Progesterone-Based Contraceptives Reduce Adaptive Immune Responses and Protection against Sequential Influenza A Virus Infections

• DOI: 10.1128/jvi.02160-16
• Publication Date: 2017-02-09T01:50:25Z
• Authors: Olivia J. Hall; Raffael Nachbagauer; Meghan S. Vermillion; Ashley L. Fink; Vanessa Phuong; Florian Krammer; Sabra L. Klein
• Keywords: 0301 basic medicine; CD8-Positive T-Lymphocytes; Antibodies, Viral; Antibodies, Neutralizing; Survival Analysis; Contraceptives, Oral, Hormonal; 3. Good health; Placebos; Mice; 03 medical and health sciences; Orthomyxoviridae Infections; Influenza A virus; Animals; Immunologic Factors; Female; Progestins; Lung

In addition to their intended use, progesterone (P4)-based contraceptives promote anti-inflammatory immune responses, yet effects on the outcome of infectious diseases, including influenza A virus (IAV) infection, are rarely evaluated. To evaluate impact responses sequential IAV infections, adult female mice were treated with placebo or one two progestins, P4 levonorgestrel (LNG), and infected a mouse-adapted H1N1 (maH1N1) virus. Treatment LNG reduced morbidity but had no effect pulmonary titers during primary infection compared treatment. serum bronchoalveolar lavage fluid, total anti-IAV IgG IgA virus-neutralizing antibody not hemagglutinin stalk lower in progestin-treated than placebo-treated mice. Females challenged 6 weeks later either an maH1N1 drift variant (maH1N1dv) maH3N2 IAV. The level protection following maH1N1dv was similar among all groups. contrast, challenge maH3N2, progestin treatment survival as well numbers activity H1N1- H3N2-specific memory CD8+ T cells, tissue-resident contrast increased neutralizing antibodies against both viruses those achieved While immunomodulatory properties progestins protected immunologically naive from severe outcomes it made them more susceptible secondary heterologous IAV, despite improving infection. Taken together, differentially regulate depending exposure history.IMPORTANCE hormone-based diseases outside reproductive tract is considered. Using mouse model, we have novel observation that synthetic analog found hormonal contraceptives, levonorgestrel, impacts by modulating decreasing cells. Progestins H3N2 Following virus, experienced greater mortality inflammation This study suggests significantly affect adaptive history.