This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Burns, V. E. Articles by Carroll, D. Search for Related Content PubMed PubMed Citation Articles by Burns, V. E. Articles by Carroll, D. Related Collections Immunology Infectious Disease Stress and Coping

Perceived Stress and Psychological Well-Being Are Associated With Antibody Status After Meningitis C Conjugate Vaccination

School of Sport and Exercise Sciences (V.E.B., C.R., D.C.) and Department of Immunology, School of Medicine (M.D.), University of Birmingham, Birmingham, England.

Address reprint requests to: Victoria Burns, School of Sport and Exercise Sciences, University of Birmingham, Birmingham, B15 2TT, England. Email: v.e.burns{at}bham.ac.uk

	ABSTRACT

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION NOTES ACKNOWLEDGMENTS REFERENCES

 
OBJECTIVE: Psychological stress has been associated with reduced immune response to a variety of vaccinations. This study is the first to examine antibody status after vaccination with a conjugate vaccine, in which a polysaccharide antigen is conjugated to a protein to elicit a thymus-dependent antibody response.

METHODS: Sixty undergraduate students, who had received the meningitis C conjugate vaccine before recruitment, attended a single testing session. They provided a blood sample and completed a battery of questionnaires, including the Life Events Scale for Students, Perceived Stress Scale, and General Health Questionnaire (GHQ-28). Both meningitis C–specific antibody titer and the serum bactericidal assay titer to whole meningitis C bacteria were assayed.

RESULTS: High perceived stress, but not life events stress, was associated with low antibody titers. Poor antibody titers were also predicted by relatively low levels of psychological well-being as measured by the GHQ-28. Of the GHQ-28 subscales, anxiety/insomnia and social dysfunction were associated with antibody status. No psychological variables emerged from bivariate analyses as predictive of the adequacy of bactericidal titer.

CONCLUSIONS: This study provides the first evidence that antibody status after a conjugate vaccination may be susceptible to psychological influences.

Key Words: meningitis C conjugate vaccination, • perceived stress, • life events, • psychological well-being, • anxiety, • social dysfunction.

Abbreviations: BMI = body mass index;; ELISA = enzyme-linked immunoassay;; GHQ-28 = General Health Questionnaire (28-item version);; IgG = immunoglobulin G;; IQR = interquartile range;; LESS = Life Events Scale for Students;; OR = odds ratio;; PSS = perceived stress scale;; SBA = serum bactericidal assay.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION NOTES ACKNOWLEDGMENTS REFERENCES

 
Vaccinations provide a useful model for studying psychological influences, such as stress, on the integrated immune response to a specific antigen (1, 2). Although contrary evidence exists (3–6), studies using the hepatitis B vaccine in student populations have reported an association between psychological stress and a reduced likelihood of seroconversion after 1 month (4), a reduced response to a low-dose recombinant DNA vaccine at 7 months (7), and an increased risk, more than a year later, of an inadequate antibody response (8). In addition, students with lower antibody responses have reported higher levels of negative affect (6), and students who underwent an intervention designed to reduce stress exhibited higher antibody responses than control participants (9).

The association between stress and antibody response to influenza vaccinations in the elderly seems to be more robust. In comparisons between spousal caregivers and age-matched control subjects, fewer caregivers achieved a four-fold increase in specific antibody level in response to this trivalent vaccination (10, 11). Only one small unpublished study has investigated response to influenza vaccination in a young, healthy population; when vaccinated at the end of a week of examinations, students reporting more distress had significantly smaller antibody responses to the vaccination 3 weeks later (12). As yet only one study has examined rubella vaccination in this context (13). In adolescent girls previously unexposed to the rubella virus, for whom this vaccination elicited a primary response, those high in internalizing and neuroticism and low in self-esteem had poorer antibody responses 10-weeks after vaccination. This relationship did not exist for those who exhibited antibodies against rubella before vaccination, for whom the antibody response to the vaccination was secondary.

All these vaccinations (ie, hepatitis B, influenza, and rubella) induce a thymus-dependent antibody response. This type of antigen requires an antigen-specific T-helper lymphocyte to give cognate help to the B cell, which enables B-cell proliferation and differentiation to antibody-secreting plasma cells. In contrast, polysaccharide antigens, such as those in the capsule of pneumococci, cannot invoke and do not require this T-cell help to generate an antibody response and, therefore, produce a thymus-independent response. Few studies have investigated the relationship between stress and antibody response to thymus-independent vaccinations. In children beginning kindergarten, ratings of problem behavior, an indirect measure of stress, were not associated with antibody response to pneumococcal vaccine. However, those children who exhibited increases in salivary cortisol, suggestive of greater stress, after starting school had lower antigen-specific antibody levels (14). In a study using a similar design to the caregiver-control model described earlier, current caregivers had reduced antibody titers against pneumococcus when assessed 3 and 6 months after vaccination compared with control subjects; this difference, however, did not emerge at 2 weeks and 1 month after vaccination.

A third type of vaccine is the conjugate vaccine. To improve vaccine efficacy, polysaccharide antigens can be conjugated to a protein molecule, which then induces a thymus-dependent antibody response. Although the mechanisms of response are thymus dependent, the antibody produced is against a polysaccharide antigen. The association between psychological factors and antibody response to a conjugate vaccine has not, to our knowledge, been investigated. In addition, most previous research has relied on a simple antibody titer after vaccination; functional assessment of immune status after vaccination has received little attention. The study reported here examined the association between both antibody titer and the serum bacterial assay (SBA) titer after meningitis C conjugate vaccine and life events stress, perceived stress, and psychological well-being. It was hypothesized that high life events exposure, high perceived stress, and low levels of psychological well-being would be associated with poorer antibody titers and lower SBA titers.

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION NOTES ACKNOWLEDGMENTS REFERENCES

 
Participants
Sixty first-year science undergraduate students (23 men, 37 women) at the University of Birmingham were recruited and tested between October 2000 and March 2001. The mean age was 18.90 (SD = 1.02) years, and mean body mass index (BMI), based on reported height and weight, was 22.22 (SD = 2.09) kg/m². In terms of ethnicity, 56 described themselves as white, one as Asian, two as black, and one as mixed race. All participants had received the standard dose of Meningitec (Wyeth, Havant, UK) meningitis C conjugate vaccine before entry to the study as part of a recently introduced national health program. Participants were asked to indicate how long ago they received their vaccination: 1 to 4 months (N = 14), 5 to 8 months (N = 8), 9 to 12 months (N = 31), or 13 to 16 months (N = 7).

Procedure
At the testing session, participants completed a series of questionnaires measuring life events, perceived stress, psychological status, customary coping strategies, and health behaviors. The questionnaires were automatically scored using a scanning system (Scanning Systems SR-360). They also provided a 7-ml venous blood sample. The blood samples, which were allowed to clot, were centrifuged, and the separated serum was frozen until assayed. The study was approved by the appropriate ethics committee, and all participants provided informed consent.

Questionnaires
Psychological stress.
Participants completed Linden’s (15) Life Events Scale for Students (LESS). This student-specific life events inventory required participants to select those life events that they had experienced in the past 12 months from a list of 36 chosen as likely to be pertinent to a university student population. Each stressful event has a prescribed weighted score appropriate to the severity and potential impact of the event. The most stressful event in the list, death of a parent, attracts a weighting of 100, and other events are scaled accordingly. The weighted scores of all the events checked by the participant were totaled to give an overall life events score. The Perceived Stress Scale (PSS) (16) assesses the degree to which the participants appraised their lives as being stressful during the past month. This provides a more subjective assessment of stress than the life events score. The version used here had 14 items, and total scores could range from 0 to 45. Internal consistency is high (Cronbach’s = 0.75–0.86), and test-retest reliability as high as 0.85 has been reported (16).

Psychological well-being.
The General Health Questionnaire (GHQ-28) (17) is a widely used instrument for detecting psychological distress. The 28 items yield four robust factors with acceptable psychometric properties: somatic symptoms (eg, run down), anxiety/insomnia (eg, lost sleep over worry), social dysfunction (eg, taking longer over things), and severe depression (eg, life not worth living). High internal consistency has been reported with ranging from 0.82 to 0.93; reliability coefficients as high as 0.90 have also been reported (18). Of the three possible scoring methods, the simple Likert-type method (0, 1, 2, 3) was selected because it assesses both symptomatology and intensity (17).

Coping styles and social support.
The Brief COPE (19) was administered to assess customary (ie, trait-like) coping styles. The Brief COPE is based on the original COPE inventory (20), has 28 items, and measures 14 conceptually differentiable coping styles: active coping, planning, positive reframing, acceptance, humor, religion, using emotional support, using instrumental support, self-distraction, denial, venting, substance use, behavioral disengagement, and self-blame. Despite the fact that each coping strategy is measured by only two items, internal consistency is acceptable, with Cronbach’s for the different coping styles ranging from 0.50 to 0.90. Response options for each item varied from 0 ("I don’t do this at all") to 3 ("I do this a lot"). After practice (21), three composite styles of coping were derived from the 14 individual coping styles: active coping, calculated as the sum of scores for active coping, seeking instrumental support, and planning; emotion-focused coping, the sum of the scores for acceptance, positive reframing, and using emotional support; and disengagement, the sum of the scores for self-distraction, denial, and behavioral disengagement. This strategy allowed general styles of coping to be assessed. The Perceived Social Support Scale is a questionnaire addressing perceived support from family, friends, and significant others. A Cronbach’s value of 0.88 has been reported along with a test-retest reliability of 0.85. The 12-item version was used (22). With a Likert scale of 1 to 7 for each item, scores could range from 12 to 84.

Health behaviors.
Health behaviors during the period since participants received the meningitis C conjugate vaccination were assessed using a questionnaire adapted from the Whitehall II study (23). Participants were asked, on average, how much they smoked (0, 1–5, 6–10, 11–20, 21+ cigarettes per day), how much alcohol they drank (0, 1–5, 6–10, 11–20, 21–40, 40+ units¹ per week), and how long they slept (0–3, 4–5, 6–7, 8–9, 10–11, 12+ hours per night). A simple categorical scoring system was used in all cases. For example, if a participant indicated that they slept for 8 to 9 hours per night, they were allocated a score of 3. Participants also reported how much time they spent (0, 1–2, 3–5, 6–8, 9–10, 11+ hours per week) in activities of light, moderate, and vigorous exercise intensity. The category scores (0, 1, 2, 3, 4, 5), derived from the categories above, were multiplied by a weighting of 1, 2, and 3 for light, moderate, and vigorous intensity activity, respectively, and the products were summed to yield a composite exercise score.

Participants also reported, for the period since vaccination, how often (never, less than once a week, once or twice a week, most days, once a day, two or three times a day, four or more times a day) they ate each of a list of foods. A categorical scoring system was again used to assess frequency. From this dietary information, two main measures were derived: scores for fresh fruit and cooked vegetables were summed to give a measure of fruit and vegetable consumption, and scores for chips/fried food, crisps/similar, sweets/chocolate, biscuits/cakes/puddings, full-fat dairy products, and processed meat were summed to provide an index of fat intake.²

Immunological Assays
Serum was assayed at the Public Health Laboratory Service Meningococcal Reference Unit, Withington Hospital, Manchester. Serum Neisseria meningitidis serogroup C polysaccharide-specific immunoglobulin G (IgG) levels were determined quantitatively (in µg/ml), by a standardized enzyme-linked immunosorbent assay (ELISA) (24). The skewed distribution of antibody titers, even after log transformation, precluded treating this variable as continuous for the purposes of analysis. Because there were no precedents for defining clinical adequacy, the antibody titer was subject to a median split, and statistical analysis proceeded on the basis of high and low antibody titers.

An SBA was also undertaken to evaluate the functional activity of antibody produced in response to N. meningitidis serogroup C vaccines. The SBA titer was expressed as the reciprocal serum dilution yielding 50% killing compared with the number of target cells present before incubation with serum and complement (24). Again the distribution of this variable precluded treating it as continuous. For the SBA titer, levels of 128 are considered by clinicians to provide evidence of adequate protection against meningitis C (25). Accordingly, SBA titer was also constructed as a binary variable, comprising protective (128) vs. nonprotective (<128) titers.

Statistical Analysis
Data were analyzed using SPSS for Windows (version 8.0). The dichotomized antibody titer (high vs. low) and SBA titer (protective vs. nonprotective) comprised the two outcome variables. Logistic regression analyses examined whether either measure of antibody status could be predicted from differences in stressful life events, perceived stress, psychological well-being, coping strategies, social support, demographic or circumstantial factors, or differences in health behaviors. The subjective psychological variables (perceived stress, psychological well-being, coping strategies, and social support) may interact with the life events experienced by the participant. Therefore, life events was entered into multivariate logistic regression models with each psychological variable in turn to examine whether it modulated the relationship with either outcome measure. Questionnaire data were available for all participants, although two did not provide their height and weight; data for these participants were therefore eliminated in analyses concerning BMI. p values .05 were considered statistically significant.

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION NOTES ACKNOWLEDGMENTS REFERENCES

 
IgG Antibody Titers and SBA Titer
The median antibody titer was 18.48 (IQR = 52.38) µg/ml. Thirty participants were categorized as having relatively high antibody titers; their median antibody titer was 60.11 (IQR = 115.67) µg/ml. The 30 participants with relatively low antibody titers had a median of 9.28 (IQR = 10.71) µg/ml. For the SBA titer the median for the whole sample was 256.00 (IQR = 984.00). Forty-four (73%) participants had a protective SBA titer (128); the remaining 16 (27%) had lower titers (<128). The median SBA titer for the former group was 512.00 (IQR = 1792.00), whereas for the latter group it was 2.00 (IQR = 6.00). In 2 x 2 chi-square analyses, those who had a high antibody titer were highly likely to have protective SBA titers (²(1) = 12.27, contingency coefficient = 0.41, p < .001). Furthermore, a Spearman’s rank order correlation revealed that antibody titer was significantly associated with SBA titer ((59) = 0.59, p < .001).

Predictors of IgG Antibody Titer and SBA Titer
Psychological stress.
Because scores on many of the psychological variables were not normally distributed, each was subjected to a median split. For each psychological variable, the overall median and the median and IQR of the subsequent dichotomized groups are displayed in Table 1. Whether participants were high or low in life events stress did not predict antibody status (OR = 1.31, 95% CI = 0.47–3.60, p = .61). However, participants with high levels of perceived stress were at significantly increased risk of having a low antibody titer (OR = 4.75, 95% CI = 1.58–14.25, p = .005); 19 (70%) of those with high PSS scores had a low antibody titer, compared with 11 (33%) of those with low PSS scores. In contrast, the adequacy of the SBA titer, a functional measure of vaccine efficacy, was not predicted significantly by either life events stress (OR = 0.71, 95% CI = 0.22–2.25, p = .56) or perceived stress (OR = 2.65, 95% CI = 0.81–8.61, p = .11).

Interactions.
It is possible that there may be an interactive relationship between life events and the more subjective psychological measures. Therefore, each psychological variable was entered in turn in multivariate logistic regression models along with life events to investigate whether this altered their relationship with antibody titer. When controlling for life events stress, the association between perceived stress and antibody status was even stronger (OR = 6.24, 95% CI = 1.70–22.85, p = .006). Similarly, the relationship between antibody status and anxiety/insomnia was also strengthened (OR = 5.31, 95% CI = 1.46–19.35, p = .01). Social dysfunction also remained a significant predictor of antibody titer, but the association was not increased by controlling for life events (OR = 3.00, 95% CI = 1.03–8.76, p = .04). No other variable became a significant predictor when entered in a multivariate logistic regression model with life events. The interactions between life events and perceived stress were investigated further by characterizing participants on the basis of life events (low/high) and perceived stress (low/high). A 4 (low LESS/high PSS, low LESS/low PSS, high LESS/high PSS, high LESS/low PSS) x 2 (high antibody, low antibody) chi-square analysis revealed a significant interaction (²(3) = 7.96, p = .05). These data are displayed in Table 2. Participants who perceived their lives as highly stressful yet had low life events scores were the most likely to have low antibody titers (78%). A significant interaction was also found when analyzed using SBA titer (²(3) = 14.95, p = .002); similarly, participants with high perceived stress and low life events stress were the most likely to have nonprotective SBA titers (78%). The interaction between life events stress and anxiety was also investigated in this way. Chi-square analyses revealed a significant interaction between group (low LESS/high anxiety, low LESS/low anxiety, high LESS/high anxiety, high LESS/low anxiety) and antibody titer (high vs. low) (²(3) = 7.89, p = .05). Again the high anxiety/low life events group had the highest proportion of people with a low antibody titer (86%). However, the interaction between these groups and high vs. low SBA titer only approached significance (²(3) = 4.76, p = .19).

Health behaviors.
It is possible that the relationships between antibody status and perceived stress, anxiety/insomnia, and social dysfunction could be mediated or confounded by changes in health-related behaviors. The self-reported health behavior data are summarized in Table 3. As can be seen, smoking, sleep duration, exercise, fruit and vegetable consumption, and estimated fat intake were not significant predictors of antibody titer. In contrast, and contrary to expectations, higher alcohol consumption was associated with a decreased risk of a low antibody titer. In multivariate logistic regression models, in which alcohol consumption was entered, perceived stress (OR = 4.42, 95% CI = 1.43–13.62, p = .01), anxiety/insomnia (OR = 3.92, 95% CI = 1.29–11.88, p = .02), and social dysfunction (OR = 4.32, 95% CI = 1.32–14.18, p = .02) all remained significant risk factors for a low antibody titer. Because anxiety/insomnia could be confounded by sleep duration, both variables were entered together into a multivariate logistic regression model; the relationship between anxiety/insomnia and antibody titer was strengthened by this correction (OR = 5.38, 95% CI = 1.64–17.71, p = .006). Finally, none of health behavior variables predicted the adequacy of SBA titer.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION NOTES ACKNOWLEDGMENTS REFERENCES

The mechanisms by which state measures of psychological status, such as those used in this study, could influence response to a vaccination received some time ago have yet to be fully elucidated. It is unlikely that acute changes in perceived stress and psychological well-being could have a short-term impact on antigen-specific antibody levels because IgG has a half-life of 3 to 4 weeks (26). Furthermore, the life span of bone marrow plasma cells that secrete the antibody is about a month (27) and much longer in a proportion of marrow plasma cells (28, 29). It is more likely that persistence of adequate levels of specific antibody against thymus-dependent antigens depends on the initial immune response that generates specific memory cells and plasma cells from germinal centers and that the mechanisms by which the size and activity of those antigen-specific clones are maintained long term (30). It seems plausible that state psychological measures are indicative of relatively stable dispositional characteristics; scores on the PSS and the GHQ-28 exhibit substantial stability over time (16, 18). It is reasonable to assume, therefore, that these questionnaires are measuring a general disposition to perceive life as stressful and to suffer psychological distress, a disposition that would have existed at the time of vaccination and in the months and years that followed. What is clear is that the associations between perceived stress and psychological well-being and antibody status in this study were not mediated by differences in demographics, timing of vaccination, health behaviors, social support, or coping strategies.

There was also an interaction between life events and both perceived stress and anxiety/insomnia. Participants who were low in life events stress but high in either perceived stress or anxiety/insomnia had the highest frequency of low antibody titers. Broadly similar outcomes emerged from analyses of the SBA titer, a measure of the functional capacity of the immune system against meningitis C. Although high perceived stress per se was a risk factor for a low antibody titer, high perceived stress in the context of low life events exposure would seem to be particularly detrimental. The combination of high perceived stress and low life events had implications for both the enumerative and functional outcome measures. A possible explanation for these interactions is that participants who reported high perceived stress but were exposed to relatively few stressful life events are most likely to be dispositionally prone to high perceived stress levels. Although high perceived stress in the context of high stressful life event exposure is detrimental, it is perhaps the chronic perception of being under high levels of stress, even when actual life events exposure is low, that may confer additional risk of having a poor antibody status.

The associations between psychological factors and antibody status were more robust for antibody titer than for the SBA titer. The antibody titer was determined by ELISA and measured the amount of IgG specific for the antigens that were contained within the vaccine; IgG specific to any other meningitis C antigens were not counted. In contrast, the SBA assay assessed the capacity of all antibodies contained in a serum sample to kill meningitis bacteria. Although antibodies generated in response to vaccination may be the predominant killing agent, antibodies to other meningitis C antigens induced by previous exposure to this commonly encountered bacterium may also be involved in this process. Despite these differences between what the two assays measure, there was a strong correlation between antibody titer and SBA titer. It is possible that the weaker association between psychosocial factors and functional levels of protective antibody reflects reduced statistical power, due to either a low incidence of participants with SBA titers that were nonprotective or the size of the sample (ie, a generally smaller effect size requiring a larger sample for detection).

Although sample size was modest, it was comparable to the number of participants tested in the vast majority of studies that have reported associations between psychological factors and response to vaccination (4, 6, 7, 9–11, 13, 31). Like these studies, the present study clearly had sufficient power to detect associations between antibody titer and both perceived stress and psychological well-being. It should be conceded that the present study has other potential limitations. The absence of a pre-vaccination measure of antibody status precludes control for previous exposure and representation of response as a fold-increase in antibody titer, as has been customary in influenza studies. Given the possibility of natural exposure to meningitis C bacteria, subsequent studies should assess antibody status before vaccination. However, previous research has revealed low vaccine-specific IgG levels in individuals not previously vaccinated with any meningitis C vaccine (32). The design of this study, taking advantage of a recently introduced national vaccination program, did not control for timing of vaccination; timing was, however, not associated with either antibody titer or SBA titer in this study. This variation in vaccination timing, coupled with the fixed, 1-year assessment period of the LESS, may explain in part the lack of association between life events stress and antibody status. A longitudinal study that controlled vaccine administration and assessed stress and antibody status at multiple time points would allow examination of whether the associations reported here reflect effects on initial antibody response or subsequent deterioration of protection.

Our study provides the first evidence that psychological factors are associated with antibody response to a conjugate vaccine. As such, it expands the number and types of vaccination-induced antibody responses shown to be susceptible to psychological stress. The association between stress and vaccination response has potentially important clinical implications. The meningitis C conjugate vaccine is now routinely given in the United Kingdom to 17- and 18-year-olds before attendance at university; in light of our findings, it may be important to monitor subsequent antibody status, particularly in those reporting high perceived stress and low levels of psychological well-being.

	ACKNOWLEDGMENTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION NOTES ACKNOWLEDGMENTS REFERENCES

 
The authors thank Ray Borrow at the Manchester Public Health Laboratory, Withington Hospital, Manchester, for performing the immunological assays.

	NOTES

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION NOTES ACKNOWLEDGMENTS REFERENCES

 
¹ One unit is the equivalent of half a pint (284 ml) of beer, one standard glass of wine (125 ml), or a single shot of spirits (25 ml).

² British-American dictionary: chips = french fries, crisps = chips, sweets = candies, biscuits = cookies.

³ When treated as continuous variables, perceived stress, anxiety/insomnia, and social dysfunction still predicted antibody status.

Received for publication October 3, 2001.

	REFERENCES

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION NOTES ACKNOWLEDGMENTS REFERENCES

 

1. Vedhara K, Fox JD, Wang ECY. The measurement of stress-related immune dysfunction in psychoneuroimmunology. Neurosci Biobehav Rev 1999; 23: 699–715.[CrossRef][Medline]
2. Cohen S, Miller GE, Rabin BS. Psychological stress and antibody response to immunization: a critical review of the human literature. Psychosom Med 2001; 63: 7–18.[Abstract/Free Full Text]
3. Petry J, Weems LB, Livingstone JN. Relationship of stress, distress and the immunologic response to a recombinant hepatitis B vaccine. J Fam Pract 1991; 32: 481–6.[Medline]
4. Glaser R, Kiecolt-Glaser JK, Bonneau RH, Malarkey W, Kennedy S, Hughes J. Stress-induced modulation of the immune response to recombinant hepatitis B vaccine. Psychosom Med 1992; 54: 22–9.[Abstract/Free Full Text]
5. Jabaaij L, Van Hattum J, Vingerhoets JJM, Oostveen FG, Duivenvoorden HJ, Ballieux RE. Modulation of immune response to rDNA hepatitis B vaccination by psychological stress. J Psychosom Res 1996; 41: 129–37.[CrossRef][Medline]
6. Marsland AL, Cohen S, Rabin BS, Manuck SB. Associations between stress, trait negative affect, acute immune reactivity, and antibody response to hepatitis B injection in healthy young adults. Health Psychol 2001; 20: 4–11.[CrossRef][Medline]
7. Jabaaij L, Grosheide PM, Heijtink RA, Duivenvoorden HJ, Ballieux RE, Vingerhoets AJJM. Influence of perceived psychological stress and distress on antibody response to low dose rDNA hepatitis B vaccine. J Psychosom Res 1993; 37: 361–9.[CrossRef][Medline]
8. Burns VE, Carroll D, Ring C, Harrison LK, Drayson M. Stress, coping, and hepatitis B antibody status. Psychosom Med 2002; 64: 287-93.[Abstract/Free Full Text]
9. Petrie KJ, Booth RJ, Pennebaker JW, Davison KP, Thomas MG. Disclosure of trauma and immune response to a hepatitis B vaccination program. J Consult Clin Psychol 1995; 63: 787–92.[CrossRef][Medline]
10. Kiecolt-Glaser JK, Glaser R, Gravenstein S, Malarkey WB, Sheridan J. Chronic stress alters the immune response to influenza virus vaccine in older adults. Proc Natl Acad Sci U S A 1996; 93: 3043–7.[Abstract/Free Full Text]
11. Vedhara K, Cox NKM, Wilcock GK, Perks P, Hunt M, Anderson S, Lightman ST, Shanks NM. Chronic stress in elderly carers of dementia patients and antibody response to influenza vaccination. Lancet 1999; 353: 627–31.[CrossRef][Medline]
12. Bovbjerg DH, Manne SL, Gross PA. Immune response to influenza vaccine is related to psychological state following exams. Psychosom Med 1990; 52: 222.[Free Full Text]
13. Morag M, Morag A, Reichenberg A, Lerer B, Yirmiya R. Psychological variables as predictors of rubella antibody titers and fatigue—a prospective double blind study. J Psychiatr Res 1999; 33: 389–95.[CrossRef][Medline]
14. Boyce WT, Adams S, Tschann JM, Cohen F, Wara D, Gunnar MR. Adrenocortical and behavioral predictors of immune response to starting school. Pediatr Res 1995; 38: 1009–16.[Medline]
15. Linden W. Development and initial validation of a life event scale for students. Can Counsellor 1984; 18: 106–10.
16. Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav 1983; 24: 385–96.[CrossRef][Medline]
17. Goldberg DP, Hillier VF. A scaled version of the General Health Questionnaire. Psychol Med 1979; 9: 139–45.[Medline]
18. Goldberg DE, Williams P. A user’s guide to the General Health Questionnaire. Berkshire, England: NFER-Nelson; 1988.
19. Carver CS. You want to measure coping but your protocol’s too long: consider the Brief COPE. Int J Behav Med 1997; 4: 92–100.[CrossRef][Medline]
20. Carver CS, Scheier MF, Weintraub JK. Assessing coping strategies: a theoretically based approach. J Pers Soc Psychol 1989; 56: 267–83.[CrossRef][Medline]
21. Goodkin K, Feaster DJ, Tuttle R, Blaney NT, Kumar M, Baum MK, Shapshak P, Fletcher MA. Bereavement is associated with time-dependent decrements in cellular immune function in asymptomatic human immunodeficiency virus type-1 seropositive homosexual men. Clin Diagn Lab Immunol 1996; 3: 109–18.[Abstract]
22. Blumenthal JA, Burg MM, Barefoot J, Williams RB, Haney T, Zimet G. Social support, type A behaviour, and coronary artery disease. Psychosom Med 1987; 49: 331–40.[Abstract/Free Full Text]
23. Marmot MG, Davey Smith G, Stansfeld S, Patel C, North F, Head J, White I, Brunner E, Feeney A. Health inequalities among British civil servants: the Whitehall II study. Lancet 1991; 337: 1387–93.[CrossRef][Medline]
24. Maslanka SE, Gheesling LL, Libutti DE, Donaldson KBJ, Harakeh HS, Dykes JK, Arhin FF, Devi SJN, Frasch CE, Huang JC, Kriz-Kuzemenska P, Lemmon RD, Lorange M, Peeters CCA, Quataert S, Tai JY, Carlone GM. Standardization and a multilaboratory comparison of Neisseria meningitidis serogroup A and C serum bactericidal assays. Clin Diagn Lab Immunol 1997; 4: 156–67.[Abstract]
25. Borrow R, Andrews N, Goldblatt D, Miller E. Serological basis for use of meningococcal serogroup C conjugate vaccines in the United Kingdom: reevaluation of correlates of protection. Infect Immun 2001; 69: 1568–73.[Abstract/Free Full Text]
26. Mankarious S, Lee M, Fischer AS, Pyun KH, Ochs HD, Oxelius VA, Wedgwood RJ. The half lives of IgG subclasses and specific antibodies in patients with primary immunodeficiency who are receiving intravenous immunoglobulin. J Lab Clin Med 1988; 112: 634–40.[Medline]
27. Ho F, Lortan JE, MacLennan IC, Khan M. Distinct short-lived and long-lived antibody-producing cell populations. Eur J Immunol 1986; 16: 1297–301.[Medline]
28. Slifka MK, Antia R, Whitmire JK, Ahmed H. Humoral immunity due to long-lived plasma cells. Immunity 1998; 8: 363–72.[CrossRef][Medline]
29. Manz RA, Lohning M, Cassese G, Thiel A, Radbruch A. Survival of long-lived plasma cells is independent of antigen. Int Immunol 1998; 10: 1703–11.[Abstract/Free Full Text]
30. MacLennan IC, Garcia de Viuesa C, Casamayor-Palleja M. B-cell memory and the persistence of antibody responses. Phil Trans R Soc Lond B 2000; 355: 345–50.[CrossRef][Medline]
31. Glaser R, Sheridan JF, Malarkey W, MacCullum RC, Kiecolt-Glaser JK. Chronic stress modulates the immune response to a pneumococcal pneumonia vaccine. Psychosom Med 2000; 62: 804–7.[Abstract/Free Full Text]
32. Borrow R, Southern J, Andrews N, Peake N, Rahim R, Acuna M, Martin S, Miller E, Kaczmarski E. Comparison of antibody kinetics following meningococcal serogroup C conjugate vaccine between healthy adults previously vaccinated with meningococcal A/C polysaccharide vaccine and vaccine-naive controls. Vaccine 2001; 19: 3043–50.[CrossRef][Medline]

This article has been cited by other articles:

				S. Kern and T. Ziemssen Review: Brain immune communication psychoneuroimmunology of multiple sclerosis Multiple Sclerosis, January 1, 2008; 14(1): 6 - 21. [Abstract] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Burns, V. E. Articles by Carroll, D. Search for Related Content PubMed PubMed Citation Articles by Burns, V. E. Articles by Carroll, D. Related Collections Immunology Infectious Disease Stress and Coping