|Department Affiliations||Molecular Microbiology and Immunology, Biochemistry and Molecular Biology|
|SOM Address||W2118 Bloomberg School of Public Health Building|
The primary focus of my independent research program is to determine the mechanisms that underlie sex differences in the outcome of viral infections and vaccination. Working with cell culture systems, small animal models, and most recently human clinical samples, we are uncovering the cellular and molecular pathways that differ between the sexes following infection as well as vaccination. Working predominately with influenza virus infection and vaccination, our small animal work is collectively demonstrating that: 1) females of reproductive ages suffer a worse outcome from influenza virus infection than males, a pattern that is reversed in older age; 2) females develop higher inflammatory immune responses during influenza infection than males; 3) following vaccination, females develop higher antibody responses and are better protected against influenza virus challenge than males; 4) exogenous treatment of females with physiological levels of estrogens or progesterone protect females against influenza, primarily by modifying the activity of neutrophils and T cells; and 5) exogenous treatment of either young or old males with testosterone protects against influenza by modifying signaling pathways in T cells. These observation are currently being expanded to human respiratory epithelial cells (i.e., the primary cell type infected by influenza viruses) isolated from men or women, which show sex-specific patterns of activation and chemokine production following infection with influenza viruses. Working with clinicians through the Johns Hopkins Center of Excellence in Influenza Research and Surveillance, we are identifying the correlates of protection following influenza vaccination and how these factors differ between the sexes in elderly populations.
I have over 80 peer-reviewed, have authored several book chapters and edited two book broadly pertaining to sex differences in the outcome of infection and vaccination. My research has been supported by grants from the National Institute of Allergy and Infectious Diseases, the National Science Foundation, and the National Foundation for Infectious Diseases. The body of my research on sex differences and the effects of sex steroids on responses to infection and vaccination as well as my commitment to mentoring were recognized in 2010 when I received the national Society for Women’s Health Medtronic Award. Since my appointment to Assistant Professor in 2006, I have mentored 8 Master’s students, 5 PhD students, and 2 postdoctoral fellows. Since 2006, I have published 41 peer-reviewed manuscripts, 51.2% (21/41) of which were first authored by trainees in my laboratory. I am highly committed to the education and training of students and fellows.
- Klein SL, Jedlicka A, Pekosz A. The Xs and Y of immune responses to viral vaccines. Lancet Infect Dis. 2010 May;10(5):338-49. Review. Erratum in: Lancet Infect Dis. 2010 Nov;10(11):740. PMID:20417416
- Robinson DP, Lorenzo ME, Jian W, Klein SL. Elevated 17β-estradiol protects females from influenza A virus pathogenesis by suppressing inflammatory responses. PLoS Pathog. 2011 Jul;7(7):e1002149. Epub 2011 Jul 28. PMID:21829352
- Lorenzo ME, Hodgson A, Robinson DP, Kaplan JB, Pekosz A, Klein SL. Antibody responses and cross protection against lethal influenza A viruses differ between the sexes in C57BL/6 mice. Vaccine. 2011 Nov 15;29(49):9246-55. Epub 2011 Oct 6. PMID:21983155
- Robinson DP, Hall OJ, Nilles TL, Bream JH, Klein SL. 17β-estradiol protects females against influenza by recruiting neutrophils and increasing virus-specific CD8 T cell responses in the lungs. J Virol. 2014 May;88(9):4711-20. Epub 2014 Feb 12. PMID:24522912
- Fink AL, Klein SL. Sex and Gender Impact Immune Responses to Vaccines Among the Elderly. Physiology (Bethesda). 2015 Nov;30(6):408-16. 2015. Review.PMID:26525340
- Klein SL, Pekosz A. Sex-based biology and the rational design of influenza vaccination strategies. J Infect Dis. 2014 Jul 15;209 Suppl 3:S114-9. Review. PMID:24966191