简介：AbstractSevere fever with thrombocytopenia syndrome (SFTS), caused by a novel identified bunyavirus SFTS virus (SFTSV), was an emerging viral infectious disease that was firstly reported in China. There are no licensed vaccines and therapeutics against SFTSV currently. B-Propiolactone (BPL) inactivated whole virions of SFTSV strain AH12 were prepared as experimental vaccine in different antigen dose with or without Al(OH)3 adjuvant. The experimental SFTS vaccine was a satisfying immunogen, which could efficiently trigger the development of high levels of SFTSV NP-specific IgG antibodies and neutralizing antibodies against SFTSV Strain HB29 in BALB/c and C57/BL6 mice, and could induce SFTS virus-specific cellular immune responses to a certain extent. A single dose of vaccine was immunogenically insufficient in BALB/c mice; the second and third dose resulted in significant boost in antibody response. The use of Al(OH)3 adjuvant resulted in higher antibody titers. The mediate-dose of vaccine could induce as high and equivalent level of antibody titer as that of high-dose. The experimental SFTS vaccine in mediate-and high antigen dose with adjuvant resulted in solid protection of C57/BL6 mice against wild-type SFTSV challenge with markedly accelerated virus clearance from blood and spleen compared with controls. The experimental SFTS vaccine prepared in this study could efficiently elicit virus specific humoral and cellular immune responses in both BALB/c and C57/BL6 mice, and could protect C57/BL6 mice against SFTS virus challenge. These results supplied evidence that inactivated vaccine was a promising vaccine candidate for the prevention of SFTSV infection.

简介：与他们在文化经历无限的自强并且在身体区分进所有房间类型的能力，人的胚胎的干细胞(hESCs)为治疗保持大潜力当前不治之症。为针的绳索损害和有斑点的退化的二基于hESC的房间治疗被推进了进人的临床的试用。尽管有这快速的进步，基于hESC的房间治疗的一关键挑战是由接受者的导出hESC的房间的allogeneic免疫者拒绝。这个问题能被病人特定的体的房间的原子reprogramming被最近的突破与定义因素在导致的pluripotent干细胞(iPSCs)的技术减轻它能为房间治疗成为自体同源的房间的可更新的来源。然而，揭示反常epigenetics，genomic稳定性和iPSCs的immunogenicity的最近的研究在基于iPSC的治疗上提起了安全担心。与iPSC衍生物的immunogenicity有关的最近的调查结果将在这评论被总结。

简介：·AIM:Toinvestigatechangesinimmunogenicityofcryopreservedlimbalstemcells.·METHODS:Cryopreservedlimbalstemcells,freshprimarylimbalstemcellsandblankcontrolswereinoculatedsubcutaneouslyinC57BL-6miceandthepercentageofCD25cellsinlimbalexplantswasdeterminedbyflowcytometryatday21postinoculation.Morphologicalstudieswereperformedbylightandelectronmicroscopyoflimbalexplantsections.·RESULTS:Thenumberofregionalandsystemiclymphocytesderivedfromcryopreservedlimbalstemcellswaslowerthanthatfromfreshprimarylimbalstemcells.·CONCLUSION:Lymphocytesderivedfromcryopreservedlimbalstemcellsshowedchangesinimmunogenicity,butthesignificanceisunknown.Thecryopreservationandthawingmethodsawaitfurtherstudy.·

简介：HepatitisBvaccine,asthefirsthigh-effectiverecombinantcommercialvaccine,wassuccessfullydevelopedintheearly1980s.Sincethen,differentopinionshaveoccurredonthequalityofvaccineswithrapiddevelopmentoftargetgeneselecting,antigenexpressionsystem,andqualityevaluation.DifferentantigensofhepatitisBvaccinesarederivedfromdifferentexpressionsystem,andtherearealsosomedifferencesonmanufactureprocedureorglycosylateddegreeofantigen.

简介：CpGoligodeoxynucleotides(CpGODN)asadjuvanthavebeenextensivelystudiedinrecentyears.PhosphodiesterCpGODN(POCpGODN)canperfectlymimicbacterialDNAinenhancingimmuneresponsebutarevulnerabletonucleasesinvivo.ThisstudyaimedtoevaluatetheimmunostimulatorypotentialandsafetyofphosphodiesterCpGODNencapsulatedinnonphospholipidliposomes.BALB/cmicewereimmunizedintramuscularlywithdifferentformulationsofliposomes,CpGODNandhepatitisBsurfaceantigen(HBsAg).TheresultsdemonstratedthattheencapsulatedPOCpGODNwereprotectedagainstrapiddegradationinvivoandretainedtheiradjuvantactivity.POCpGODNencapsulatedwithHBsAginliposomesinducedstrongTh1-biasedorTh1/Th2mixedhumoralimmuneresponseinmicewiththemagnitudesimilartotheirphosphothioateequivalentinthesameformulation.HighIFN-gammaproductioninducedbythisformulationconfirmedthegenerationofstrongcellularimmuneresponse.Additionally,co-deliveryofHBsAgandPOCpGODNimprovedtheimmuneresponseoverthatobtainedwithseparatedelivery.Safetyexperimentshowedthatliposome-encapsulaedPOCpGODNandHBsAgcausedmildsystemicandmoderatelocaladversereaction.Inconclusion,ourdatashowsthatPOCpGODNencapsulatedinliposomesfullyexhibittheirTh1-typeadjuvantactivityandactasapotentialadjuvantforvaccines.

简介：AIM:Toconstructanon-resistantandattenuatedSalmonellatyphimurium(S.typhimurium)strainwhichexpressesconservativeregionofadhesionABofHelicobacterpylori(Hpylon)andevaluateitsimmunogenicity.METHODS:TheABgeneamplifiedbyPCRwasinsertedintotheexpressionvectorpYA248containingasdgeneandthroughtwotransformationsintroducedintothedeltaCya1deltaCrp1deltaAsdattenuatedSalmonellatyphimuriumstrain,constructingbalancedlethalattenuatedSalmonellatyphimuriumstrainsX4072(pYA248-AB).BridgedELISAmethodwasusedtomeasuretheexpressionofABantigeninsonicateandculturesupematant.AccordingtothemethoddescribedbyMeacock,stabilityoftherecombinantwasevaluated.Semi-lethalcapacitytestwasusedtoevaluatethesafetyofrecombinant.Theimmunogenicityofrecombinantwasevaluatedwithanimalexperiments.RESULTS:TheattenuatedS.typhimuriumX4072(pYA248-AB)whichexpressesABwassuccessfullyconstructed.Furthermore,bridgedELISAassayshowedthatthecontentofABinrecombinantX4072(pYA248-AB)culturesupematantwashigherthanthatwasinthalluslyticliquor.AndafterrecombinantX4072(pYA248-AB)wasculturedfor100generationswithoutselectionpressure,bheentirerecombinantbacteriaselectedrandomlycouldgrow,andtheABantigenwasdefectedpositivebyELISA.ThegrowthcurveoftherecombinantbacteriashowedthatthegrowthstatesofX4072(pYA248)andX4072(pYA248-AB)werebasicallyconsistent.ThesurvivalrateofC57BL/6wasstill100%,at30daftermicetakingX4072(pYA248-AB)1.0×l0^10cfuorally.OralimmunizationofmicewithX4072(pYA248-AB)inducedaspecificimmuneresponse.CONCLUSION:Invitrorecombinantplasmidappearstobestableandexperimentsonanimalsshowedthattherecombinantstrainsweresafeandimmunogenicinvitro,whichprovidinganewliveoralvaccinecandidateforprotectionandcareofHpyloriinfection.

简介：AbstractBackground:Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules.Methods:Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model.Results:In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53-24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06-1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16-2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25-2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36-14.71) or NVX-CoV2373 (GMR= 2.87; 95% CI: 1.08-3.91). No significant difference in the risk for SAEs was found in any comparisons.Conclusions:Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted.Registration:PROSPERO; https://www.crd.york.ac.uk/PROSPERO/; No. CRD42021278149.

简介：Theimmuneefficiencyofarecombinantadenovirustype5withtype35fibercontainingHIV-1gaggene(rAd5/F35-mod.gag)wasinvestigatedinBALB/cmice,inwhichtherAd5/F35-mod.gagwasfirstlyidentifiedwithPCR,thentransfectedto293cellsandtheinvitroexpressionlevelofGagproteinwasdeterminedbyWesternblottingandindirectimmuno-fluorescentassay.MicewereimmunizedwithintramuscularinjectionsofrAd5/F35-mod.gag,rAd5-mod.gagorDNAandwereboostedafter3weeks.Totesttheeffectofpre-existinganti-viralimmunityonimmunization,micewerealsoinjectedwithAd5-GFPvectorandthenimmunized4and7weekslaterwithAd5/F35-mod.gagvector.TheP24-specificIgGantibodyinseraofimmunizedmicewasdeterminedbyELISAandthespecificcytotoxicTlymphocyte(CTL)responsewasassayedbyintracellularcytokinestaining.ItwasdemonstratedthattherAd5/F35-mod.gagvectorcouldexpressefficientlytheHIVGagproteinin293cellsinvitroandinducestrongHIV-specificimmuneresponsesinvivo.ThestrongestCTLandserumIgGresponseoccurredwhenmicewereimmunizedtwicewithinjectionofrAd5/F35alone,buttheanti-Ad5antibodyafterprimaryinfectionwithadenoviruscouldinhibitthespecificimmuneresponsesinducedbyrAd5/F35vector.ItisconcludedthatsingleimmunizationwithrecombinantadenovirusrAd5/F35-mod.gagcaninducespecificCTLandserumIgGantibodyresponsesinmice,buttheimmunogenicityofrAd5/F35iscomparablyweakerthanthatofrAd5.

简介：瞄准：把在病人之间的标准肝炎B(HBV)种痘的反应与长期的丙肝作比较病毒(HCV)感染和健康个人。方法：这是未来的盒子控制研究。有长期的HCV感染和40健康控制的38个病人的一个总数被包括。种痘被20大杯recombinantHBsAg的注射在瞬间0，1和6点执行进三角肌肌肉。Anti-HBs集中是在最后剂量以后决定了3瞬间并且在二个组之间比较了。反应模式是被描绘(1)高反应当anti-HBs抗体效价是>时100IU/L，(2)低反应当效价是10-100IU/L时并且(3)没有反应当效价是<时10IU/L。结果：在耐心的组，有10/38(26.3%)非应答者，8/38(21.1%)低应答者并且20/38(52.6%)高应答者。在控制组的相应价值是2/40(5.0%)，7/40(17.5%)和31/40(77.5%)分别地。反应模式在二个组之间是统计上不同的。在里面多变量分析，吸烟是重要confounder，当HCV感染与更低的抗体反应失去了它的重要关联时。结论：有长期的HCV感染的病人趋于与健康个人相比对HBV种痘微弱地作出回应，尽管这关联不是独立的根据多变量分析。

简介：

简介：AbstractBackground:Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study.Methods:A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization.Results:V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95% CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively.Conclusions:The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy.Trial Registration:http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx? proj=124702).

简介：AbstractBackground:The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults.Methods:Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.Results:In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.Conclusions:Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.Trial Registration:http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx? proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).