobulin (sub) class distribution following influenza vaccination, antibody responses in 79 elderly nursing ...home residents were compared with the responses in 100 young subjects. At a 10 micrograms dose the IgM, IgG3 and IgA1 responses were comparable in both age groups, whereas the IgG, IgG1 and haemagglutination inhibition (HI) responses were twofold lower in the elderly. A 20 micrograms dose increased the IgG, IgG1 and HI levels in the elderly to the levels in the young and the IgA1 to significantly higher levels. A 60 micrograms dose increased antibody levels in the young, but did not further increase the response in the elderly. The 20 micrograms dose might represent a higher level of protection in the elderly.
There is a need for more efficacious inactivated influenza vaccines, since current formulations show suboptimal immunogenicity in at-risk populations, like the elderly. More effective vaccines are ...also urgently needed for an improved influenza pandemic preparedness. In this context, there is considerable interest in virosomes. Virosomes are virus-like particles, consisting of reconstituted influenza virus envelopes, lacking the genetic material of the native virus. Virosomes are produced from influenza virus through a detergent solubilization and removal procedure. Properly reconstituted virosomes retain the cell binding and membrane fusion properties of the native virus, mediated by the viral envelope glycoprotein haemagglutinin. These functional characteristics of virosomes form the basis for their enhanced immunogenicity. First, the repetitive arrangement of haemagglutinin molecules on the virosomal surface mediates a cooperative interaction of the antigen with Ig receptors on B lymphocytes, stimulating strong antibody responses. In addition, virosomes interact efficiently with antigen-presenting cells, such as dendritic cells, resulting in activation of T lymphocytes. In a murine model system, virosomes, as compared to conventional subunit vaccine, which consists of isolated influenza envelope glycoproteins, induce a more balanced T helper 1 versus T helper 2 response, virosomes in particular eliciting stronger T helper 1 responses than subunit vaccine. Also, as a result of fusion of the virosomes with the endosomal membrane, part of the virosomal antigen gains access to the major histocompatibility class I presentation pathway, thus priming cytotoxic T lymphocyte activity. Finally, virosomes represent an excellent platform for inclusion of lipophilic adjuvants for further stimulation of vaccine immunogenicity. By virtue of these characteristics, virosomes represent a promising novel class of inactivated influenza vaccines, which not only induce high virus-neutralizing antibody titres, but also prime the cellular arm of the immune system.
Objective. In SLE, a decreased antibody response on influenza vaccination has been reported. In this study, we assessed whether a booster vaccination could improve antibody responses, as determined ...by seroprotection rates, in SLE patients. Methods. SLE patients (n = 52) with quiescent disease (SLEDAI ⩽4) and healthy controls (HCs) (n = 28) received subunit influenza vaccine in October–December 2007. After 4 weeks, only SLE patients received a second dose of vaccination. Sera were obtained before both vaccinations, and 4 weeks after the second vaccination. At each visit, SLE disease activity was recorded. The haemagglutination inhibition test was used to measure antibody titres. Seroprotection was defined as a titre ⩾40. Results. Following the first vaccination, seroprotection rates and geometric mean titres (GMTs) to each vaccine strain increased in both SLE patients and controls to comparable levels. Seroprotection rates in SLE patients after the first vaccination were 86.5% to A/H1N1, 80.8% to A/H3N2 and 61.5% to the B-strain while GMTs were 92.6, 56.2 and 39.2, respectively. Overall, the booster vaccination did not lead to a further rise of seroprotection rates and GMTs in SLE patients. However, in patients not vaccinated in the previous year, GMT and seroconversion rate to A/H1N1 did rise following the booster vaccination. Both influenza vaccinations did not increase SLEDAI scores. Conclusions. Additional value of a booster influenza vaccination in SLE is limited to patients who were not vaccinated in the previous year.
The dose effect (0, 10, 20 and 60 micrograms) of influenza subunit vaccine on the antibody response was investigated in nursing-home residents and young controls. The vaccine antigens were: ...A/Taiwan/1/86 (H1N1), A/Sichuan/2/87 (H3N2) and B/Beijing/1/87. For the influenza B antigen, the post-GMT and the 'percentage protective titre' increased significantly both in the young controls and nursing-home residents. No dose effect was observed for the A/Taiwan, and a minor dose effect for A/Sichuan. All vaccine doses were well tolerated by both groups. We conclude from our data that higher vaccine doses may result in a better antibody response against some antigens but not against others. Therefore, in general, increasing the vaccine dose is no adequate method to improve the antibody response.
One hundred and fifty-three nursing home residents received 0, 5, 25 or 50 mg
N-acetylglucosaminyl-
N-acetylmuramyl-dipeptide (GMDP) orally, and trivalent influenza subunit vaccine intramuscularly. ...One day after intervention, there was a strong increase of total leucocytes, monocytes and neutrophils in the groups receiving 25 or 50 mg GMDP. A GMDP dose dependent increase in systemic, but not in local, vaccine side-effects was observed. No significant differences in post-vaccination haemagglutination inhibiting serum antibody titres were observed between the four groups, indicating that oral administration of GMDP together with influenza vaccination, does not lead to a higher vaccine efficacy.
Both antibody and cell-mediated immune responses are involved in the defence against influenza. In Wegener's granulomatosis (WG), antibody responses to influenza vaccination appear to be similar to ...those in healthy controls, but cell-mediated responses have not been studied.
To determine whether cell-mediated responses to influenza vaccination in WG vary from those in controls.
Twenty-five patients with WG and healthy controls received subunit influenza vaccine. Peripheral blood mononuclear cells were obtained before and 1 month after vaccination. Cell-mediated responses to A/H1N1 and A/H3N2 were assessed using interferon gamma (IFN gamma) ELISpot and intracellular cytokine staining for IFN gamma, tumour necrosis factor and interleukin 2.
Before vaccination, patients and controls showed similar recall responses to A/H1N1 and A/H3N2. After vaccination, patients and controls showed similar levels of increase in spot-forming cells against A/H1N1 and A/H3N2. By flow cytometry, upon vaccination, proportions of cytokine-producing CD4 T cells increased in patients and controls for A/H1N1 and A/H3N2.
Cell-mediated responses to influenza vaccination in patients with WG are comparable to those in healthy controls.
In 1999, avian influenza A/Hong Kong/1073/99 (H9N2) virus emerged as a pandemic threat to human beings. We aimed to assess safety, tolerability, and antigenicity of whole virus and subunit H9N2 ...vaccines in healthy volunteers.
In a phase I randomised trial we randomly assigned 60 participants to whole virus or subunit H9N2 vaccine. Two doses of 7·5 μg, 15 μg, or 30 μg haemagglutinin influenza A H9N2 vaccine, were given 3 weeks apart. We measured antibody responses by haemagglutination-inhibition and microneutralisation. The primary outcome was geometric mean antibody titre 21 days after vaccination. Analysis was per protocol.
Both vaccines were safe and well tolerated. The antibody titres after vaccination did not differ significantly between subunit and whole virus vaccine. 24 of 60 prevaccination serum samples had unexpected reactivity to H9N2, but only in participants older than 32 years, in whom one dose of either vaccine evoked antibody responses associated with protection. In participants aged 32 years or younger, antibody responses to one dose of whole virus or subunit vaccine were poor, fulfilling none of the criteria used for yearly relicensing of interpandemic vaccines. Whole virus vaccine produced a significantly higher probability of seroconversion compared with subunit virus for this age-group.
In immunologically naive patients whole-virus vaccine produced better responses than subunit vaccine. Two doses of subunit or whole virus vaccine would leave a large proportion of the naive population (⩽32 years) unprotected against A/Hong Kong/1073/99 (H9N2). Primed patients should be protected with a single dose of either vaccine.
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