Immune response to influenza vaccine in healthy adults and the elderly: association with nutritional status

The immune response and serum nutritional status of 153 elderly residents of nursing homes (mean age 84.4 years) and 95 health care workers (mean age 36.8 years) were assessed before and after immunization with trivalent split-virus influenza vaccine. Postvaccination titers of hemagglutination inhibition (HAI) antibody to A/H1N1 and B among the elderly were lower than those among workers, but the seroconversion rates (greater than or equal to a four-fold rise) for A/H1N1 and A/H3N2 were unexpectedly higher among the elderly than among workers. However, the difference in the seroconversion rate for either strain between workers and the elderly disappeared after adjusting for the prevaccination HAI titer. Among all subjects, lower age and higher serum concentrations of total protein, albumin, Vitamin E and folate were associated with an intact immune response (postvaccination HAI titers >/=40 for at least one strain). In an age-adjusted analysis limited to the elderly, however, only Vitamin E showed a significant association with the immune response. These results suggested that Vitamin E may play an important role in maintaining the immune response, especially among the elderly.     

Frailty is associated with impairment of vaccine-induced antibody response and increase in post-vaccination influenza infection in community-dwelling older adults

Annual immunization with a trivalent inactivated vaccine (TIV) is considered efficacious for prevention of seasonal influenza in older adults. However, significant controversy exists in the current literature regarding the clinical effectiveness of TIV immunization in this highly heterogeneous population. Frailty is an important geriatric syndrome characterized by decreased physiologic reserve and increased vulnerability to stressors. Using a validated set of frailty criteria, we conducted a prospective observational study to evaluate TIV-induced strain-specific hemagglutination inhibition (HI) antibody titers and post-vaccination rates of influenza-like illness (ILI) and infection in frail and nonfrail older adults. The results indicate that frailty was associated with significant impairment in TIV-induced strain-specific HI titers and increased rates of ILI and laboratory-confirmed influenza infection. These findings suggest that assessing frailty status in the elderly may identify those who are less likely to respond to TIV immunization and be at higher risk for seasonal influenza and its complications.     

Paradoxical response to a novel influenza virus vaccine strain: the effect of prior immunization.

BACKGROUND: repeated influenza immunization does not appear to adversely affect the serum antibody response to new influenza strains. OBJECTIVE: to determine whether the immune response to a new influenza strain was inferior in persons previously vaccinated compared with persons not previously vaccinated. DESIGN: randomized, double-blind clinical trial. SETTING: university affiliated community teaching hospital. PATIENTS: 139 healthy adult men and women, mean age 38 years. INTERVENTION: subjects were vaccinated as part of another study. They received influenza vaccines containing influenza strains A/Texas/36/91 (H1N1), A/Nanchang/933/95 (H3N2) and B/Beijing/184/93. One group received a licensed influenza vaccine while the other group received a similar vaccine except the A/Nanchang strain had a diminished potency. MEASUREMENTS: serum hemagglutination inhibition (HAI) antibody titers were determined prior to vaccination and two weeks afterward. If patients had a low postvaccination titer, they were revaccinated and HAI titers were determined two weeks later. RESULTS: 68 adults received the licensed vaccine and 70 received the subpotent vaccine. The groups were similar with regards to baseline characteristics. Those previously vaccinated had significantly lower postvaccination HAI geometric mean titers (GMTs) for all three vaccine strains (A/Texas--127 vs. 359, p < 0.001, A/Nanchang--31 vs. 93, p < 0.001 and B/Beijing--140 vs. 205, p < 0.05). The percentage of subjects with a presumed protective HAI titer of > or =40 was significantly lower among the previously vaccinated groups only for the new influenza strain, A/Nanchang (55% vs. 80%, p < 0.05). For the other two vaccine strains, the percentage with an HAI titer > or =40 was greater than 90% for both groups. CONCLUSIONS: the decrease in serologic response to influenza vaccine among healthy, young adults who were previously vaccinated appears to be unique for this year's influenza vaccine. Further studies are required to determine the frequency and clinical significance of this phenomenon observed in younger healthy adults, and whether it is a general one. Based on its proven efficacy, influenza vaccine should continue to be given on an annual basis to high risk children and adults and to all those 65 years or older.     

A dose-response evaluation of inactivated influenza vaccine given intranasally and intramuscularly to healthy young adults

Epidemic influenza occurs annually throughout the world and is accompanied by excess morbidity and mortality. Increasing the antigen content and topical administration of vaccine are two strategies being explored to improve the immune responses to trivalent inactivated influenza vaccine (TIV). We conducted a randomized, double-blind, placebo-controlled trial to compare the immunogenicity and reactogenicity of intramuscular (IM), intranasal (IN), or combined IM and IN administration of a contemporary US vaccine formulation at escalating dosage levels in young healthy adults. Two hundred forty three healthy adults between the ages of 18 and 45 years received 15, 30, or 60mcg of trivalent inactivated influenza vaccine by either IN, IM or both routes, 120mcg of vaccine IM, or placebo IN and IM. All dosages and routes of vaccine administration were well-tolerated. A bad taste and mild nasal discomfort were more likely to be reported when influenza vaccine was administered IN, while arm tenderness was more common after IM administration. Significant increases in geometric mean serum antibody titers in both HAI and Nt assays were seen in all of the groups receiving influenza vaccine for all test antigens (Por=32 were higher following delivery of the study vaccines by an IM route than by the IN route, but significant increases in serum antibody were seen after IN vaccination. Nasal IgA antibody responses were more common when vaccine was administered IN; and, when the IN dosage was increased, the primary benefit from IN vaccine over IM vaccine appeared to be greater induction of nasal secretory antibody.     

Immune response to trivalent inactivated influenza vaccine in young and elderly subjects

The antibody response (determined using the single radial haemolysis in gel technique) to inactivated whole-virion trivalent influenza vaccine [A/Leningrad/360/86(H3N2), A/Taiwan/5/87 and B/Ann Arbor/1/86], recommended for the 1987-88 winter season in Italy, in 49 elderly (age greater than or equal to 60 years) subjects was compared with the response in 23 young adult (age less than 60 years) volunteers. The subjects were prevalently healthy and a high percentage of young and old people had been repeatedly immunized against influenza in previous years. No significant differences were detected among age groups; moreover, the immune response measured by seroconversion or by a significant rise in antibody titre was constantly low.     

Moderate exercise improves antibody response to influenza immunization in older adults

Influenza vaccine efficacy is reduced among adults over age 65 and a significant number of vaccinated elderly may remain susceptible to influenza virus infection. The effect of moderate exercise training on the immune response to influenza immunization was evaluated in this study. Twenty-seven adults >or=age 64 were assigned to an exercise group (n= 14) or a control group (n = 13). The subjects exercised at 65-75% heart rate reserve (HRR), 25-30 min, 3 days per week, for 10 months. Controls did not change activity. Subjects were immunized with trivalent influenza vaccine before and after the exercise intervention. After the exercise intervention, exercisers exhibited a greater mean fold increase (MFI) in antibody titer to influenza A/New Caledonia/20/99 (H1N1) and A/Panama/2007/99 (H3N2) than controls, and a greater Granzyme B activity to A/Panama/2007/99 than controls. These findings suggest that exercise may enhance the mean fold increase in antibody titer in response to influenza immunization if the influenza antigen was contained in the previous year's vaccine.     

Vitamin E,vitamin A,and zinc status are not related to serologic response to influenza vaccine in older adults: an observational prospective cohort study

It has been hypothesized that micronutrient levels play a role in the immune response to vaccination; however, population-level research on the association between micronutrient levels and immune response to influenza vaccination is needed. In this study, we hypothesized that decreasing levels of nutrients would be associated with decreased hemagglutination inhibition (HAI) responses to influenza vaccination. Therefore, the purpose of this study was to determine whether serum vitamin A, vitamin E, or zinc levels are associated with influenza vaccine response determined by HAI titer in adults 65 years or older. Participants in this study included 205 community-dwelling adults 65 years or older who resided in Marshfield, WI, USA, from fall 2008 through spring 2009. Participants received trivalent influenza vaccine and donated blood samples before and 21 to 28 days after vaccination. Prevaccination levels of serum retinol, α-tocopherol, and zinc as well as prevaccination and postvaccination HAI titer levels were measured. No participants were vitamin A or vitamin E deficient; 20% had low serum zinc levels (<70 μg/dL). Continuous variables and categorical quartiles coding for vitamin A, vitamin E, and zinc levels were not related to prevaccination or postvaccination seroprotection or seroconversion for any of the vaccine components (influenza A [H1N1], A [H3N2], or B), after adjusting for age, sex, body mass index, and prevaccination HAI geometric mean titer. In conclusion, our study population showed no association between variations in levels of serum vitamin A, vitamin E, or zinc and influenza vaccine response as measured by HAI in adults older than 65 years. Thus, associations between micronutrients and other measures of vaccine response, such as cell-mediated immune parameters, should also be explored.     

Antibody and Th1-type cell-mediated immune responses in elderly and young adults immunized with the standard or a high dose influenza vaccine

A comparative analysis of antibody and cell-mediated immune responses was performed in ambulatory medically stable elderly and young adults who received the standard-dose of trivalent inactivated influenza vaccine, containing 15 μg of hemagglutinin (HA) per virus strain, or a high-dose vaccine containing 60 μg HA per virus strain. Among the elderly, the high dose vaccine induced greater HAI (hemagglutination inhibition) and virus neutralization antibody titers than the standard dose vaccine. These responses, however, did not achieve the magnitude of those induced by the standard dose vaccine in young adults. Vaccine-specific circulating T cells producing IFN-γ were detected in the elderly and young adults following immunization. However, there were no significant differences in the IFN-γ responses among groups. On the other hand, the standard dose vaccine in the elderly resulted in the highest proportion of complete non-responders who failed to elicit either an HAI or an IFN-γ response. This study provides further evidence that a higher dose vaccine for the elderly may result in enhanced immune responses which are predicted to improve protection although still of lower magnitude than those induced in younger healthier individuals.     

An influenza A/H3 outbreak during the 2004/2005 winter in elderly vaccinated people living in a nursing home

This study examined the antibody response against the three vaccine antigens and the epidemic A/H3N2 drift variant (A/California) and the prevention of laboratory diagnosed influenza infections in a group of elderly institutionalized people vaccinated with the 2004/2005 influenza vaccine. Antibody titres were measured by hemagglutination inhibition (HI) in sera collected before and 1 month after vaccination. Laboratory diagnosis was done examining throat swabs (RT-PCR or MDCK cell culture) or by serology (seroconversion comparing HI titres in sera collected 1 and 5 months after vaccination). Results obtained showed that influenza vaccination induced an adequate immune response against the three vaccine antigens and the epidemic A/H3N2 variant, however it was not capable of preventing an influenza outbreak due to the new A/H3N2 (A/California) variant.     

Immune response to inactivated influenza virus vaccine: antibody reactivity with epidemic influenza B viruses of two highly distinct evolutionary lineages.

Vaccination of adults (healthy female employees potentially capable of transmitting influenza to high-risk persons; n = 104) in autumn 1990 with a trivalent influenza virus vaccine containing B/Yamagata/16/88 induced a low antibody response to B/Finland/150/90, a recent variant of B/Victoria/2/87-like viruses, as compared with the antibody response to B/Finland/172/91, a current variant in the lineage of B/Yamagata/16/88-like viruses. Up to the end of the epidemic season, the antibody status declined but was still significantly better than before the vaccination. The results suggest that the vaccine strain was appropriate for the outbreak of 1990 to 1991 in Finland, but may provide unsatisfactory protection against B/Victoria/2/87-like viruses. Evidence is given that use of Madin-Darby canine kidney (MDCK)-grown virus as an antigen in the haemagglutination inhibition test (HI) may provide more reliable information about the protective antibodies than use of untreated or ether-treated egg-grown viruses. Significantly higher postvaccination and postepidemic antibody titres were recorded among subjects who exhibited the antibody before vaccination than among seronegative subjects. A significantly higher response rate among initially seronegative people than among seropositive people was recorded for antibody to B/Finland/150/90, but no clear evidence was obtained that the pre-existing antibody could have had a negative effect on the antibody production.     

Neutralizing antibody but not hemagglutination antibody provides accurate evaluation for protective immune response to H5N1 avian influenza virus in vaccinated rabbits

In order to develop an animal model and an assay method to evaluate protective immune response to H5N1 avian influenza vaccination, H5N1 avian influenza vaccine was prepared. New Zealand rabbits were assigned to receive two doses of vaccine with different hemagglutinin (HA) dosage. The sera from vaccinated rabbits was evaluated to determine antibody titer and specificity using different tested methods including hemagglutination inhibition assay (HI), neutralizing assay (NT), cross-HI assay, cross-single immunodiffusion assay and cross-neutralization assay. The titer of HI antibody from rabbits immunized with different doses of HA were no less than 1:40 among groups 14 days after the first immunization. Whereas the NT antibody titer was less than 1:10 among groups 14 days after the first immunization. NT antibodies can be detected 14 days after the second immunization in rabbits immunized at HA doses higher than 6 μg, and the NT antibody titers were equal to or higher than 1:40. A good concentration-dependent NT antibody response can be detected in the vaccinated rabbits 14 days after the second immunization, and in contrast, no concentration-dependent relationship can be seen for HA antibody. The cross-HI test showed sera from vaccinated rabbits could cross react with influenza A H5N1 virus with the titers higher than 1:40. No cross reaction among different types (influenza A/H1N1 virus, influenza A/H3N2 virus, influenza B virus and influenza A/H5N1 virus) can be detected in the sera using the single immunodiffusion assay and using NT antibody test. This showed NT antibody test was demonstrated as a more accurate assay method for evaluating vaccination and quality of the vaccine than HI antibody test.     

Immune response to influenza vaccination in community-dwelling Chinese elderly persons

We investigated the immune antibody response to influenza vaccine in community-dwelling Chinese elderly persons in Hong Kong. One hundred and twenty-eight subjects were recruited in a single-blind, randomized, and placebo-controlled trial. There was no significant baseline difference between the vaccine and placebo groups regarding the seroprotection rates (PR) (haemagglutination inhibition [HI] titre>or=1:40) and geometric mean titres (GMT) of the HI antibody titers. The PR, GMTs and serological response rates increased significantly in the vaccinated versus placebo groups in A-H1N1 at both weeks 4 and month 6. The GMTs and serological response rates but not the PR for A-H3N2 and influenza B increased significantly in vaccinated versus placebo group at week 4 and month 6 post-vaccination. Multivariate logistic regression analyses of the seroconversion rate for A-H3N2 within the vaccinated group showed that gender, coronary heart disease and the serum albumin level were significant predictors (p=0.018, 0.009 and 0.025, respectively). Influenza vaccination provoked a protective HI antibody response in community-living Chinese elderly persons. The mean number of unplanned hospital admissions per subject over 6 months was significantly lower in the vaccinated than in the placebo groups. Hospitalized elderly persons had poorer nutrition, 4-week post-immunization HI antibody titres and lower mini-mental state examination (MMSE) score than non-hospitalized elderly persons. Logistic regression analyses showed that chronic obstructive airway disease significantly increased the risk of hospitalization while the serum albumin level and 4-week A-H3N2 PR (HI>or=40) were independent predictors of a decreased risk of hospitalizations.     

Immune response to split-product influenza vaccine in preterm and full-term young children.

Humoral and cellular immune responses to two doses of influenza antigens were measured in children 6-48 months of age. These vaccinees comprised a previously unimmunized cohort of 18 healthy full-term children and 15 sick preterm children with bronchopulmonary dysplasia and an additional 30 ex-preterm children who were reimmunized. Half of the reimmunized cohort were recovered from bronchopulmonary dysplasia and half had active bronchopulmonary dysplasia. Antibody response was measured by haemagglutination inhibition (HI) and ELISA, and cellular immunity was measured by enumerating memory T cells. Six weeks after immunization, ELISA antibody levels were significantly higher in previously unimmunized full-term vaccinees than in previously unimmunized sick preterm infants (p less than 0.002). No difference was found between sick and recovered reimmunized children. By HI testing greater than 90% of children in both cohorts developed titres greater than or equal to 1:32, and these were generally maintained for at least 20 weeks. T-cell proliferative responses to influenza antigen were greater in the full-term children than in the preterm children (p less than 0.02), irrespective of state of health or prior immunization status. Split-product vaccine was immunogenic in all the cohorts studied; however, factors such as prematurity, health status and previous influenza immunization played important roles in the magnitude of some responses.     

Effect of sublingual administration of interferon-alpha on the immune response to influenza vaccination in institutionalized elderly individuals

A randomized double-blind placebo-controlled study was conducted to determine the effect of sublingual administration of IFNalpha on the immune response to influenza vaccination in elderly institutionalized individuals. Sublingual administration of 10 million IU of IFNalpha immediately prior to vaccination, reduced the geometric mean haemagglutination inhibitory (HAI) and IgG2 circulating antibody titers, and the secretory IgA (sIgA) response in saliva, to the New York strain of influenza A virus, 21 days post-vaccination, without detectable drug-related local or systemic toxicity. IFN treatment did not inhibit the immune response to the other components of the vaccine; the New Caledonia strain of influenza A virus, or the Jiangsu strain of influenza B virus. At the dose tested sublingual administration of IFNalpha reduces the immune response to influenza vaccination in elderly institutionalized individuals.     

Immune response to influenza vaccination in a large healthy elderly population

Elderly individuals not only demonstrate a greater risk of morbidity and mortality from influenza than the young, but also have greater difficulty mounting a protective response to influenza vaccine. The mechanism of the decreased efficacy of influenza vaccination in the elderly is not well understood. The present study was designed to assess the interaction between cell-mediated and humoral immune responses to influenza vaccine in a large population (n = 233) of healthy elderly individuals (mean age = 80.7) living in six continuing care retirement communities (CCRCs). While influenza vaccination resulted in significant increases in the mean anti-influenza antibody titres and mean proliferative responses of peripheral blood mononuclear cells to purified subvirion trivalent influenza vaccine one month after vaccination, only 48.9% and 30.0% of subjects had intact humoral and cell-mediated immune responses, respectively. No association was observed between intact cell-mediated and humoral responses: 14.7% of subjects had an intact cell-mediated, but not humoral response, and 32.6% of subjects had an intact humoral, but not cell-mediated response. However, IFNgamma production was significantly correlated with both antibody and cell-mediated responses to influenza vaccination, a finding not previously reported in the elderly. These results indicate that there is considerable heterogeneity among immune responses of the elderly to influenza vaccination. This heterogeneity needs to be a major consideration in evaluation of new vaccine preparations.     

Local and systemic immune response in nursing-home elderly following intranasal or intramuscular immunization with inactivated influenza vaccine

Intramuscular (IM) influenza vaccines are only 30-40% effective in preventing clinical illness among the elderly, and their effectiveness in eliciting mucosal response may be even lower. The aim of the present study was to evaluate the immunological effect of a novel inactivated intranasal (IN) trivalent whole influenza virus vaccine among nursing-home elderly. Twenty-one institutionalized elderly subjects were vaccinated IN with an inactivated novel vaccine, twice, 21 days apart, and with no adverse effects. Twenty-two subjects were vaccinated once with a commercial IM vaccine. Viral strains used in the 1998/9 vaccine (20 microg of each per dose) were A/Beijing/262/95, A/Sydney/5/97 and B/Harbin/7/94. Serum antibodies (IgG and IgM) and nasal IgA were determined by the hemagglutination inhibition (HI) test and enzyme-linked immunosorbent assay (ELISA), respectively. Mucosal antibody response to the three vaccine strains was detected in 47.6-71.4% and 18.1-31.8% of IN and IM immunized subjects, respectively. Serum antibody response to the three antigens tested was detected in 20.0-61.9% and 18.2-72.7% of IN and IM immunized subjects, respectively. Seroconversion was not significantly different after IN or IM vaccination for both A/Sydney and B/Harbin, but higher for A/Beijing following IM vaccination. On study completion, 57.1, 65.0 and 50.0% of IN vaccinees were seroprotected to A/Beijing, A/Sydney and B/Harbin, respectively. Similarly, 68.1, 77.2 and 54.5% were immune after IM vaccination. The IN vaccine tested was significantly more effective than the IM vaccine in inducing mucosal IgA response. This may prevent influenza at its early stages and thus contribute to the reduction of morbidity and complications in nursing-home elderly.     

Failure of dietary zinc supplementation to improve the antibody response to influenza vaccine

The effect of administering zinc gluconate on the immune response of elderly subjects to influenza vaccine was studied. Sixty health men and women aged 64 to 90 years (mean=74) were randomly assigned to two groups and asked to discontinue all mineral and vitamin supplements for a period of one month. Members of each group were then started on either 50 mg of elemental zinc as zinc gluconate or an identical appearing and tasting placebo in a double blinded manner for one month. Blood samples were then obtained to determine serum zinc and copper levels, and antibody titers to A/Philippines, A/Chile, B/USSR, B/Ann Arbor strains of influenza virus. All individuals were then immunized using trivalent influenza vaccine (Fluogen, Park-Davis), and continued on either zinc or placebo for one month. A second blood sample was then obtained and similarly analyzed. Serum zinc levels increased in both groups, however in the group receiving zinc gluconate supplementation there was a 5.8-fold greater increase than in the control group (p<0.001). There was no significant difference in the immune response in the zinc treated group as compared to the placebo group. This study suggests that elevating serum zinc levels in healthy elderly subjects does not enhance the immune response to influenza vaccine.     

Humoral and cell-mediated immune responses of humans to inactivated influenza vaccine with or without QS21 adjuvant

To evaluate humoral (antibody) and cell mediated immune (CMI) responses, 30 healthy young adults were either given inactivated influenza vaccine with or without QS21 adjuvant. Vaccination site pain and postvaccination myalgias were greater in the QS21 group. Serum antibody increases occurred in 73-93% of subjects for each vaccine and antigen at 2 weeks and 4 weeks but frequencies and mean titers for the two vaccines were not different. No differences in T cell cytotoxicity were detected for either vaccine for influenza A or B infected cells. IFN-gamma for both vaccine groups was increased in supernates after 3 days but not 7 days of stimulation in the cytotoxicity tests; amounts for the two vaccines were similar. To further evaluate CMI, remaining PBMCs were stimulated overnight with cells infected with each vaccine strain; an increase in spot forming cells (sfc) for Granzyme B and IFN-gamma was found for all subjects and in 51 of 54 sfc tests. A slightly higher response in the Gran B test for QS21 subjects was suggested, but no clear immune response advantage was identified among healthy adults for QS21 adjuvanted influenza vaccine.     

Decreased antibody response among nursing home residents who received recalled influenza vaccine and results of revaccination, 1996-97

In November 1996, 11 lots of one U.S. manufacturer's 1996-97 trivalent influenza vaccine were voluntarily recalled because of decreasing potency of the A/Nanchang/933/95 (H3N2) component. Because the elderly are at high risk of developing influenza-related complications, we assessed the postvaccination antibody titers of nursing home residents who received recalled vaccine and assessed the antibody response to revaccination. Blood samples were collected 3 weeks after vaccination from 86 residents at three nursing homes who received recalled vaccine and 86 residents at three other nursing homes who received a different manufacturer's vaccine. Medical records were reviewed. Residents of one nursing home were later revaccinated. Blood samples were collected on the day of revaccination and again in 3 weeks. Serum was tested by hemagglutination inhibition for antibody to all three components of the 1996-97 influenza vaccine. The geometric mean antibody titer (GMT) (33 vs 55; p=0.01) and the percentage of residents with an antibody titer > or = 1:40 (52 vs 67%; p=0.04) to the A/Nanchang/933/95 component were lower among residents who received recalled vaccine compared to those who received non-recalled vaccine, but had similar GMTs against the other two vaccine components. After revaccination, the GMT to A/Nanchang/933/95 increased from 24 on the day of revaccination to 39 (p=0.01) in residents from one nursing home. Therefore, vaccination with the recalled vaccine was associated with lower postvaccination antibody titers to A/Nanchang/933/95, but not against the other two vaccine components. Revaccination was moderately effective in increasing antibody titers. With annual changes in influenza vaccine strains, routine post-release stability testing of influenza vaccine should continue.     

Immunogenicity and efficacy of Russian live attenuated and US inactivated influenza vaccines used alone and in combination in nursing home residents

The immunogenicity and efficacy of Russian live attenuated and US inactivated trivalent influenza vaccines administered alone or in three different combinations were evaluated in a randomized, placebo-controlled, double-blinded study of 614 elderly or chronically ill nursing home residents in St. Petersburg, Russia during the 1996-97 influenza season. Postvaccination serum antibody responses were more frequent among individuals administered the combination vaccines than among those vaccinated with live or inactivated vaccine alone. Only individuals who received live vaccine, alone or in combination with inactivated vaccine, achieved significant postvaccination increases in virus-specific nasal IgA. Efficacy in preventing laboratory-confirmed influenza in vaccinated versus nonvaccinated individuals was 67% (95%CI, 36-81%) for recipients of a combination of the vaccines compared with 51% (95%CI, -17-79%) for recipients of live vaccine alone and 50% (95%CI, -26-80%) for recipients of inactivated vaccine alone. These results suggest that administration of a combination of influenza vaccines may provide a strategy for improved influenza vaccination of elderly people.