Biosynthesis and Immunological Evaluation of a Dual-Antigen Nanoconjugate Vaccine Against Brucella melitensis

Brucellosis,caused by Brucella,is one of the most common zoonosis.However,there is still no vaccine for human use.Although some live attenuated vaccines have been approved for animals,the protection effect is not ideal.In this study,we developed a dual-antigen nanoconjugate vaccine containing both polysaccharide and protein antigens against Brucella.First,the antigenic polysaccharide was covalently coupled to the outer membrane protein Omp19 using protein glycan coupling technology,and then it was successfully loaded on a nano-carrier through the SpyTag/SpyCatcher system.After confirming the efficient immune activation and safety performance of the dual-antigen nanoconjugate vaccine,the potent serum antibody response against the two antigens and remarkable protective effect in non-lethal and lethal Brucella infection models were further demonstrated through different routes of administration.These results indicated that the dual-antigen nanoconjugate vaccine enhanced both T helper 1 cell(Th1)and Th2 immune responses and protected mice from Brucella infection.Furthermore,we found that this protective effect was maintained for at least 18 weeks.To our knowledge,this is the first Brucella vaccine bearing diverse antigens,including a protein and polysaccharide,on a single nanoparticle.Thus,we also present an attractive technology for co-delivery of different types of antigens using a strategy applicable to other vaccines against infectious diseases.

Simulations of standing wave effect,stop band effect,and skin effect in large-area very high frequency symmetric capacitive discharges

In this paper,Maxwell equations are coupled with a radially localized global model and an analytical sheath model to investigate the electromagnetic effects under various frequencies and electron powers in large-area very high frequency symmetric capacitive argon discharges.Simulation results indicate that both the vacuum wavelength and the sheath width decrease with frequency,leading to the reduced surface wavelength.As a result,the standing wave effect becomes pronounced,causing the fact that the radial profiles of the electron density,radio frequency voltage,and sheath width shift from uniform over center-high to multiple-node.When the frequency is close to or higher than the series resonance frequency,the surface waves cannot propagate to the radial center because of the significant radial damping.Due to the lack of power deposition near the radial center,the electron density is nearly zero there,i.e.the stop band effect.As power increases,the higher electron density leads to the decrease of the skin depth.Therefore,the importance of the skin effect gradually exceeds that of the standing wave effect,giving rise to the transition from the center-high to edge-high electron density profiles.The method proposed in this work could help to predict the plasma distribution under different discharge conditions in a few minutes,which is of significant importance in optimizing the plasma processing.

Enhanced protective immunity against SARS-CoV-2 elicited by a VSV vector expressing a chimeric spike protein

SARS-CoV-2 and SARS-CoV are genetically related coronavirus and share the same cellular receptor ACE2.By replacing the VSV glycoprotein with the spikes(S)of SARS-CoV-2 and SARS-CoV,we generated two replication-competent recombinant viruses,rVSVSARS-CoV-2 and rVSV-SARS-CoV.Using wild-type and human ACE2(hACE2)knock-in mouse models,we found a single dose of rVSV-SARS-CoV could elicit strong humoral immune response via both intranasal(i.n.)and intramuscular(i.m.)routes.Despite the high genetic similarity between SARS-CoV-2 and SARS-CoV,no obvious cross-neutralizing activity was observed in the immunized mice sera.In macaques,neutralizing antibody(NAb)titers induced by one i.n.dose of rVSV-SARS-CoV-2 were eight-fold higher than those by a single i.m.dose.Thus,our data indicates that rVSV-SARS-CoV-2 might be suitable for i.n.administration instead of the traditional i.m.immunization in human.Because rVSV-SARS-CoV elicited significantly stronger NAb responses than rVSV-SARS-CoV2 in a route-independent manner,we generated a chimeric antigen by replacing the receptor binding domain(RBD)of SARS-CoV S with that from the SARS-CoV-2.rVSV expressing the chimera(rVSV-SARS-CoV/2-RBD)induced significantly increased NAbs against SARS-CoV-2 in mice and macaques than rVSV-SARS-CoV-2,with a safe Th1-biased response.Serum immunized with rVSV-SARS-CoV/2-RBD showed no cross-reactivity with SARS-CoV.hACE2 mice receiving a single i.m.dose of either rVSV-SARS-CoV-2 or rVSV-SARSCoV/2-RBD were fully protected against SARS-CoV-2 challenge without obvious lesions in the lungs.Our results suggest that transplantation of SARS-CoV-2 RBD into the S protein of SARS-CoV might be a promising antigen design for COVID-19 vaccines.