Influenza virus suppresses the adaptive immune response leaving immune hosts vulnerable to influenza and other respiratory pathogens

• Published in: The Journal of immunology (1950) Vol. 204; no. 1_Supplement; pp. 93 - 93.24
• Main Authors: Bohannon, Caitlin D, Ende, Zachary, Cao, Weiping, Mboko, Wadzanai, Ranjan, Priya, Kumar, Amrita, Mishina, Margarita, Amoah, Samuel, Gangappa, Shivaprakash, Mittal, Suresh K, Garcia-Sastre, Adolfo, Pfeifer, Blaine, Davidson, Bruce A, Knight, Paul, Sambhara, Suryaprakash
• Format: Journal Article
• Language: English
• Published: 01-05-2020
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.204.Supp.93.24

Abstract
Influenza infections are associated with several million cases of severe respiratory illness, hospitalizations, and hundreds of thousands of deaths globally. Secondary infections further complicate influenza’s high morbidity and mortality, and significantly factored into the severity of the 1918, 1968, and 2009 pandemics. The most common coinfections are bacterial, leading to bacterial pneumonia, though viral secondary infections also occur. Previous studies have shown that influenza can target innate responses and damage affected tissues, allowing for secondary infections. In this study we show that influenza virus targets not only innate immune responses but also the adaptive responses - specifically activated B cells, T cells, and NKT cells. Importantly, we demonstrate that infection with influenza virus can attenuate the adaptive responses to prior influenza vaccination and to other respiratory pathogen vaccinations, in humans and in mouse models. This occurs through a viral hijacking of the normal immune responses by taking advantage of elevated expression of sialic acid receptors on activated lymphocytes to preferentially infect and kill immune responders. Our findings provide a novel potential mechanism for the high incidence of secondary respiratory infections due to bacteria and other viruses, as well as for vaccine failures against other infectious agents during influenza seasons.