Influenza virus causes 3-5 million severe infections and 250,000-690,000 deaths worldwide each year, posing a tremendous threat to people’s lives and public health. Due to the constant mutations of the hemagglutinin (HA) and neuraminidase (NA) genes of the influenza virus, the mismatch between the predicted vaccine viral strains and strains in circulation annually has dramatically restricted the efficacy of the vaccine. Compared with replicating vaccines like natural viral infections and live attenuated influenza vaccines, non-replicating influenza vaccines induce poor T cell immunity in the respiratory tract and fail to induce strong protective immune responses. Therefore, safe and potent mucosal adjuvants are urgently needed to potentiate protective immunity against heterosubtypic viral infections.
On Feb. 21, the research article titled “Pulmonary surfactant–biomimetic nanoparticles potentiate heterosubtypic influenza immunity” by the research teams led by Lu Lu and Jiang Shibo from the School of Basic Medical Sciences, Fudan University and Mei X. Wu from Massachusetts General Hospital of Harvard Medical School, was published in Science. Their findings reveal the function and mechanism of biomimetic nanoparticles as a mucosal adjuvant for universal influenza vaccines.
The researchers synthesized pulmonary surfactant (PS) – biomimetic liposomes encapsulating 2′,3′-cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) to simulate influenza viral infection. They found PS-GAMP escaped immune surveillance after intranasal immunization, activating the STING pathway in both AMs and AECs without breaching PS and alveolar epithelial barriers. Through this mechanism, cGAMP promotes effective humoral and CD8+ T cell protective immune responses to resist the attack of heterogeneous influenza viruses. The study sheds light on the pivotal role AECs play in generating broad cross-protection against various influenza viruses. Thus, PS-GAMP is a promising mucosal adjuvant for “universal” influenza vaccines.
On the same day, a commentary article titled “Toward a universal flu vaccine” based on the research was published in the Perspective column of Science. The article evaluates the efficacy of cGAMP as an adjuvant for mucosal influenza vaccines and their crucial effects on cross-protective T cells in humans and other natural hosts for influenza viruses. It believes that effective adjuvants and targeted delivery systems combined with broadly protective vaccine antigens to elicit both cross-reactive CD8+ T cells and cross-protective antibodies may represent the most effective approach for urgently-needed universal influenza vaccines.
The teams led by research fellow Lu Lu and Prof. Jiang Shibo have been committed to the research of drugs and vaccines for emerging and re-emerging infectious diseases, while the laboratory of Dr. Mei X. Wu focuses on the research of adjuvants and biomimetic drug delivery systems.
The research was supported by Biosafety Level 3 Laboratory, Fudan University and Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University.
Pulmonary surfactant–biomimetic nanoparticles potentiate heterosubtypic influenza immunity:
https://dx.doi.org/10.1126/science.aau0810
Toward a universal flu vaccine:
https://science.sciencemag.org/content/367/6480/852
Editor: Lu Lu, Li Yijie
