An mRNA vaccine elicits STING-dependent antitumor immune responses

Lipid-formulated RNA vaccines have been widely used for disease prevention and treatment,yet their mechanism of action and individual components contributing to such actions remain to be delineated.Here,we show that a therapeutic cancer vaccine composed of a protamine/mRNA core and a lipid shell is highly potent in promoting cytotoxic CD8+T cell responses and mediating anti-tumor immunity.Mechanistically,both the mRNA core and lipid shell are needed to fully stimulate the expression of type I interferons and inflammatory cytokines in dendritic cells.Stimulation of interferon-βexpression is exclusively dependent on STING,and antitumor activity from the mRNA vaccine is significantly compromised in mice with a defective Sting gene.Thus,the mRNA vaccine elicits STING-dependent antitumor immunity.

A core-shell structured COYID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity

Although inoculation of COVID-19 vaccines has rolled out globally,there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all countries.Here,we report on the development of a highly efficacious mRNA vaccine,SW0123 that is composed of sequence-modified mRNA encoding the full-length SARS-CoV-2 Spike protein packaged in core-shell structured lipopolyplex(LPP)nanoparticles.SWOT 23 is easy to produce using a large-scale microfluidics-based apparatus.The unique core-shell structured nanoparticle facilitates vaccine uptake and demonstrates a high colloidal stability,and a desirable biodistribution pattern with low liver targeting effect upon intramuscular administration.Extensive evaluations in mice and nonhuman primates revealed strong immunogenicity of SW0123,represented by induction of Th1-polarized T cell responses and high levels of antibodies that were capable of neutralizing not only the wild-type SARS-CoV-2,but also a panel of variants including D614G and N501Y variants.In addition,SW0123 conferred effective protection in both mice and non-human primates upon SARS-CoV-2 challenge.Taken together,SW0123 is a promising vaccine candidate that holds prospects for further evaluation in humans.

Antibody-dependent cellular cytotoxicity response to SARS-CoV-2 in COVID-19 patients

Antibody-dependent cellular cytotoxicity(ADCC)responses to viral infection are a form of antibody regulated immune responses mediated through the Fc fragment.Whether severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)triggered ADCC responses contributes to COVID-19 disease development is currently not well understood.To understand the potential correlation between ADCC responses and COVID-19 disease development,we analyzed the ADCC activity and neutralizing antibody response in 255 individuals ranging from asymptomatic to fatal infections over 1 year post disease.ADCC was elicited by 10 days post-infection,peaked by 11-20 days,and remained detectable until 400 days post-infection.In general,patients with severe disease had higher ADCC activities.Notably,patients who had severe disease and recovered had higher ADCC activities than patients who had severe disease and deceased.Importantly,ADCC activities were mediated by a diversity of epitopes in SARS-COV-2-infected mice and induced to comparable levels against SARS-CoV-2 variants of concern(VOCs)(B.1.1.7,B.1.351,and P.1)as that against the D614G mutant in human patients and vaccinated mice.Our study indicates anti-SARS-CoV-2 ADCC as a major trait of COVID-19 patients with various conditions,which can be applied to estimate the extra-neutralization level against COVID-19,especially lethal COVID-19.