Nic Masurel

Antibody induction by influenza vaccines in the elderly: a review of the literature

Conflicting results have been reported concerning the association between high age and response to influenza vaccines. Some authors have found a reduced response in aged subjects, others have found no difference or even better results as compared with younger control subjects. Seventeen papers were selected from international literature published in the period 1968-1988 for a review of the anti-haemagglutinin-IgG sero-response following vaccination: among 30 cases in which vaccine components could be studied independently, ten revealed a better immune response in young subjects than in the elderly, four found more favourable results in the elderly, and 16 could not detect any significant between-group-differences, the latter most probably because of a high type-2-error. Nine of these 16 cases tended to favour young subjects. These results were relativated by the finding that each paper had at least one of three methodological limitations: (1) the failure to exclude subjects with illnesses or using drugs influencing the immune system, (2) the failure to exclude subjects with previous vaccinations against influenza, (3) the failure to exclude subjects with high prevaccination antibody titres. The direction of these biases is such that failure to address any one issue will lead to an underestimate of the response of aged subjects. In view of the failure to control these biases, it was not surprising that the papers reviewed presented a heterogeneous picture. Thus, the association between high age per se and response to influenza vaccines, if any, has not yet been established. Suggestions are made for future studies in which admission criteria should control health state and previous exposure to influenza antigens.

Adverse reactions to influenza vaccine in elderly people: randomised double blind placebo controlled trial.

OBJECTIVE--To assess the frequency and type of side effects after influenza vaccination in elderly people. DESIGN--Randomised double blind placebo controlled study. SETTING--15 general practices in the southern Netherlands. SUBJECTS--1806 patients aged 60 or older, of whom 904 received influenza vaccine and 902 placebo. MAIN OUTCOME MEASURES--Adverse reactions reported on postal questionnaire completed four weeks after vaccination. RESULTS--210 (23%) patients given vaccine reported one or more adverse reactions compared with 127 (14%) given placebo. The frequency of local adverse reactions were 17.5% in the vaccine group and 7.3% in the placebo group (p < 0.001). There was no difference in systemic adverse reactions (11% v 9.4%; p = 0.34). In general, men reported fewer side effects than women. CONCLUSION--Only local side effects were more common in vaccinated patients and all side effects were mild.

Immune response to influenza vaccination of elderly people. A randomized double-blind placebo-controlled trial

The objective of this study was to determine the immune response to influenza vaccination in elderly people, using a randomized, double-blind, placebo-controlled trial. Venous blood was taken from 1838 people aged 60 years and older, prior to injection with the influenza vaccine or a placebo. A second blood sample was taken three weeks later. The antibody reaction was measured by comparing the geometric mean titre and the percentage of participants who had a protective antibody titre before and after vaccination and for all sera of each strain. A protective antibody titre was found in 43-68% of those who had received the vaccine, depending on the strain investigated. Patients potentially at risk showed a response similar to the other participants. We conclude that influenza vaccination in elderly people provides a reasonable to good immune response. Research is needed on whether a good immune response decreases the incidence of influenza.

Impairment of the immune response to influenza vaccination in renal transplant recipients by cyclosporine, but not azathioprine.

Influenza vaccination has been strongly recommended for immunosuppressed renal transplant recipients. However, immunosuppression may lead to imparied antibody responses. We studied the antibody response to an inactivated trivalent influenza vaccine in 59 renal transplnat recipients with life-sustaining kidney function: 21 were on cyclosporine and prednisone, 38 on azathioprine and prednisone. Healthy volunteers (n=29) and patients on hemodialysis (n=28) served as controls. Despite comparable renal allograft function, cyclosporine-treated patients had a significantly lower immune response against influenza A viruses than azathioprinetreated patients, whether mean antibody levels, fourfold titer rise, or seroconversion to protective titers was analyzed. No significant differences in antibody responses were found between healthy controls and patients on azathioprine. The patients on hemodialysis showed an impaired response to vaccination. However, in contrast to the cyclosporine-treated patients, booster immunization proved valuable in this group.

Effects of repeated annual influenza vaccination on vaccine sero-response in young and elderly adults

Three cohort studies in adults were performed during the period 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.

DOUBLE-BLIND STUDY OF LEUCOCYTE INTERFERON ADMINISTRATION IN CHRONIC HBsAg-POSITIVE HEPATITIS

In a double-blind study human leucocyte interferon was given for six weeks to 8 of 16 patients with chronic HBsAg-positive hepatitis. In the first week 12 x 10(6) reference units were administered daily, and thereafter the dose was halved every week. During the first two weeks leucopenia was observed in 6 of the 8 interferon-treated patients. Apart from a drop in DNA-polymerase activity in the first week, no effect was found on indices of hepatitis-B-virus infection.

Humoral immune response to influenza vaccination in patients with primary immunoglobulin A nephropathy. An analysis of isotype distribution and size of the influenza-specific antibodies.

Primary IgA nephropathy (IgAN) is characterized by mesangial deposits of IgA1, increased serum IgA1 levels, and circulating immune complexes containing predominantly IgA1. It has previously been found that patients with IgAN have a higher than normal IgA response to vaccination, but the IgA subclasses have not been studied. To investigate whether the IgA hyperresponsiveness is limited to the subclass IgA1, which is involved in the pathogenesis of IgAN, we compared the immune responses of 18 patients with 22 healthy controls after intramuscular vaccination with inactivated influenza virus. Antibody titers were significantly higher (P less than 0.0001) for the IgA1 subclass in patients versus controls, but not for the other isotypes. A substantial portion of the IgA and IgA1 antiinfluenza immune response comprised polymers in both patients and controls. There was no preferential response of polymers in patients. Patients produced significantly more monomeric IgA1 antibodies than controls. These results show that patients with IgAN have a hyperresponsiveness limited to the subclass IgA1 and mainly expressed by an excess of monomers.

Annually repeated influenza vaccination improves humoral responses to several influenza virus strains in healthy elderly

The benefit of annually repeated influenza vaccination on antibody formation is still under debate. In this study the effect of annually repeated influenza vaccination on haemagglutination inhibiting (HI) antibody formation in the elderly is investigated. Between 1990 and 1993 healthy young and elderly, both selected by the SENIEUR protocol, were vaccinated consecutively with commercially available influenza vaccines. The elderly had a lower HI antibody response after one vaccination as compared to the young against the A/Taiwan/1/86 (HINI), B/Yamagata/16/88 and B/Panama/45/90 strains. Annually repeated vaccination did not result in a decrease of the HI antibody titres against the A and B vaccine strains in both age groups. Moreover, the elderly had a significantly higher HI titre against the B strains after the second vaccination as compared to the first, resulting in comparable HI titres for young and elderly. Thus, annually repeated vaccination has a beneficial effect on the antibody titre against influenza virus and can contribute to a better antibody-response in the elderly.

EFFECT OF EPIDEMIC INFLUENZA ON KETOACIDOSIS, PNEUMONIA AND DEATH IN DIABETES MELLITUS : A HOSPITAL REGISTER SURVEY OF 1976-1979 IN THE NETHERLANDS

The influence of epidemic influenza on hospitalizations because of influenza, pneumonia and diabetic acidosis in patients with diabetes mellitus was investigated. Data on the weekly incidence of influenza-like illness were obtained from the Continuous Morbidity Registration and the cumulative data on hospitalizations in short-stay hospitals were obtained from the National Medical Registration. Patients with duodenal ulcer were used as a control population. Epidemic elevations of influenza infections were observed in 1976 and 1978. The estimated relative risk for hospitalization because of influenza infection was 1.1 and 1.0 for the two non-epidemic years 1977 and 1979, respectively. For the epidemic years 1976 and 1978 this risk was calculated to be 5.7 and 6.2, respectively. An increased relative risk was also noted for pneumonia; being 25.6 for both epidemic years. The estimated relative risk of dying during hospitalization rose from 30.9 in 1977 to 91.8 in 1978. The number of hospitalizations for ketoacidosis was 50% higher in 1978 than in the other three years. During the epidemic years, 25.7% of patients hospitalized for pneumonia died, while this percentage was 14.6% in the non-epidemic years (P less than 0.05). Differences in mortality due to diabetic acidosis were similar: 25.4% in epidemic and 14.7% in non-epidemic years (P less than 0.01). During the 1978 epidemic, one out of every 1300 patients with diabetes mellitus was hospitalized because of pneumonia. It is estimated that 1 of every 260 patients with IDDM was hospitalized for diabetic acidosis. It is concluded that patients with diabetes mellitus have indeed a very high influenza-associated morbidity.

Improvement of the immunoglobulin subclass response to influenza vaccine in elderly nursing-home residents by the use of high-dose vaccines

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.