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.

Environmental siblings of black agents of human chromoblastomycosis

Agents of human chromoblastomycosis,a skin disease almost exclusively caused by members of the order Chaetothyriales,are assumed to be traumatically inoculated into the skin with sharp environmental materials such as plant thorns or wooden splinters carrying the respective opportunist.In the supposition that such fungi should have their main habitat in the environment,we investigated the occurrence of black fungi in living areas of patients with chromoblastomycosis.In South America Fonsecaea agents are prevalent as agents of the disease,while also related Cladophialophora species,known from other types of skin infections,are known from the continent.Ninety environmental isolates were preliminarily selected as possible agents of chromoblastomycosis,based on morphology.Judging from ITS sequence data isolates were attributed to the genera Cladophialophora,Cyphellophora,Exophiala,Fonsecaea,Phialophora,and Veronaea.A total of 45 fungi morphologically identified as Fonsecaea or Cladophialophora isolated from debris and thorns of living prickly plants in Brazil were processed for taxonomic studies.Phylogenetic analysis revealed that the isolates indeed belonged to the Chaetothyriales,but only rarely an agent of chromoblastomycosis was concerned;only two strains of F.pedrosoi and one F.monophora were isolated from debris plants.The remaining isolates belonged to hitherto unknown molecular siblings of Fonsecaea.Two novel taxa are introduced.

Experiences and Lessons of Combating COVID-19 that Chinese Experts Shared with the World

At the end of 2019,a novel viral pneumonia was detected in Wuhan City(1)and has spread rapidly throughout 215 countries,areas,and territories with more than 3.8 million cases and over 260,000 deaths as of May 8,2020.This pneumonia,later named coronavirus disease 2019(COVID-19),has become a global public security challenge.

Cyphellophora and its relatives in Phialophora: biodiversity and possible role in human infection

Cyphellophora is a genus of black yeast-like fungi characterised by having simple phialides with multiseptate,curved conidia.Judging from SSU and LSU data,Cyphellophora was found to be located in a well-supported clade within the Chaetothyriales comprising a number of species occurring on human skin and nail.Cyphellophora is phylogenetically close to Phialophora europaea,P.reptans and P.oxyspora,though morphologically these species produce singlecelled phialoconidia rather than multiseptate ones.Pseudomicrodochium suttonii and P.fusarioides have dark colonies and phylogenetically fit in with Cyphellophora;the type species of Pseudomicrodochium,P.aciculare,has similar,septate conidia but has a hyaline thallus.In the present study,multilocus phylogenetic analyses were combined with morphology and physiology.Sequences of the internal transcribed spacer region,the DNA dependent RNA polymerase II largest subunit and the partial beta tubulin gene were analysed for a set of 30 strains.Two novel species,Cyphellophora pauciseptata and Phialophora ambigua were discovered.Cyphellophora eucalypti was reduced to synonymy of C.guyanensis.The role of the studied fungi between colonization and infection of human skin was discussed.Putative virulence factors for these black yeast-like fungi were hypothesized to be the ability to assimilate monoaromatic hydrocarbons,to produce melanin pigments,and to tolerate the temperature of epidermal human skin.