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Comparison of Immune Response to the Influenza Vaccine in Obese and Nonobese Healthcare Workers

Published online by Cambridge University Press:  02 January 2015

Michael A. Sweet,
Jonathan A. McCullers,
Paul R. Lasala,
Frank E. Briggs,
Anne Smithmyer and
Rashida A. Khakoo
Michael A. Sweet*
Affiliation:
Center for Quality Outcomes, West Virginia University Hospitals, Morgantown, West Virginia
Jonathan A. McCullers
Affiliation:
St. Jude Children’s Research Hospital, Memphis, Tennessee
Paul R. Lasala
Affiliation:
West Virginia University Pathology, West Virginia University Hospitals, Morgantown, West Virginia
Frank E. Briggs
Affiliation:
Center for Quality Outcomes, West Virginia University Hospitals, Morgantown, West Virginia
Anne Smithmyer
Affiliation:
Employee Health, West Virginia University Hospitals, Morgantown, West Virginia
Rashida A. Khakoo
Affiliation:
Department of Infectious Diseases, West Virginia University School of Medicine, Morgantown, West Virginia
*
Address correspondence to Michael A. Sweet, PharmD, Center for Quality Outcomes, West Virginia University Hospitals, PO Box 8242, Morgantown, WV 26506-8242 (sweetm@wvuhealthcare.com).
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Abstract

OBJECTIVE

To determine whether there is a difference in antibody titers and functionality after receipt of the influenza vaccine for obese versus nonobese healthcare workers (HCW).

DESIGN

Prospective observational study.

SETTING

Tertiary medical center.

PARTICIPANTS

Healthcare workers.

METHODS

Baseline influenza antibody titers for obese and nonobese HCW were recorded during the hospital’s 2011 annual influenza vaccination day and follow-up antibody titers were measured 4 weeks later. Antibodies were measured using the hemagglutination inhibition assay and functionality was measured using the micro-neutralization method.

RESULTS

Of 200 initial HCWs, 190 completed the study (97 obese and 93 nonobese). Seroprotection after immunization was not significantly different for nonobese compared with obese HCW for each strain (influenza A [H1N1], 99% and 99%; influenza A [H3N2], 100% and 99%; and influenza B, 67% and 71%, respectively)

All geometric mean titers measured by micro-neutralization showed statistically significant increases in activity. In comparison, there was no difference in the 4-fold increase in H1N1 or B titers. There was a significant difference in the 4-fold increase of H3N2 titers between the nonobese and obese HCWs (82/93 [88%] vs 64/97 [66%], P=.003)

In an ad hoc analysis we found that obese HCWs had a statistically greater number of 4-fold decreases in titers with H1N1 and H3N2.

CONCLUSIONS

There was no significant difference in protection from influenza between obese and nonobese HCWs after immunization.

Infect Control Hosp Epidemiol 2014;00(0): 1–5

Information

Type
Original Articles
Information
Infection Control & Hospital Epidemiology , Volume 36 , Issue 3 , March 2015, pp. 249 - 253
Copyright
© 2014 by The Society for Healthcare Epidemiology of America. All rights reserved 

Influenza viruses cause significant but potentially preventable morbidity and mortality. Influenza epidemics were associated with more than 450,000 deaths in the United States in the 10-year span of 1989–1999.Reference Thompson, Shay and Weintraub1 According to the World Health Organization2 it is responsible for 250,000–500,000 mortalities a year globally. Vaccination remains the most effective method for preventing infection.Reference Cox3 During the 2009 influenza A (H1N1) pandemic, there was an observed increased mortality and resource consumption in morbidly obese individuals.4–Reference Van Kerkhove, Vandemaele and Shinde7 In addition, obese individuals are at increased risk for hospitalization during seasonal influenza.Reference Kwong, Campitelli and Rosella8 West Virginia has the second highest rate of adult obesity in the nation, at 32.5%.9 A prior study demonstrated that obesity was a predictor of poor immunogenic response to hepatitis B vaccination.Reference Weber, Rutala and Samsa10

Normal ranges of protection measured by hemagglutination inhibition (HAI) assay are titers of 1:40.Reference Potter and Oxford11 An effective response (seroconversion) to the influenza vaccination is typically defined as a 4-fold increase in antibody titer. Another measure to show effectiveness is the functionality of the antibodies once formed, measured by the micro-neutralization method.

The current study was designed to measure influenza antibody titers before and after vaccination in obese and nonobese healthcare workers (HCW) to determine whether postvaccine titers are in the protective range and to determine the functionality of the antibodies.

Methods

This was a prospective observational study of influenza vaccination response. Obese and nonobese HCWs had a prevaccination serum specimen drawn, received the recommended 2011/2012 influenza vaccine, and had a 4-week follow-up serum specimen drawn to determine HAI antibody response.

This study was performed at West Virginia University Hospitals (Morgantown) during their 2011 annual influenza vaccination campaign.

All HCWs were asked to participate in this study during this time and incentivized with a $35 gift card to complete the study. The only exclusion criterion was receipt of the vaccine by the intranasal route. HCWs were enrolled on a first come, first served basis until 100 workers were enrolled into each of 2 groups consisting of nonobese HCWs with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) less than 30 and obese HCWs with a BMI greater than or equal to 30.

Demographic and health assessment information was obtained through a questionnaire. The data included on this questionnaire were contact number, age, sex, height, weight, previous year vaccinations, history of influenza in the previous year, diabetes, chronic renal failure, malignancy, liver failure, other comorbidities, chronic steroid use, and other immunosuppressive medications. Height, weight, and an arm circumference were measured before blood collection. Prevaccination blood collection was performed and then influenza vaccine was administered. The HCWs were instructed to return 4 weeks after their vaccination for a second blood collection, after which each received a $35 gift card.

HAI and micro-neutralization assays against A/California/7/09 (H1N1), A/Perth/16/09 (H3N2), and B/Brisbane/60/08 were performed on the serum samples collected on days 0 and 28–35 as described. The geometric mean titers (GMT) and geometric mean ratio were calculated in the pre- and postvaccination samples for each cohort. Seroconversion was defined as either a postvaccination rate of at least 1:40 with an undetectable (<1:8) prevaccination titer or at least a 4-fold increase in titer from pre- to postvaccine HAI. Seroprotection rate was defined as the percentage of HCWs with a postvaccination titer of at least 1:40.Reference Carr, Allison and Van De Velde12

The sample size was determined by the primary objective of seroconversion. On the basis of prior studies, using a seroconversion rate of 80% in the general population to show a 10% decrease in seroconversion for obese HCWs needed a sample size of 155 for a power of 80% with an alpha of 0.05. With acknowledgment of the possibility of the lack of retention of some HCWs, 200 total HCWs were enrolled.

HAI antibody titers were described as geometric mean. The Fisher exact test or the χ2 test was used for comparison of HAI antibody titers and categorical variables. Continuous variables were analyzed using the t test.

Results

There was 95% retention of subjects with 190 of the 200 enrolled people completing the study. Regarding the patient characteristics, there was a statistically greater number of diabetics in the obese group (Table 1). Ten HCWs did not complete the study.

TABLE 1

Baseline Clinical Characteristics of Healthcare Workers

Note. All data are number (percentage) unless otherwise indicated. BMI, body mass index (calculated as weight in kilograms divided by height in meters squared).

Pre- and postimmunization titers and the immunogenicity of HCW are shown in Table 2. Before immunization, there were more HCWs with seroprotection in the obese group for all 3 groups, with H1N1 and B being statistically higher. After immunization, postantibody titers were similar and very high in the H1N1 and H3N2. The influenza B postantibody titers were similar and fewer HCWs were protected. Overall, the change in titers measured by the GMT showed increases in all 3 groups with a lower response in the obese. The GMT to H1N1 demonstrated a statistically significant rise for the nonobese (1.64, P=.0007) and obese (1.35, P=.027). There was a statistically significant increase in the GMT to H3N2 for both groups (nonobese, 2.50, P=.0001; and obese, 2.13, P=.0001). There was a statistically significant increase to B in the nonobese (2.14, P=.0001) but not in the obese (1.2, P=.0521). The change in seroprotection between pre- and postimmunization phases for H1N1 was not statistically different for the obese and nonobese groups. There was a statistically significant increase with H3N2 with the nonobese group (83/100 [83%] vs 93/93 [100%], P=.001) but not with the obese group (89/100 [89%] vs 96/97 [99%], P=.5). There was a statistically significant increase with B with the nonobese group (42/100 [42%] vs 61/93 [66%], P=.001) but not with the obese group (67/100 [67%] vs 69/97 [71%], P=.5). Seroconversion was not statistically different between the nonobese and obese groups for H1N1 groups.

TABLE 2

Pre- and Postimmunization Titers and Immunogenicity of Healthcare Workers

Note. BMI, body mass index (calculated as weight in kilograms divided by height in meters squared); GMR, geometric mean ratio; GMT, geometric mean titers; HAI, hemagglutination inhibition; NS, not significant.

Overall, the changes in micro-neutralization titers measured by the GMT all showed statistically significant increases. Comparing the obese and nonobese groups, there was no difference in rates of 4-fold increases in H1N1 or B titers. There was a statistically significant difference in the rate of 4-fold increase in H3N2 titers for nonobese compared with the obese group (88% [82/93] vs 66% [64/97], respectively; P=.003). There was no difference in the percent of sera achieving titer (%>40 post- after immunization) from micro-neutralization methods between the 2 groups (Table 2).

In an ad hoc analysis we found that the obese group, compared with the nonobese group, had a statistically greater number of HCWs who had a 4-fold decrease in titers from before to after immunization with H1N1 and H3N2, as shown in Table 3.

TABLE 3

Comparison of Titers Declining by 4-Fold Postvaccination

Note. BMI, body mass index (calculated as weight in kilograms divided by height in meters squared).

Discussion

From the results of this study, it appears that HCWs in our institution are protected from influenza A (H1N1 and H3N2) at greater than 80% before vaccination and 99% after vaccination regardless of weight. This can be partially attributed to the combined 91% of HCWs who received the vaccine the year before. With these initial high rates it is hard to delineate the response differences between the 2 groups. There was a significant increase in seroprotection in response to influenza B vaccine for nonobese but not obese HCWs, but the higher initial rate of seroprotection of the obese HCWs confounds this observation.

Historically, the seroconversion rates have been in the range of 42% to 62% after the receipt of the influenza A vaccine.Reference Goodwin, Vinoud and Simonsen13 Our rates were lower, but this is attributed to the initially high antibody titer rates, especially to the influenza A H1N1 and H3N2 strains. Seroconversion rates for influenza B have been reported to be between 35% and 58%, compared with our study that showed 27% in the nonobese group and 12% in the obese group.Reference Goodwin, Vinoud and Simonsen13

Coleman and colleaguesReference Coleman, Talbot and Crimin14 presented an abstract that suggested that obesity was not independently associated with a lower post–influenza vaccination seroprotection against the 2008–2009 vaccine components. The authors specifically looked at patients who were 50 years or older with a BMI of 30 or greater (obese) or with a BMI of less than 30 (nonobese). Nonobese patients, compared with obese patients, had a lower baseline GMT to the 3 components (H1N1, 10.4 vs 12.1; H3N2, 15 vs 5.3; and B, 51.8 vs 56.5) and a subsequent higher seroconversion rate (H1N1, 28% vs 28%; H3N2, 62% vs 73%; and B, 28% vs 34%) than our data showed. Of note, they did demonstrate a much lower rate of seroprotection for the influenza A strains but not the influenza B (H1N1, 43% vs 47%; H3N2, 76% vs 82%; and B, 95% vs 94%), compared with our study.

In an ad hoc analysis of the data, an interesting trend emerged with obese HCWs having a significantly higher rate of 4-fold declining titers in the H1N1 and H3N2 groups. This generates many questions—for example, in the obese population what factors are causing this dramatic decrease in antibody titers in some HCWs who already had a titer of at least 40?

Sheridan and colleaguesReference Sheridan, Paich and Handy15 reported that the pre- and postvaccination antibody titers for the 3 vaccine strains studied were not significantly different between the obese and nonobese participants. They did, however, report that there was a significantly higher increase to the influenza B component in obese versus nonobese participants. Interestingly, similar to our results, they reported that there was a difference between the 2 groups at the 12-month follow-up with the obese participants showing a greater number of at least 4-fold decreases in HAI titers.

Conclusion

There were no significant differences between immunity to influenza between obese and nonobese HCWs after immunization. There are some data suggesting the immunization response may be less in some obese HCWs.

Acknowledgments

Financial support. American Society of Health-System Pharmacists Foundation (Fostering Young Investigators Research Grant to M.S.).

Potential conflicts of interest. All authors report no conflicts of interest relevant to this article.

References

REFERENCES

1.Thompson, WW, Shay, DK, Weintraub, E, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 2003;289:179–186.CrossRefGoogle ScholarPubMed
2.World Health Organization. WHO factsheet: influenza (seasonal). Available at: http://www.who.int/mediacentre/factsheets/fs211/en. Published April 2009. Accessed February 15, 2012.Google Scholar
3.Cox, NJ. Influenza. Lancet 1999;354:1277–1282.Google Scholar
4.Prevention and control of influenza with vaccines; recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010. MMWR Morb Mortal Wkly Rep 2010;59:1–47.Google Scholar
5.Diaz, E, Rodriguez, A, Martin-Loeche, I, et al. Impact of obesity in patients infected with 2009 A (H1N1). Chest 2011;139:382–386.Google Scholar
6.Louie, JK, Acousta, M, Samuel, MC, et al. A novel risk factor for a novel virus: obesity and 2009 pandemic influenza A (H1N1). Clin Infect Dis 2011;52:301–312.Google Scholar
7.Van Kerkhove, M, Vandemaele, KA, Shinde, V, et al. Risk factors for severe outcomes following 2009 Influenza A (H1N1) infection: a global pooled analysis. PLoS Med 2011;8:e1001053.Google Scholar
8.Kwong, JC, Campitelli, MA, Rosella, LC. Obesity and respiratory hospitalizations during influenza seasons in Ontario, Canada: a cohort study. Clin Infect Dis 2011;53:413–421.Google Scholar
9. United States Obesity Statistics for 2010. Available at: http://www.cdc.gov/obesity/data/index.html. Accessed February 15, 2012.Google Scholar
10.Weber, DJ, Rutala, WA, Samsa, GP, et al. Obesity as a predictor of poor antibody response to hepatitis B plasma vaccine. JAMA 1985;254:3187–3189.Google Scholar
11.Potter, CW, Oxford, JS. Determinants of immunity to influenza infection in man. Br Med Bull 1979;35:69–75.Google Scholar
12.Carr, S, Allison, KJ, Van De Velde, L-A, et al. Safety and immunogenicity of live attenuated and inactivated influenza vaccines in children with cancer. J Infect Dis 2011;204:1475–1482.CrossRefGoogle ScholarPubMed
13.Goodwin, K, Vinoud, C, Simonsen, L. Antibody response to influenza vaccination in the elderly: a quantitative review. Vaccine 2006;24:1159–1169.Google Scholar
14.Coleman, LA, Talbot, HK, Crimin, K, et al. Effect of body mass index on serologic response to influenza vaccination in older adults. Presented at the Infectious Diseases Society of America 49th Annual Meeting; Boston, MA; October 21, 2011 (Abstract 538).Google Scholar
15.Sheridan, PA, Paich, HA, Handy, J, et al. Obesity is associated with impaired immune response to influenza vaccination in humans. Int J Obes (Lond) 2012;36:1072–1077.Google Scholar
Figure 0

TABLE 1Baseline Clinical Characteristics of Healthcare Workers

Figure 1

TABLE 2Pre- and Postimmunization Titers and Immunogenicity of Healthcare Workers

Figure 2

TABLE 3Comparison of Titers Declining by 4-Fold Postvaccination