Vaccine 29 (2011) 2515–2518 Contents lists available at ScienceDirect Vaccine journal homepage: www.elsevier.com/locate/vaccine Short communication 17-Estradiol restores antibody responses to an influenza vaccine in a postmenopausal mouse model Doan C. Nguyen a , Feda Masseoud a , Xiuhua Lu b , Franco Scinicariello c , Suryaprakash Sambhara b , Roberta Attanasio a,∗ a Department of Biology, Georgia State University, Atlanta, GA 30302, USA b Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA c Division of Toxicology and Environmental Medicine, Agency for Toxic Substances and Disease Registry, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA article info Article history: Received 21 November 2010 Received in revised form 31 December 2010 Accepted 25 January 2011 Keywords: Estrogen Antibody Influenza Vaccine abstract Post-menopausal women belong to an age group that is highly susceptible to influenza infection and its most serious complications. However, data on the immunogenicity of influenza vaccines in these women is limited. Therefore, the antibody response to influenza vaccination was assessed in a postmenopausal mouse model. An inactivated-detergent-split vaccine from the A/New Caledonia/20/99 (H1N1) influenza virus strain was given to three groups of mice: ovariectomized (OVEX), OVEX with 17-estradiol replacement (OVEX + E2), and sham-OVEX. The OVEX + E2 group produced influenza virus-specific serum antibodies, including neutralizing antibodies, at significantly higher levels (p < 0.001) than did OVEX mice. These levels matched those observed in the sham-OVEX group, indicating that ovariectomy negatively modulates the antibody response to the influenza vaccine, whereas 17-estradiol replacement restores this response to levels observed in intact animals. Our findings suggest that immunogenicity and effi- cacy of influenza vaccines need to be evaluated in postmenopausal women, including women receiving hormone replacement therapy. © 2011 Elsevier Ltd. All rights reserved. 1. Introduction Influenza remains a serious public health problem, which generates heavy burdens by its annual epidemics and sporadic pandemics [1]. In the United States, influenza-associated hospi- talizations increase with increasing age [2]. Co-morbidities and serious complications, including pneumonia, respiratory failure and sepsis, are common in older individuals [3]. Post-menopausal women belong to the age group highly susceptible to these influenza complications. Currently, the most effective method in influenza control and prevention is the use of vaccines [1]. In the elderly, because of poor immune responses due to immunosenes- cence, the rate of immunization failure for influenza vaccines may be as high as 50% [4]. Unlike other infections, such as bacterial infec- tions and sepsis, in which females are more resistant than males [5], women are more susceptible than men to influenza virus infection [6]. Sex hormones are known to modulate the development and function of the immune system [7,8]. As compared to men and ∗ Corresponding author at: Department of Biology, Georgia State University, P.O. Box 4010, Atlanta, GA 30302, USA. Tel.: +1 404 413 5397; fax: +1 404 413 5301. E-mail address: rattanasio@gsu.edu (R. Attanasio). pre-menopausal women, postmenopausal women and women subjected to surgical menopause are more susceptible to some spe- cific disorders, including infectious diseases, and exhibit T and B cell impairment [9]. The use of hormone replacement therapy and estrogen replace- ment therapy in postmenopausal women is associated with retaining or improving both B and T cell immune functions, as well as with partly preventing or restoring some of the immune impairments associated with the post-menopause status [10]. However, the modulatory effect of estrogen on immunity to human recommended vaccines, particularly after menopause, is largely uncharacterized. We hypothesized that estrogen modulates the antibody response to influenza vaccine preparations and tested this hypoth- esis in the present study. 2. Materials and methods 2.1. Mice, bilateral ovariectomy and estrogen deliver Pathogen-free adult (8–12 weeks of age) female BALB/c mice (Charles River Laboratories, Inc., Wilmington, MA), were housed and maintained in a pathogen-free environment on a phytoestrogen-free diet. The animals were divided into three 0264-410X/$ – see front matter © 2011 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2011.01.080