Increased immunogenicity of the MF59-adjuvanted influenza vaccine compared to a conventional subunit vaccine in elderly subjects

Three-hundred and eight outpatient elderly subjects ( 65 years) were randomly assigned to receive the MF59-adjuvanted influenza vaccine (FLUAD; n = 204) or a conventional subunit influenza vaccine (AGRIPPAL S1; n = 104) in order to compare the safety and immunogenicity of the two vaccines. Although mild pain at the injection site was reported more frequently by subjects immunised with the adjuvanted vaccine, both vaccines were shown to be safe and well tolerated. The adjuvanted vaccine was more immunogenic as indicated by higher post-immunisation geometric mean titres (GMTs) and by higher proportions of subjects with post-immunisation four fold increases of antibody titres or subjects with 1/160 post-immunisation HI titres. These differences, statistically significant for all three strains after immunisation, indicated that, by addition of the MF59 adjuvant emulsion, conventional subunit influenza antigens acquire an enhanced immunogenicity without any clinically significant increase of their reactogenicity.     

Low prevalence of diphtheria immunity in the population of Florence, Italy

A seroepidemiological study was conducted in 1994 on a representative sample of the population of Florence in order to verify the immunity coverage against diphtheria. Subjects were divided according to sex and age class. Sera from each selected class were at least 1.5/1000 of the residing population. Diphtheria antitoxin was titrated using a quantitative ELISA test. The results show an overall adjusted prevalence of diphtheria immunity ( 0.01 IU/ml) equal to 63.7%. Subjects of younger age classes have good protection levels (85.5% immune under 30 years), while only half individuals aged 50 years have antibody titres . 0.01 IU/ml. Full protection (antibody titre 0.1 IU/ml) was detected only in a very small proportion of those aged 40 years. Our data show (1) how a recrudescence of diphtheria could theoretically take place in older subjects living in Italy, and (2) stress the importance of periodical re-vaccination of adults.     

Relative antigenicity in mice of H1N1, H3N2 and B strains present in inactivated influenza virus vaccines

The results of a study on serum HAI and neutralizing antibodies induced in mice, by whole influenza virus vaccines containing A/Brazil/11/78 (H₁N₁), A/Bangkok/1/79 (H₁N₂) and B/Singapore/222/79 viruses are reported.According to the GMT of HAI, the antigenic potency of the three vaccine strains appear to be different. The A/Brazil/1.1/78 antigen induced the lowest HAI antibody responses and the A/Bangkok/1/79 antigen the greatest. This behaviour, with a few exceptions, was noted regardless of the HA amount (0.08 g 0.4 g, 2 g) of each strain present in the vaccine, the number of doses (one or two), or the kind of preparation (monovalent or trivalent). The data obtained with the neutralization test with vaccines with medium HA content are concordant with previous findings.On the basis of the ratios of the GMT of the neutralizing antibodies to the GMT of the HAI antibodies, it was concluded that the HAI antibodies to A/Bangkok/1/79 antigen possess, on the whole, a neutralizing activity that is higher than that found for the HAI antibodies to A/Brazil/11/78 and B,/Singapore/222/79 strains. For the latter strains, the neutralizing activity increased after the second dose.The observation of the different degrees of antigenicity of the three vaccine strains suggests That, with currently used inactivated influenza virus vaccines containing equivalent amounts of all- three antigens, the dosage should be taken into consideration when the vaccines are used for subjects lacking in previous exposure to vaccine strains.     

Immunogenicity of a recombinant hepatitis B vaccine (Euvax-B) in haemodialysis patients and staff

Hepatitis B vaccine is the most effective strategy for preventing the transmission of hepatitis B virus (HBV) in haemodialysis centers. Nevertheless, lower vaccine responses have been reported in haemodialysis patients as compared with healthy subjects. This study examines the response to Euvax-B in Brazilian haemodialysis patients and staff. A total of 102 eligible patients (n = 42) and staff members (n = 60) consented to be studied. Patients were immunized intramuscularly with four doses of 40 g of Euvax-B vaccine at 0, 1, 2 and 6 months. In staff members, the vaccine was administered in three doses of 20 g at 0, 1, and 6 months. Post-vaccine samples were taken from all subjects 1 month after each dose. The vaccine response was determined by measuring antibody to the hepatitis B surface antigen (anti-HBs) levels using ELISA. Subjects with anti-HBs titres equal to or higher than 10 UI/L were considered immune protected. Of the haemodialysis patients who received four doses of hepatitis B vaccine, 89.5% responded to Euvax-B vaccine. The geometric mean of anti-HBs titres was 322.8 IU/L (95% CI: 317.7–328). Among staff members, 93.3% reached anti-HBs protective titres after the third vaccine dose. The geometric mean of anti-HBs titres was 2209 IU/L (CI: 2198–2219). Age, male gender and body mass index were not associated with vaccine response in either group. This study showed a good immunogenicity response to Euvax-B in haemodialysis patients and staff.     

Antibody response against heterogeneous circulating influenza virus strains elicited by MF59- and non-adjuvanted vaccines during seasons with good or partial matching between vaccine strain and clinical isolates

MF59 is already known to enhance the breadth of antibody response to mismatched influenza seasonal and avian strains. However, little is known on the effect of MF59 on immunogenicity of influenza vaccines when “apparent” good matching between circulating and vaccine strains exists. To this end, we compared the immune response elicited by MF59-adjuvanted or non-adjuvanted subunit vaccine, containing A/California/7/04(H3N2) strain, against circulating viruses isolated between 2004/2005 and 2006/2007 seasons, belonging to different clades. The advantage offered by MF59 in terms of higher immunogenicity, expressed as higher post-vaccination HI titres, is observable also against viruses showing antigenic and molecular pattern undistinguishable from vaccine strain, but it became even more evident as the antigenic and molecular distance between vaccine and circulating strains grew. These data show that seasonal influenza vaccine adjuvanted with MF59 can offer a stronger benefit as compared to non-adjuvanted vaccine in protecting against a broader range of virus strains circulating during the influenza season.     

Herd immunity and herd effect: new insights and definitions

The term herd immunity has been used by various authors to conform to different definitions. Earlier this situation had been identified but not corrected. We propose that it should have precise meaning for which purpose a new definition is offered: the proportion of subjects with immunity in a given population. This definition dissociates herd immunity from the indirect protection observed in the unimmunised segment of a population in which a large proportion is immunised, for which the term herd effect is proposed. It is defined as: the reduction of infection or disease in the unimmunised segment as a result of immunising a proportion of the population. Herd immunity can be measured by testing a sample of the population for the presence of the chosen immune parameter. Herd effect can be measured by quantifying the decline in incidence in the unimmunised segment of a population in which an immunisation programme is instituted. Herd immunity applies to immunisation or infection, human to human transmitted or otherwise. On the other hand, herd effect applies to immunisation or other health interventions which reduce the probability of transmission, confined to infections transmitted human to human, directly or via vector. The induced herd immunity of a given vaccine exhibits geographic variation as it depends upon coverage and efficacy of the vaccine, both of which can vary geographically. Herd effect is determined by herd immunity as well as the force of transmission of the corresponding infection. Clear understanding of these phenomena and their relationships will help improve the design of effective and efficient immunisation programmes aimed at control, elimination or eradication of vaccine preventable infectious diseases.     

Comparison of three different influenza vaccines in institutionalised elderly

The reactogenicity and the humoral immune response to three influenza vaccines were evaluated in a randomised, double-blind trial at nursing homes in north-east Italy in winter 1998-1999. Of the 285 subjects, who completed the follow-up, 93 were administered virosomal vaccine, 99 received MF59-adjuvanted vaccine and 93 had split vaccine. Ten subjects (0.3%) reported local and/or systemic reactions in the first week after immunisation. After 4 weeks, protection rates (> or = 40) were near 100% for the H1N1 and B strain and 76.0% against H3N2. The MF59-adjuvanted vaccine group had higher geometric mean titres than the other two. However, the true clinical benefit of the new adjuvanted vaccine should be further substantiated by comparative protective studies. Our results suggest that immune response to influenza vaccination in institutionalised elderly is satisfactory.     

Possible correlation between low antigenic drift of A(H1N1) influenza viruses and induction of HI antibodies

This study examined whether, during a seven-year period of low A(H1N1) influenza virus antigenic drift (1988–1989 and 1994–1995, winters), humoral antibody response of elderly volunteers to influenza vaccines could suggest a lack of antibody pressure for drift. In all the years studied A/Taiwan/1/86, the A(HIN1) vaccine component, had a low ability to induce protective hemagglutination-inhibiting (HI) antibody titres ( 1:40). However a similar low immunogenicity was found for some of the different A(H3N2) strain variants of influenza virus, co-circulating in the same period and showing a regular extent of antigenic variations.Although our data could be at least in part explained by the type of study population (elderly and repeatedly vaccinated), postepidemic serological studies did not evidence a consistently lower ability in mounting protective immune response in elderly people as compared with younger against the influenza strains studied. Therefore, our present results did not exclude a true low immunogenicity of A/Taiwan and of some A(H3N2) influenza strains, circulating in the winters examined. This suggests that, besides the necessity to evade prior immunity, additional factors could influence the frequency of influenza viruses antigenic drifts.Abbreviation HI hemagglutination inhibiting     

Prevalence of influenza immunisation in Australia and suggestions for future targeting of campaigns

Summary Objectives: Reports on the results of a national survey conducted in Australia, in 2000. The objectives were to determine national estimates of influenza vaccination coverage for each state and territory of Australia, to obtain information related to attitudes towards and influences on immunisation decisions and explain the factors involved with failure to immunise.Method: The survey was conducted using the Computer Assisted Telephone Interview (CATI) system. The overall participation rate for the survey was 88.6% and the final number of completed interviews across Australia was n=10505.Results: Two target groups, those aged 65 years and over and those at risk of influenza aged between 40 and 64 years were defined. The overall immunisation rates in these two groups were 74% and 32% resp. The rate of immunisation among females generally exceeded that of males. A multivariate model provided the best joint set of explanatory variables for not getting immunised. These include sex, income, general practitioner recommendation, and general perceptions regarding the influenza injection.Conclusion: This study identified important issues in the decisions of people to immunise. It also highlighted the need to target the findings in effective immunisation policies and strategies to improve health outcomes for those at risk of adverse influenza events.Population Health Division, Commonwealth Department of Health and Aged Care     

The use of immunosome technology for vaccines against rabies and other viral diseases

Subunit viral vaccines present several advantages. They are free of nucleic acids (of viral and/or cellular origin) and proteins of cellular and/or serum origin; they contain only the relevant antigen.For rabies virus, the antigen which induces the virus-neutralizing antibody (VNAb) is the glycoprotein (GP), which is anchored, in form of spikes, to the viral membrane. The GP may be extracted from the virion but, after solubilization and purification, it appears to be poorly immunogenic. In order to restore its immunogenicity, GP molecules are anchored to preformed liposomes (unilamellar phospholipid vesicles) to mimic their native structure and environment. The subunit vaccine obtained by this technique is called an immunosome (IMS).Rabies immunosomes exhibit structural and immunological properties very similar to those of the viral particle. The rabies glycoprotein molecules, anchored to the lipid bilayer of the liposome, correctly expose the immunodominant epitope involved in VNAb induction and induce a strong specific humoral immune response. They also induce a specific cellular immune response. As a result IMS have a highly protective activity when tested with either pre- or post- exposure potency tests.Immunosome technology may be applied to other purified membrane proteins or amphiphilic peptides to restore their immunogenicity.Presented at the XXII National Congress of the Italian Society for Microbiology, Salsomaggiore 1–4 May, 1988.Corresponding author.     

Dimensionen der Zufriedenheit im Alter

Zusammenfassung In einer Interview-Studie von 480 Betagten in städtischen Verhältnissen wurden neben anderen Fragen auch solche zur Zufriedenheit gestellt. Eine Faktoranalyse der Antworten erlaubt die Unterscheidung eines Faktors Depressivität von einem Faktor Zufriedenheit mit Sozial-kontakten und einer gesundheitlichen Dimension.

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Dimensions of satisfaction among old people

Summary In an interview study of 480 aged persons, questions on satisfaction with several aspects of life were included. A factor analysis allows to distinguish a factor relating to depressivity from a factor satisfaction with social contacts and a health-related dimension.

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Dimensions de la satisfaction des personnes âgées

Résumé Das une enquête d'un échantillon de 480 personnes âgées, des questions concernant leur satisfaction ont été inclues dans l'interview. Une analyse factorielle permet de distinguer un facteur associé à la dépressivité d'un facteur satisfaction avec les contactes sociaux et d'une dimension santé.

     

The adjuvanted influenza vaccines with novel adjuvants: experience with the MF59-adjuvanted vaccine

Elderly people and subjects with underlying chronic diseases are at increased risk for influenza and related complications. Conventional influenza vaccines provide only limited protection in the elderly population. In order to enhance the immune response to influenza vaccines, several adjuvants have been evaluated. Among these, an oil in water adjuvant emulsion containing squalene, MF59, has been combined with subunit influenza antigens and tested in clinical trials in comparison with non-adjuvanted conventional vaccines. Data from a clinical database of over 10000 elderly subjects immunised with this adjuvanted vaccine (Fluad, Chiron Vaccines, Siena, Italy) demonstrate that, although common postimmunisation reactions are more frequent in recipients of the adjuvanted vaccine, this vaccine is well tolerated, also after re-immunisation in subsequent influenza seasons. Immunogenicity analyses demonstrate a consistently higher immune response with statistically significant increases of postimmunisation geometric mean titres, and of seroconversion and seroprotection rates compared to non-adjuvanted subunit and split influenza vaccines, particularly for the A/H3N2 and the B strains. The higher immunogenicity profile of the MF59-adjuvanted vaccine is maintained also after subsequent immunisations. An even higher adjuvant effect was shown in subjects with low pre-immunisation titre and in those affected by chronic underlying diseases. In conclusion, the addition of MF59 to subunit influenza vaccines enhances significantly the immune response in elderly subjects without causing clinically important changes in the safety profile of the influenza vaccine.     

Hard hats vs. soft hearts: The conflict between principles and reality in child and adolescent care and treatment programs

Much of child care in volves quick reactions based on one's automatic pilot derived from how we were parented. This paper is about two seemingly universal automatic pilot systems—the hard hats and the soft hearts. Hard hats are behavior management and modification oriented, while soft hearts are psychodynamically and counselling oriented. Typically, the hard hats tend to have the upper hand due to the nature of our culture, and they therefore have the effect of preventing the contributions of the soft hearts from being realized. That all too frequently sets up a dominant culture and a resentful minority situation. To correct this imbalance, a value orientation from the top which emphasizes mutual respect and utilization is suggested.Grateful acknowledgement is made to Ray Peterson for his helpful suggestions in the preparation of this paper.     

Chronic toxicity and bioaccumulation of 2,5,2′,5′- and 3,4,3′,4′-tetrachlorobiphenyl and Aroclor® 1242 in the amphipodHyalella azteca

The addition of 100 (g/L of Aroclor^® 1242 (A1242) or 2,5,2,5-tetrachlorobiphenyl (TeCB) during 10 week chronic toxicity tests withHyalella azteca resulted in complete mortality. There were no effects on survival, growth, or reproduction after addition of 30 g/L. Toxic effects were observed at tissue levels of between 30 and 180 g/g on a wet weight basis, and tissue levels appear to be a better indicator of toxicity than levels in water. No toxic effects were observed after additions of up to 2,700 g/L of the coplanar congener 3,4,3,4-TeCB.H. azteca has the ability to avoid accumulating in excess of 140 g/g 3,4,3,4-TeCB. The amount taken up was proportional to the amount added in water up to 100 g/L, but was constant at higher additions, possibly accounting for its relatively low toxicity. The low toxicity of the coplanar congener, as compared to the non-coplanar 2,5,2,5-TeCB, is in direct contrast to the high toxicity of coplanar PCB congeners to mammals and may be associated with slower rates of aromatic hydrocarbon metabolism in amphipods. Polychlorinated biphenyl levels measured in amphipods from Lake Ontario are approximately 100-fold below levels associated with toxicity inH. azteca, but are above levels which, through biomagnification up the food chain, lead to salmonid residues in excess of 2 g/g, a tolerance limit for human consumption.     

Response to influenza vaccine in people with non-protective HI antibody titers

The purpose of the study was to determine which factors correlate directly with response to vaccination in such a group of subjects with non-protective HI antibody titers before vaccination. Two vaccines were used, a subunit virus vaccine adjuvanted with MF59 and a split virus vaccine. The analysis indicated that immunization with vaccine adjuvanted with MF59 was an independent variable for immune response against A/H3N2 (OR: 3.51; 95% CI: 1.81–6.79) and B (OR: 2.31; 95% CI: 1.37–3.89). The results suggest that antibody response to vaccine is satisfactory in elderly people previously lacking a protective antibody titer, and that the adjuvanted vaccine reveals a better immunogenicity.     

Oral immunisation of mice with live Japanese encephalitis virus induces a protective immune response

This study was undertaken to evaluate the efficacy of oral immunisation of mice with live Japanese encephalitis virus (JEV). Swiss albino mice were immunised with JEV by the peroral (p.o.), intraperitoneal (i.p.) and the subcutaneous (s.c.) routes on days 0, 7 and 14 using either mouse brain derived immunogen (MBDI) or cell culture derived immunogen (CCDI). Oral immunisation of mice evoked high anti-JEV antibody titres by ELISA (Geometric mean titres of 5065 with CCDI and 8854 with MBDI). Moreover, the orally immunised mice showed 76.7% protection with MBDI and 70% with CCDI against intracerebral challenge with a lethal dose of JEV. This study demonstrates for the first time that oral immunisation of mice with live JEV generates a brisk, protective immune response. The results of this study suggest that oral immunisation with JEV holds promise for the future.     

Employment status and quality of life in patients with chronic obstructive pulmonary disease

Objectives: Recently, the conditions for disability benefits were redefined in several countries, stimulating employees to participate on the labour market as long as reasonably possible. Little is known of labour participation and quality of life (QoL) of employees with chronic diseases. This study examines the associations between employment status and QoL in COPD patients. Additionally, the role of lung function, and work-related symptoms and exposures on QoL were explored. Methods: Secondary analyses were conducted on baseline data from a randomized control trail. Patients were categorized as: paid-workers; voluntary non-paid workers (e.g., early retired, house wives) or disabled for work. QoL was assessed by the Chronic Respiratory Questionnaire (CRQ). Between-group differences in CRQ scores, and associations between work-related symptoms or irritants and CRQ scores were uni- and multivariately analysed. Results: Two hundred and ten patients with COPD were included [mean age 53.9 (SD 6.8) years, FEV₁ %predicted 63.5 (SD 18.5)]. No statistically significant differences in lung function between the employment status subgroups were observed. Multivariable analysis showed that the disabled had lower CRQ scores as compared with paid workers (0.52 point difference, p<0.001). The CRQ scores of voluntary non-paid workers were not significantly different from paid workers. Within the group paid workers, patients with many work-related clinical symptoms and being susceptible to various work-related irritants experienced a lower QoL than patients who had respectively no symptoms, or who were not susceptible to these factors. Conclusions: Patients with COPD who were disabled for work showed equal severity of airflow limitation but worse QoL, as compared with paid workers.     

Effect of aflatoxin B and rubratoxin B on bacteriophage and rabbit cornea cells

Summary Rabbit cornea cells exhibited a sensitivity to 1 g aflatoxin b₁ and 5 g rubratoxin B per ml of growth medium. No changes were observed in the bacteriophages tested in the presence of 25 g aflatoxin b₁ or 100 g rubratoxin B per ml of medium by the plaque-forming unit method or single-step growth curves.     

Antibody responses and HIV-1 viral load in HIV-1-seropositive subjects immunised with either the MF59-adjuvanted influenza vaccine or a conventional non-adjuvanted subunit vaccine during highly active antiretroviral therapy

OBJECTIVE: To study immunological and virological parameters in HIV-1-seropositive adults treated with highly active antiretroviral therapy (HAART) for at least 7 months after immunisation with MF59-adjuvanted (FLUAD, Chiron, Siena, Italy) or with non-adjuvanted (AGRIPPAL, Chiron) trivalent influenza vaccine. DESIGN: Blood samples, collected before and after vaccination, were analysed for the presence of antibodies against the vaccine antigens, for number of CD4+ T lymphocytes and HIV-1 RNA levels. RESULTS: Forty-four volunteers received FLUAD and 40 AGRIPPAL influenza vaccine. Thirty days after vaccination both adjuvanted and non-adjuvanted vaccines induced significant increases of anti-influenza virus antibodies. However, antibody titres found in volunteers receiving adjuvanted vaccine were in general significantly higher when compared with those found in the non-adjuvanted vaccine group. The requirements of the European Commission of influenza vaccine for a non-elderly adult population were always met by recipients of the adjuvanted vaccine, even in those with the lowest CD4+ cell counts (<200 cells/mmc). The subjects receiving the non-adjuvanted vaccine failed to met these requirements. The CD4+ T lymphocytes and plasma HIV-1 RNA levels remained stable in the long term, both in people receiving adjuvanted or non-adjuvanted vaccine. CONCLUSION: MF59-adjuvanted influenza induced a significant higher immune responses as compared with conventional vaccine in HIV-seropositive HAART-treated patients. Both vaccines were safe regarding HIV RNA viral replication and loss of CD4+ T lymphocytes.     

Correlation of haemagglutinin-neuraminidase and fusion protein content with protective antibody response after immunisation with inactivated Newcastle disease vaccines

The correlation between the antigen content of inactivated Newcastle disease (ND) oil emulsion-vaccines and the serological response after immunisation was studied. The haemagglutinin-neuraminidase (HN) and fusion (F) proteins of Newcastle disease virus (NDV) were quantified in 33 inactivated oil-adjuvanted ND vaccines using isopropylmyristate (IPM)-extraction and antigen ELISAs. These commercial vaccines differed in NDV-vaccine strain, the method applied to inactivate the vaccine virus, the vaccine valence and the composition of the oil emulsions. Large differences, up to 100-fold, in the antigen quantities present in different vaccines were found. The NDV-HN content and the NDV-F content of the vaccines both highly correlated with the haemagglutination-inhibiting (HI) antibody titres after immunisation. These correlation's were found over a 10,000-fold range of applied antigen. The antigen content of the oil emulsion-vaccines also highly correlated with virus neutralising antibody titres. The presence of serum HI antibody titres in individual specific pathogens free (SPF)-chickens after immunisation with inactivated ND vaccines was highly indicative for clinical protection against challenge with the virulent NDV-Herts strain. Our results are the first to demonstrate that the protective serological response after immunisation highly correlates with the antigen content of oil-adjuvanted vaccines.