Active Immunization with Extracellular Vesicles Derived from Staphylococcus aureus Effectively Protects against Staphylococcal Lung Infections, Mainly via Th1 Cell-Mediated Immunity.
Staphylococcus aureus is an important pathogenic bacterium that causes various infectious diseases. Extracellular vesicles (EVs) released from S. aureus contain bacterial proteins, nucleic acids, and lipids. These EVs can induce immune responses leading to similar symptoms as during staphylococcal infection condition and have the potential as vaccination agent. Here, we show that active immunization (vaccination) with S. aureus-derived EVs induce adaptive immunity of antibody and T cell responses. In addition, these EVs have the vaccine adjuvant ability to induce protective immunity such as the up-regulation of co-stimulatory molecules and the expression of T cell polarizing cytokines in antigen-presenting cells. Moreover, vaccination with S. aureus EVs conferred protection against lethality induced by airway challenge with lethal dose of S. aureus and also pneumonia induced by the administration of sub-lethal dose of S. aureus. These protective effects were also found in mice that were adoptively transferred with splenic T cells isolated from S. aureus EV-immunized mice, but not in serum transferred mice. Furthermore, this protective effect of S. aureus EVs was significantly reduced by the absence of interferon-gamma, but not by the absence of interleukin-17. Together, the study herein suggests that S. aureus EVs are a novel vaccine candidate against S. aureus infections, mainly via Th1 cellular response.
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Seng Jin
SJ
Choi
Department of Medicine, Ewha Womans University School of Medicine and Ewha Institute of Convergence Medicine, Ewha Womans Medical Center, Seoul, Republic of Korea.
Min-Hye
MH
Kim
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Jinseong
J
Jeon
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Oh Youn
OY
Kim
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Youngwoo
Y
Choi
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Jihye
J
Seo
Academy of Immunology and Microbiology (AIM), Institute for Basic Science (IBS), Pohang, Republic of Korea; Department of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Sung-Wook
SW
Hong
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Won-Hee
WH
Lee
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Seong Gyu
SG
Jeon
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea.
Yong Song
YS
Gho
Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Republic of Korea.
Young-Koo
YK
Jee
Department of Medicine, Ewha Womans University School of Medicine and Ewha Institute of Convergence Medicine, Ewha Womans Medical Center, Seoul, Republic of Korea.
Yoon-Keun
YK
Kim
D056704:Adaptive Immunity; D000818:Animals; D000917:Antibody Formation; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology*; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D013203:Staphylococcal Infections / Q000276:immunology / Q000517:prevention & control*; D013209:Staphylococcal Vaccines / Q000276:immunology / Q000627:therapeutic use*; D013211:Staphylococcus aureus / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology; D014611:Vaccination
D020381:Interleukin-17; D013209:Staphylococcal Vaccines; D051193:Toll-Like Receptors