Durable and enhanced immunity against SARS-CoV-2 elicited by manganese nanoadjuvant formulated subunit vaccine

Dear editor,Vaccines are the most efficient and effective means to prevent infectious diseases,but improving the long-term protective efficacy is still a major challenge in contemporary vaccine development.1 The waning immunity varies depending on the diversification of the pathogen and the number of booster doses.1 Strategies to overcome this warrant is using adjuvants that amplify the immune response,and drive the production of memory B and T cells or long-lived plasma cells that recognize the pathogen for durable protection.2–4 Although existing adjuvants have achieved promising results,research on generating durable protective immunity is lacking in promoting vaccine development and staying ahead of global pandemics such as coronavirus disease 2019(COVID-19).The precisely designed nanoadjuvants can enhance lymph node targeting and increase antigenpresenting cell(APCs)uptake,achieving the co-delivery of adjuvants and antigens and activating innate and adaptive immune responses.5 Previously,we reported a manganese nanoadjuvant(MnARK)and receptor-binding domain(RBD)monomer antigen formulated nanovaccine.6 MnARK transported antigens to lymph nodes,activated the STING pathway,elicited strong neutralizing abilities and increased immune memory T cell percentage against the infection of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).6 Regarding the long-term protection potential of MnARK for subunit vaccine development,we further explored the durable immune regulation abilities of MnARK to a SARS-CoV-2 RBD dimer antigen,which has been used in an approved COVID-19 subunit vaccine ZF2001 with aluminum adjuvant(alum).7,8 TEM result revealed that RBD dimer could interact with BSA on MnARK surface and epitope can be well preserved(Supplementary Fig.1a).The size and zeta potential of MnARK-RBD dimer nanovaccine was~58 nm and-14 mV,respectively(Supplementary Fig.1b,c).

STING and TLR9 agonists synergistically enhance the immunogenicity of SARS-CoV-2 subunit vaccine

Vaccines that are reliable and efficacious are essential in the fight against the COVID-19 pandemic.In this study,we designed a dual-adjuvant system with two pathogen-associated molecular patterns(PAMPs),MnOx and CpG.This system can improve the retention of antigens at the injection site,facilitate pro-inflammatory cytokines secretion,further recruit and activate dendritic cells(DCs).As a result,antigens can be delivered to lymph nodes specifically,and adaptive immunity was strengthened.The immunized group showed an enhanced and broadened humoral and cellular immune response in systemic immunity and lung protection when combined with a tandem repeat-linked dimeric antigen version of the SARS-CoV-2 receptor binding domain(RBDdimer).Remarkably,even with a significant reduction in antigen dosage(three times lower)and a decrease in injection frequencies,our nanovaccine was able to produce the highest neutralizing antibody titers against various mutants.These titers were four-fold higher for the wild-type strain and two-fold higher for both the Beta and Omicron variants in comparison with those elicited by the Alum adjuvant group.In conclusion,our dual-adjuvant formulation presents a promising protein subunit-based candidate vaccine against SARS-CoV-2.

卟啉–石墨炔衍生物的光热/光动力联合治疗

在本研究中,我们设计合成了两种卟啉修饰的新型石墨炔衍生物GDYO–TPP和GDY–TPP,它们在有机溶剂和水中具有良好的分散性及优异的生物相容性.研究发现GDYO–TPP和GDY–TPP不仅具有优异的光热转换性能,还具有优异的产生单线态氧能力,并可用于肿瘤的光热/光动力联合治疗,在动物体内表现出优异的肿瘤细胞生长抑制作用,且无毒副作用.进一步研究表明卟啉与石墨炔之间的高效电子转移使得共轭连接的GDY–TPP的光热/光动力联合治疗效果要优于非共轭连接的GDYO–TPP,实现了通过控制石墨炔中功能基团的键合方式对其光热/光动力联合治疗效果的调控,为设计新型功能石墨炔和光热/光动力联合治疗肿瘤提供了新思路.

Direct site-specific treatment of skin cancer using doxorubicin-loaded nanofibrous membranes

Doxorubicin(DOX) is widely used in cancer therapy. However, its application is sometimes limited by its adverse cardiotoxicity and delivery pathways. In our study, we prepared a topical implantable delivery device for controlled drug release and site-specific treatment. The core region consisted of poly(lactic co-glycolic acid) and poly-caprolactone, whereas the shell region was composed of cross-linked gelatin.DOX was enclosed in the core region of a core-shell nanofiber obtained by electrospinning. This implantable delivery device was implanted on the top of the melanoma in a mouse model, which had shown a DOX-controlled release profile with sustained and sufficient local concentration against melanoma growth in mice with negligible side effects. Compared with the traditional intravenous administration,the implantable device allows precisely localized treatment and therefore can reduce the dose, decrease the injection frequency, and ensure antitumor efficacy associated with lower side effects to normal tissues. Using a coaxial electrospinning process, it is promising to deliver different hydrophobic or hydrophilic drugs for direct tumor site-specific therapy without large systemic doses and minimized systemic toxicity.

New Insights from Chemical Biology:Molecular Basis of Transmission,Diagnosis,and Therapy of SARS-CoV-2

Coronavirus disease 2019(COVID-19)is caused by a novel strain of coronavirus,designated as severe acute respiratory syndrome coronavirus 2(SARSCoV-2).It has caused a global pandemic rapidly sweeping across all countries,bringing social and economic hardship to millions.Most countries have implemented early warning measures to detect,isolate,and treat patients infected with SARS-CoV-2.This minireview summarizes some of those steps,in particular,testing methods and drug development in the context of chemical biology,and discusses the molecular basis of COVID-19’s virulent transmissibility.

C60(OH)n-loaded nanofibrous membranes protect HaCaT cells from ROS-associated damage

Environmental stress factors could lead to the excess generation of reactive oxygen species（ROS） that induces various forms of skin damage related to oxidative stress. Polyhydroxylated fullerene derivative C（60）（OH）n, acting as an effective agent for prevention of skin aging, is widely used in the lotion and sunscreens in the field of cosmetics, but rarely used in the masks. In this study, we prepared C（60）（OH）n loaded nanofibrous membranes to protect human keratinocyte cells from ROS-associated damage and suppress the elevation of intracellular ROS and Ca（2＋） along with the apoptotic cell death. Two FDAapproved biodegradable polymers, PLGA and PCL, have been used for making the electrospun nanofibers,with C（60）（OH）n added to the polymers as an antioxidant. The nanofibrous membranes with good biocompatibility might be potentially applied in clinical practice to reduce skin aging.