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Psychosomatic Medicine 66:950-953 (2004)
© 2004 American Psychosomatic Society

ORIGINAL ARTICLES

Psychosocial Factors and the Response to Influenza Vaccination in Older Adults

Jan A. Moynihan, PhD, Mark R. Larson, PhD, John Treanor, MD, Paul R. Duberstein, PhD, Alan Power, MD, Bernard Shore, MD and Robert Ader, PhD

From the Department of Psychiatry and the Center for Psychoneuroimmunology Research (J.A.M., M.R.L., P.R.D., R.A.) and the Department of Medicine and the Vaccine Evaluation Treatment Unit (J.T.), University of Rochester Medical Center, Rochester, New York; St. John’s Home (A.P.) and the Jewish Home (B.S.), Rochester, New York.

Address correspondence and reprint requests to Jan A. Moynihan, PhD, University of Rochester Medical Center, Box PSYCH, 300 Crittenden Blvd., Rochester, NY 14642. E-mail: jan_moynihan{at}urmc.rochester.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
OBJECTIVE: We examined the influence of psychological state (depression, negative affect, perceived stress) and social support on pre- and post-vaccination response to influenza vaccine.

METHODS: Venous blood was drawn from 37 nursing home residents before and following injection of the trivalent influenza vaccine (comprised of the New Caledonia (NC), Hong Kong (HK), and Panama (Pan) strains of flu). The Geriatric Depression Scale, Perceived Stress Scale, Positive and Negative Affect Schedule, and Multidimensional Scale of Perceived Social Support were completed following the initial blood draw.

RESULTS: Social support and perceived stress were correlated with pre-vaccine antibody responses to two of the three vaccine components (HK and NC). Social support was negatively correlated with both pre- and post-vaccine titers to Pan. Depression, positive affect, and negative affect were not related to vaccine response.

CONCLUSIONS: Perceived stress and social support influence the rate of decline of antibody titers to previous exposures to some strains of influenza occurring either naturally or via deliberate vaccination.

Key Words: social support, • perceived stress, • influenza, • vaccination, • elderly.

Abbreviations: ANOVA = analysis of variance;; GDS-15 = Geriatric Depression Scale;; HAI = hemagglutination inhibition;; HK = Hong Kong;; MSPSS = Multidimensional Scale of Perceived Social Support;; NC = New Caledonia;; Pan = Panama;; PANAS = Positive and Negative Affect Schedule;; PSS = Perceived Stress Scale.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Demographic trends underscore the public health significance of research to prevent morbidity and mortality in adults 65 years of age and older. Societal and economic costs of diseases of old age will increase exponentially as the population ages. In 2004, 36 million Americans are over the age of 65 (12.6% of the population); by 2030, it is expected that this number will nearly double to 70.3 million Americans, or 20% of the population (1). Given the public health and policy challenges posed by the aging of the large population born after World War II, research aimed at understanding the myriad influences on health and immune function of middle-aged and older adults is vital. Identifying modifiable risk factors for adverse health outcomes should have a high priority. Development of novel, low-cost interventions aimed at modifying those risk factors could lead to substantial cost-savings, reduce morbidity, and enhance well-being.

Vaccination with trivalent influenza vaccine has been a good model for examining relationships among age, psychosocial characteristics, psychological states, and immune response. Studies comparing vaccine responses in the elderly with those of young adults demonstrate that antibody titer, T cell proliferation and cytokine production are significantly decreased in the elderly compared with young adults (2–4). It has been estimated that influenza vaccine efficacy is approximately 50% in elderly subjects, compared with 70% to 90% of young-middle aged adults (2,3,5,6).

Depression and social support have been shown to affect response to vaccination, perhaps most dramatically in the aged (7–9). Glaser et al. (7) reported that elderly Alzheimer’s caregivers (mean age, 68 years) had an accelerated decline in antibody response to pneumococcal vaccine following immunization than age-matched noncaregivers. No significant difference between the two groups was observed in perceived stress; caregivers did, however, report less social support than noncaregivers. Kiecolt-Glaser et al. documented that caregivers (mean age, 73 years) had a poorer antibody response to influenza vaccination than matched controls (8); in that study, caregivers reported higher levels of depressive symptoms compared with controls. In a similar study, Vedhara et al. (9) reported significantly higher levels of emotional distress in elderly caregivers (median age, 73 years) compared with matched controls, as well as a lower percentage of caregivers with a positive antibody response to flu vaccine.

In the present study, we examined antibody responses pre- and post-vaccination with trivalent influenza vaccine in residents of two local nursing homes. Although our initial hypothesis was that the rise in antibody titer post-vaccination would be correlated with social support, we report that psychological state is a predictor of preexisting antibody titers, rather than post-vaccine titers, to two of the three vaccine components (New Caledonia (NC) and Hong Kong (HK) strains). Finally, a negative association between social support and antibody responses to the Panama (Pan) component was observed.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
The protocol was approved by the Research Subjects Review Board at the University of Rochester Medical Center (RSRB no. 09583).

Subjects were 37 residents of two local nursing homes, either the St. John’s Home (n = 28) or the Jewish Home (n = 9) in Rochester, NY who were over the age of 65, able to give informed consent, and were scheduled to receive the influenza vaccine in the fall of 2002. The trivalent influenza vaccine administered in the 2002 to 2003 flu season included three strains: strain A (H3N2), Panama/2007/99, strain A (H1N1), New Caledonia/20/99-like, and strain B, HongKong/330/2001-like (abbreviated as Pan, NC, and HK component antigens) (10). Influenza vaccination in the previous year was documented for all but two subjects; however, the pre-vaccine titers in these two subjects was consistent with having been vaccinated in 2001.

Women made up the majority of the recruited subjects (n = 27). The mean age of the population was 84 (range, 67–97 years; SD 7.1 years); all subjects were white. Medical records were reviewed to determine eligibility to participate in this study. Nursing home staff identified potential participants who were thought to have sufficient cognitive functioning to be interviewed; patients with obvious dementia were excluded from the study. Patients who were otherwise unable to respond to questionnaires were excluded. Patients with unstable medical conditions or other acute or chronic conditions which, in the opinion of the Medical Directors of the two facilities, would render vaccination unsafe or interfere with an evaluation of the response (i.e., immunosuppressive illness or immunosuppressive medications) were excluded.

Venous blood (approximately 10 ml) was drawn on two occasions: immediately before vaccination and 3 weeks following immunization. Sera were stored at –20°C, and assayed for the presence of hemagglutination-inhibiting antibodies to the three viral strains contained in the vaccine. Influenza vaccine titers were determined by hemagglutination inhibition (HAI) assay (11), using serial two-fold dilutions starting at 1:10 and continuing to 1:2560. Titers were expressed as the log base2 dilution for analysis.

Four questionnaires were administered to subjects between the two blood draws. The Multidimensional Scale of Perceived Social Support (MSPSS) (12) is a well-validated 12-item scale that measures perceived social support divided into three constructs, support derived from family, friends, and significant other. The Geriatric Depression Scale-Short Form (GDS-15) (13) is a 15-item self-report measure of depressive symptoms in the prior week. The scale is widely used in psychogeriatric research and has been recommended as a screening measure for depression in older primary care patients (14). The 20-item Positive and Negative Affect Schedule (PANAS) (15) assesses affective arousal and provides a measure of hedonic well-being. The well-validated PANAS is one of the most commonly used measures of trait and state affect, and research has supported the viability of the measure among the elderly (16). The Perceived Stress Scale (PSS) (17) measures the degree to which current life situations are appraised as stressful. The focus on perceived, rather than "objectively defined," or "life event" stress recognizes that the impact of stressful events is, to a substantial degree, determined by appraisals of event stressfulness (17,18). Interviewers were undergraduate students at the University of Rochester who received training and ongoing supervision.

Data were analyzed using analysis of variance (ANOVA) or Pearson correlation, with p values computed using Fisher’s r to z transformation (StatView, SAS Institute, Cary, NC).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 
Pre- and Post-vaccination Titers to Trivalent Vaccine
As expected, given lifetime exposure to influenza vaccine and/or influenza itself, a preexisting antibody titer to each of the three vaccine components was observed, and a significant increase in titer (p < .001 for each strain) occurred following vaccine challenge (Figure 1). Overall, a two-fold rise in titer to each vaccine component was noted. A four-fold change in titer (typically defined as a positive clinical response) was observed in 45.9% of the sample for the NC strain, 59.5% for the HK strain, and 62.2% for the Pan strain. The two individuals for whom documentation of 2001 vaccination could not be obtained had both pre- and post-vaccination titers to all three components that did not differ from those who were known to have been vaccinated in 2001.



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  		Figure 1. Antibody titers in 37 elderly subjects determined before and 3 weeks after administration of the influenza vaccine (comprised of the HK, NC, and Pan strains of flu). *Significant difference compared with pre-vaccination titer for each strain (p < .001).

 
Both the pre- and post-vaccination titers to the NC strain were significantly lower than the titers to HK and Pan (p < .01). Significant, positive correlations between pre- and post-vaccination titers were observed for each of the three components of the vaccine (Table 1). In addition, the NC pre- and post-vaccine titers were positively correlated with pre- and post-HK titers; the only significant correlation with the Pan strain was between HK post-vaccination and Pan post-vaccination.


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  		TABLE 1. Correlation Matrix for Social Support and Antibody Titer to Trivalent Influenza Vaccine
 
The effects of age, gender, and nursing home on antibody titers both pre- and post-vaccination were examined using correlational analyses (age) or ANOVAs (gender and nursing home facility). No significant effects were observed.

Social Support and Antibody Titers
The MSPSS was used to assess subjects’ perception of social support (from a significant other, family, and friends). Correlations among antibody titers pre- and post-challenge and social support for all 37 subjects are shown in Table 1.

Social support was significantly and positively correlated with the pre-vaccination titers to the NC and HK strains of vaccine and negatively correlated with both pre- and post-vaccine titers to the Pan component.

The PSS was used to measure subjects’ perception of stress (completed questionnaires were obtained from 35 subjects). Perceived stress was negatively correlated with pre-vaccination antibody titers to the NC and HK components of the vaccine (Table 2). No significant correlations with the Pan strain were observed.


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  		TABLE 2. Correlation Matrix for Perceived Stress and Antibody Titers to Trivalent Vaccine
 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
ACKNOWLEDGMENTS
 REFERENCES
 
Previous findings suggest that elderly Alzheimer’s caregivers have a poorer antibody response to influenza vaccination than demographically matched controls, presumably due to the stress of providing care (8,9). Thus, we hypothesized at the outset that, within a population of elderly nursing home residents, those reporting greater perceived stress, negative affect, and depression or lower social support would have lower antibody responses following vaccination. In contrast to those earlier studies, we demonstrated that social support and perceived stress among nursing home residents were correlated with the pre-vaccination (baseline) antibody titers to two of the three components of the flu vaccine, the HK and NC strains. We did not observe significant correlations of antibody titers with depression or positive or negative affect. Our study on nursing home residents, however, cannot be compared directly with those on elderly Alzheimer’s caregivers. The living environments of the two groups were very different, and our sample of elderly volunteers (mean age, 84 years) was older than those reported on by Glaser et al. (7) (mean age, 68 years), Kiecolt-Glaser et al. (8)(mean age, 73 years), and Vedhara et al. (9) (mean age, 73 years).

In hindsight, given the probable past exposure to influenza and influenza vaccination in our elderly volunteers, baseline anti-flu antibody titers to a variety of strains of influenza would be expected, and titers would be expected to decline at varying rates over time. We could hypothesize, then, that psychosocial factors might be correlated with the rate of decline of preexisting antibody titers to the NC and HK strains; high levels of social support, for example, would predict greater long-term maintenance of antibody levels. Interestingly, Glaser et al. (7) had also observed that poorer social support was associated with faster decline in antibody titer to pneumococcal vaccine in Alzheimer’s caregivers. Future studies should target the kinetics of antibody production and decline following vaccination.

Further, it has been observed that baseline antibody titers can be negatively correlated with the magnitude of post-immunization titers (6). Perhaps specific or cross-reacting antibodies to flu may suppress or otherwise impair new antibody production (19,20). Given these observations, it becomes less surprising that we did not observe associations among stress, social support, and post-vaccination titers.

The response to the NC (strain A, type H1N1) and HK (strain B) strains of flu were correlated with each other; thus, it is not surprising that psychosocial factors exerted similar influences on these titers. We observed, however, negative correlations between pre- and post-vaccination titers to Pan (strain A, type H3N2) and social support. We have no tested explanation for why one of the three vaccine components should differ from the other two. It is interesting to note, however, that during the previous influenza season (2001–2002), the overwhelming majority of influenza isolates collected by the Centers for Disease Control from infected individuals in the United States were influenza A viruses (98%). Further, of the type A strains that were subtyped, 98% were antigenically similar to the A/Panama/2007/99 (H3N2) strain (21). Thus, if "natural" exposure occurred throughout the preceding flu season, it is possible that titers to Pan would be differentially affected. This speculation would need to be examined in a future study.

Our data also support the findings that the response to flu vaccine in the elderly is impaired compared with adults under the age of 65. A four-fold change in titer to the vaccine was observed on average for the three vaccine components in 55% of our subjects. This confirms other studies in the literature estimating that a positive response to vaccination occurs in approximately 50% of elderly, compared with 70% to 90% of young-middle aged adults (3,6,22). Protection rates in frail elderly in geriatric medical long-term care have been reported to be as low as 33% (6); our institutionalized elderly subjects may represent a healthier sample. The risk of contracting influenza following immunization is greatest among those elderly demonstrating poor antibody and cell-mediated immune responses (2). Most importantly, it is estimated that 90% of the deaths caused by influenza annually in the United States occurs in those individuals 65 years of age and older (5). Strategies designed to improve rates of seroconversion to influenza vaccine, including interventions targeted at decreasing perceived stress and increasing social support, in the elderly could significantly lessen morbidity and mortality associated with flu.


   ACKNOWLEDGMENTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
REFERENCES
 
The study was funded by PHS grant: N01-A1-25460.

Received for publication April 6, 2004.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 ACKNOWLEDGMENTS
 REFERENCES
 

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