Journal
SCIENCE
Volume 367, Issue 6480, Pages 869-+Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aau0810
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Funding
- NIH [AI089779, AI070785, AI097696]
- China National Megaprojects for Major Infectious Diseases [2018ZX10301403]
- National Natural Science Foundation [81822045]
- Hundred-Talents program of Sun Yat-sen University
- MGH ECOR [230002]
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Current influenza vaccines only confer protection against homologous viruses. We synthesized pulmonary surfactant (PS)-biomimetic liposomes encapsulating 2',3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), an agonist of the interferon gene inducer STING (stimulator of interferon genes). The adjuvant (PS-GAMP) vigorously augmented influenza vaccine-induced humoral and CD8(+) T cell immune responses in mice by simulating the early phase of viral infection without concomitant excess inflammation. Two days after intranasal immunization with PS-GAMP-adjuvanted H1N1 vaccine, strong cross-protection was elicited against distant H1N1 and heterosubtypic H3N2, H5N1, and H7N9 viruses for at least 6 months while maintaining lung-resident memory CD8(+) T cells. Adjuvanticity was then validated in ferrets. When alveolar epithelial cells (AECs) lacked Sting or gap junctions were blocked, PS-GAMP-mediated adjuvanticity was substantially abrogated in vivo. Thus, AECs play a pivotal role in configuring heterosubtypic immunity.
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