骨髓移植受者巨细胞病毒感染的研究

目的　探讨巨细胞病毒在骨髓移植受者中的感染状况。方法　应用酶联免疫吸附反应方法、免疫组化方法及多聚酶链反应术后同步测定 3 0例骨髓移植受者的抗巨细胞病毒抗体、巨细胞病毒抗原和巨细胞病毒核酸 ,共 2 71例次。结果　骨髓移植受者的抗CMVIgG和抗CMVIgM阳性率分别为 10 0 %和 1 8% ;CMV Ag阳性细胞数平均为 5 1± 3 9/5× 10 4WBC ,阳性率为 3 6 2 % ;CMV DNA的阳性率为 42 4%。两者同时阳性共86份 ,占 3 1 7%。结论　骨髓移植受者术后存在不同程度的CMV感染。临床上同步开展CMV抗体、抗原及核酸的检测对早期诊断骨髓移植受者术后CMV感染具有重要意义     

肾移植受者巨细胞病毒感染及免疫抑制剂的影响

目的　探讨肾移植受者巨细胞病毒 (CMV)感染率及免疫抑制剂对其的影响。方法　 2 14例肾移植受者术后静滴甲泼尼龙 (Mp)、抗淋巴细胞球蛋白 (AL G)作为诱导期免疫抑制治疗 ;基础免疫抑制剂治疗为环孢素 A、泼尼松和硫唑嘌呤 ;急性排斥反应时静滴 Mp治疗 ,无效时给予 AL G或 OKT;采用免疫细胞化学法测定外周血白细胞 CMV- PP6 5抗原 ,术后头 3个月每周 1次。结果　 2 14例肾移植受者中 ,12 6例 (6 1.7%)术后发生 CMV感染 ;70例 (32 .7%)发生急性排斥反应 ,其中 5 2例 (74 .3%)发生 CMV感染 ,明显高于无急性排斥反应患者的5 1.4 %(P<0 .0 1) ;在 12 6例 CMV感染和 88例无 CMV感染的肾移植受者中 ,诱导期免疫抑制剂 AL G平均剂量分别为 (14 .1± 1.3)支和 (13.2± 0 .9)支 (P>0 .0 5 ) ,平均疗程分别为 (4.7± 1.3) d和 (4.4± 0 .9) d(P>0 .0 5 ) ,急性排斥反应发生率分别为 4 2 .3%和 2 0 .5 %(P<0 .0 1)。结论　肾移植受者术后 CMV感染率高 ;术后短期的AL G诱导治疗可能不增加 CMV感染发生率 ;急性排斥反应后免疫抑制剂尤其是 AL G或 OKT3的使用与 CMV感染密切相关。     

人巨细胞病毒被膜磷蛋白pp65的检测及其应用

目的:建立一种快速简便诊断肾移植受者人巨细胞病毒(HCMV)活动性感染的方法.方法:运用免疫组织化学的催化信号扩增法检测外周血白细胞中的人巨细胞病毒被膜磷蛋白pp65,巨细胞病毒信使核糖核酸(pp67-mRNA)检.测法作比较.结果:检测105例肾移植受者中,HCMVpp65抗原阳性45例,pp67-mRNA检测阳性40例,pp65抗原阳性细胞数为(70±43)个/2×105个WBC,而有症状的CMV病25例,抗原阳性细胞指数为(85±44)个/2×105个WBC.对照组100名健康人,pp65抗原检测全为阴性.pp65的敏感性、特异性分别是100%、88.9%.结论i该法敏感,简便,可作为肾移植术后HCMV病的早期诊断并可指导抗病毒治疗.     

HLA、PRA技术在肾移植中应用的临床研究

目的　研究人类白细胞抗原 (HLA)配型和群体反应性抗体 (PRA)在肾移植受者 ,尤其在致敏受者的临床意义。方法　对 70例肾移植受者采用微量序列特异引物聚合酶链反应法检测HLA -I类抗原和HLA -Ⅱ类抗原 ;莱姆德细胞板通过补体依赖微量细胞毒性试验检测受者的群体反应性抗体 (PRA)。结果　 (1)对 70例受者按交叉反应组配型原则 ,供、受者 0、1个位点错配分别为 10例 (14 .3% )和 2 4例 (34.3% ) ,明显高于传统HLA抗原配型结果(P <0 .0 5 ) ,术后急性排斥反应及移植肾功能延迟恢复率 ,两种配型方法间的差异无显著性。 (2 ) 70例受者中女 2 4例PRA阳性 9例 (37.5 % ) ,男 4 6例PRA阳性 5例 (10 .9% ) ,女性组明显高于男性组 (P <0 .0 5 )。 (3) 70例受者中 30例术前输血者PRA阳性 12例 (40 % ) ;4 0例无输血者PRA阳性 2例 (5 % ) ,术前输血组PRA阳性率明显高于无输血组 (P <0 .0 0 1)。 (4)PRA阳性组尤其是阳性率≥ 5 0 %的受者 ,其急性排斥发生率明显高于PRA阴性组 (P <0 .0 5 )。结论　反复输血、妊娠是PRA阳性的危险因素 ,采用交叉反应组配型和免疫吸附 ,对减少PRA阳性者肾移植排斥反应、提高移植成功率和移植物存活率具有重要意义。     

杭州地区育龄妇女TORCH感染调查分析

目的了解杭州地区育龄妇女TORCH感染情况及其流行特点。方法应用ELISA技术检测4798例育龄妇女血清中TORCH特异性抗体。结果 TOX-IgM、RV-IgM、CMV-IgM、HSV-Ⅰ-IgM及HSV-Ⅱ-IgM的阳性率分别为0.69%、1.06%、0.54%、0.6%及0.23%;TOX-IgG、RV-IgG、HSV-Ⅰ-IgG及HSV-Ⅱ-IgG的阳性率分别为2.38%、73.9%、10.3%及6.29%。TORCH感染者中,TOX冬季高发,阳性率为1.26%;CMV,HSV-Ⅰ,HSV-Ⅱ感染率没有明显季节差异。TORCH感染率没有年龄段差异。结论季节和年龄对TORCH感染影响不明显,但是冬季对于预防TOX感染有重要意义。育龄妇女应进行TORCH感染的检测和预防,以提高生育质量。     

肾移植术后巨细胞病毒性肺炎临床分析

目的探讨肾移植术后巨细胞病毒(CMV)性肺炎临床特点、治疗和转归.方法采用免疫细胞化学法检测外周血白细胞CMV抗原诊断活动性CMV感染,CMV肺炎患者给予静滴更昔洛韦和(或)膦甲酸钠治疗,严重者停用或减少免疫抑制剂.结果 56例(3.1%)肾移植受者术后发生CMV肺炎,均有发热、干咳、X线胸片示间质性肺炎,31例(55.3%)出现低氧血症,27例需呼吸机辅助呼吸;17例严重CMV肺炎患者需停用免疫抑制剂;56例患者存活率为69.6%.结论肾移植术后CMV肺炎以间质性肺炎、低氧血症为突出表现,病死率高,更昔洛韦和膦甲酸钠是治疗CMV肺炎的有效药物.     

两种方案预防肾移植术后巨细胞病毒感染的临床观察

目的探讨针对性预防方案和普遍性预防方案在防治肾移植术后巨细胞病毒(CMV)感染中的临床疗效。方法回顾性分析128例肾移植受者的临床资料。按术后预防CMV感染方案的不同分为针对性预防组(56例)和普遍性预防组(72例)。针对性预防组:针对高危病例术后应用更昔洛韦预防CMV感染。普遍性预防组:所有病例术后常规应用更昔洛韦预防CMV感染。对两组受者的CMV感染率、耐药发生率、病死率及预防和治疗CMV感染的费用进行统计分析。结果针对性预防组CMV感染率为7.14%(4例)、耐药发生率为1.79%(1例),改用膦甲酸钠治愈;普遍性预防组CMV感染率为9.72%(7例)、耐药发生率为4.17%(3例),改用膦甲酸钠3例治愈,病死率为1.39%(1例)。两组受者的CMV感染率、耐药发生率及病死率差异均无统计学意义(P>0.05),普遍性预防组用于预防和治疗CMV感染的人均费用明显高于针对性预防组(P<0.01)。结论肾移植术后针对性预防方案临床疗效优于普遍性预防方案,而且针对性预防方案更为经济,适合于我国的肾移植受者。     

永康市新生儿与婴幼儿TORCH感染情况结果分析

目的 了解永康市新生儿与婴幼儿TORCH的感染情况。方法 采用电化学发光（CLIA）法检测2 059例新生儿与婴幼儿血清中的TORCH特异性抗体,并进行分析。结果 2 059例TORCH检测结果中,TORCH-IgM总阳性率为3.45%,CMV-IgM、RV-IgM、TOX-IgM、HSV(I+Ⅱ)-IgM的阳性率分别为2.82%、0.49%、0.05%、0.15%,CMVIgM阳性率最高;TORCH-IgG总阳性率为99.76%,CMV-IgG、RV-IgG、TOX-IgG、HSV(I+Ⅱ)-IgG的阳性率分别为98.49%、85.33%、1.02%、80.57%。不同年龄组IgM与IgG抗体检测结果中CMV-IgM、TOX-IgM、HSV(I+Ⅱ)-IgM、CMV-IgG、RV-IgG、HSV(I+Ⅱ)-IgG比较,差异有统计学意义（P<0.05）。不同性别TORCH-IgM与TORCH-IgG抗体检测结果比较,差异无统计学意义（P>0.05）。结论 永康市的新生儿与婴幼儿的TORCH的感染以CMV和RV为主,既往感染较高,急性感染较低,临床上应该加强对新生儿及婴幼儿的...     

孕妇人巨细胞病毒-PP65及IgM的检测分析

目的 探讨妊娠妇女人巨细胞病毒的感染状况及监测效果.方法 分别采用酶联免疫吸附试验和间接荧光免疫染色法检测2004年1月～2007年6月在深圳市福田区第二人民医院行产前检查的760例孕妇外周血人巨细胞病毒-PP65抗原血症和人巨细胞病毒-IgM.结果 孕妇人巨细胞病毒感染阳性率为4.87%,其中人巨细胞病毒-IgM抗体阳性率为1.58%(6/380),外周血白细胞人巨细胞病毒-PP65抗原血症的检测结果阳性率为8.16%(31/380).两种检测方法比较x2=18.99,P＜0.001,有非常显著性差异.结论 同时应用人巨细胞病毒-IgM抗体和人巨细胞病毒-PP65抗原检测方法可对孕妇妊娠早期人巨细胞病毒活动性感染进行监测及治疗指导.     

肾移植前HLA配型对抗体阴性和阳性低致敏患者移植后10年生存率的影响

目的研究肾移植患者应用人类白细胞抗原(HLA)配型对群体反应性抗体(PRA)阳性低致敏患者和群体反应性抗体PRA阴性患者移植后10年生存率的差异。方珐通过对97例肾移植术前HLA配型结果的观察,将PRA阳性百分率在10.71%~32.14%的低致敏患者与PRA阴性患者分为致敏组和非致敏组,在肾移植10年后生存率是否有差异的随访比较。结果在97例尸体肾移植受者中,肾移植术前群体反应性抗体(PRA)阳性百分率在10.71%~32.14%之间的有23例,占23.71%;另外,有74例移植术前为群体反应性抗体(PRA)阴性,占76.28%;目前移植肾10年后,有47例肾功能在正常范围内,其中,有8例肾功能在正常范围内的患者术前检测PRA为10.71%~32.14%,占28.57%;计算肾移植患者术前群体反应性抗体(PRA)阳性和阴性所占百分率与肾移植术后10年肾功能正常的患者群体反应性抗体(PRA)阳性和阴性所占百分率,差异无统计学意义(P0.05)。在肾移植10年后,47例肾功能正常的患者,其中,有8例PRA阳性检测为10.71%~32.14%的肾移植患者HLA-A、B、DR、位点6个抗原错配l~2个抗原;有20例PRA检测为阴性的肾移植患者HLA—A、B、DR、位点6个抗原错配1~2个抗原;有19例PRA检测为阴性的肾移植患者HLA_A、B、DR、错配3个或以上抗原,差异有统计学意义(P0.05)。结论良好的HLA配型可提高移植肾的10年生存率,在良好的HLA配型的基础上PRA阳性百分率为10.71%~32.14%的低致敏受者与PRA阴性的受者10年生存率无差异。     

Prevalence of antibodies to hepatitis C virus in hemodialysis patients and renal transplant recipients

This work was carried out to study the prevalence of hepatitis C virus (HCV) infection, its associated risk factors and possible routes of transmission in hemodialysis patients and renal transplant recipients. Ninety five patients and 15 normal controls were included in this study. Patients were classified into 3 groups: Group I (64 hemodialysis patients), Group II (16 renal transplant recipients) and Group III (15 patients with chronic renal insufficiency on conservative treatments). Each individual was subjected to full clinical examination, estimation of serum alanine aminotransferase (ALT), testing for antibodies to hepatitis C virus (anti-HCV), screening for hepatitis B surface antigen (HBsAg), antibodies to hepatitis B surface antigen (anti-HBs) and core antigen (anti-HBc) by modified ELISA technique. Anti-HCV was found in 87.5% of hemodialysis patients, 81.25% of renal transplant patients, 53.3% of the conservative group and in 13.3% of the control group. There was a significant correlation between the presence of anti-HCV and the duration on dialysis in groups I and II (p < 0.05), while no significant correlation was detected between HCV positive cases and the number of units of transfused blood in groups I and II (p > 0.05). Serum ALT was elevated in patients with HCV infection, but there was no significant correlation between the presence of anti-HCV and elevated ALT level among the examined groups of patients (p > 0.05). The prevalence of HCV infection was not correlated with the duration of renal transplantation and the type of immunosuppressive therapy (p > 0.05). Coinfection with HBV and HCV could occur, as previous infection with HBV was demonstrated. Anti-HBc was found in 51.8%, 66.7%, 37.5% of anti-HCV positive patients in groups I, II, II respectively. Anti-HBs was detected in 24.1% and 15.4% of anti-HCV positive in groups I and II. HBsAg was found only in 4.7% of anti-HCV positive hemodialysis.     

Hospitalizations for cytomegalovirus disease after renal transplantation in the United States

PURPOSE: Risk factors, sites, and mortality of hospitalized cytomegalovirus (CMV) disease in renal transplant recipients have not been studied in a national population. METHODS: Therefore, 33,479 renal transplant recipients in the United States Renal Data System from 1 July 1, 1994 to June 30, 1997 were analyzed in an historical cohort study of patients with a primary discharge diagnosis of CMV disease (ICD9 Code 078.5x). RESULTS: Renal transplant recipients had an incidence density of hospitalized CMV disease of 1.26/100 person years, and 79% of hospitalizations for CMV disease occurred in the first six months post transplant. The leading manifestation of hospitalized infection was pneumonia (17%). In logistic regression analysis controlling for transplant era, pre-transplant dialysis > or = 6 months, maintenance mycophenolate mofetil (MMF) therapy, and allograft rejection, but not induction antibody therapy, were significantly associated with hospitalized CMV disease. Compared with recipients with negative CMV serology (R-) who had donor kidneys with negative CMV serology (D-), D+/R- had the highest risk of hospitalization for CMV disease [adjusted odds ratio (AOR) 5.19, 95% confidence interval (CI) 3.89-6.93] followed by D+/R+ recipients, whereas D-/R+ were not at significantly increased risk. In Cox Regression analysis the relative risk of death associated with hospitalized CMV disease was 1.32 (95% CI 1.02-1.71). CONCLUSIONS: Even in modern era, renal transplant recipients were at high risk for hospitalizations for CMV disease, which were associated with decreased patient survival. Current prophylactic measures have apparently not reduced the high risk of D+/R- recipients. Prolonged pre-transplant dialysis and maintenance MMF should also be considered risk factors for hospitalized CMV infection, and prospective trials of prophylactic antiviral therapy should be performed in these subgroups.     

pp67-mRNA在肾移植术后人巨细胞病毒感染中的诊断价值

目的探讨pp67对。肾移植术后人巨细胞病毒（HCMV）活动性感染及指导抗病毒治疗上的作用。方法采用NASBA测定32例肾移植术后患者外周血中的pp67,同时通过免疫荧光技术（IFA）对早期抗原pp65（CMV-Agpp6S）的检测来判断HCMV活动性,术后第3周,第7周分别用ED-TA管采血5-7rnl,每人每次两管做实验样本,立即送检并将二者结果相比较。其中检测结果有一项阳性的患者,选择更昔洛韦进行对症抗病毒治疗,对pp67-mRNA和pp65抗原检测双阳性患者,在选择更昔洛韦对症治疗时,并随访观察每周采血行pp67检测CMV活动情况,同时CMV抗原血症法检测,将二者结果比较,了解pp67与HCMV活动性感染及CMV病的关系。结果共采集样本128份,其中44份样本CMV-Agpp65阳性,19份样本pp67-mRNA阳性,8例CMV-Agpp65和pp67-mRNA均为阳性。临床诊断为HCMV病患者12例。CMV-Agpp65抗原检测灵敏度（91．7％）高于pp67-mRNA（66．7％）,pp67-mRNA特异性（95．O％）高于CMV．Agpp65（50．0％）抗原检测。而在HCM~临床症状出现感染并治疗后期,随访发现选择以pp67作为抗病毒治疗指标较CMV-Ag更早转阴,可以明显缩短用药时间（P〈0．05）。结论CMV-Agpp65、pp67-mRNA对器官移植术后HCMV感染均具有诊断意义,应用NASBA法能更加快捷准确检测巨细胞病毒,pp67较准确地反映了肾移植术后HCMV的活动性,能更好的指导临床抗病毒治疗并提供了较客观的依据。     

移植患者免疫抑制剂治疗后感染多瘤病毒及巨细胞病毒的现状

目的 探讨移植患者在接受免疫抑制剂他克莫司(FK506)治疗后感染多瘤病毒(BKV)与巨细胞病毒(CMV)情况,为器官移植研究提供流行病学依据.方法 采用FQ-PCR检测605例肝、肾、骨髓移植患者BKV和CMV的感染载量,ELISA检测患者FK506的血药浓度,并对结果进行统计分析.结果 605份标本中,共检测BKV感染者79例,感染率为13.06％,CMV感染148例,感染率为24.46％,双重病毒感染者为35例,感染率为5.79％;肝移植患者感染BKV和CMV阳性率为12.61％和15.97％,肾移植则分别为13.33％和27.08％,而6例骨髓移植标本则未发现病毒感染;CMV感染阳性率明显高于BKV,而病毒感染阳性者,则其FK506血药浓度较高(P＜0.05).结论 移植患者在使用免疫抑制剂FK506后易感染BKV和CMV,并且感染程度与FK506血药浓度相关.     

霉酚酸浓度监测对肾移植受者移植后感染的预测价值初探

目的研究霉酚酸(mycophenolic acid,MPA)浓度监测对肾移植受者移植后感染的预测价值。 方法纳入四川大学华西医院临床诊断为感染的住院肾移植受者48例(感染组)、一般情况稳定且排除感染的肾移植受者68例(对照组),收集所有受者入院前、入院时及出院时服药前、服药后0.5 h、2 h、4 h MPA药物浓度(MPA-C₀、MPA-C_0.5、MPA-C₂、MPA-C₄)和简化药时曲线下面积(MPA Area Under Curve_0-4,MPA-AUC_0-4)、他克莫司(Tacrolimus,TAC)谷浓度(TAC-C₀)、相关实验室检查、影像学等辅助检查等资料。 结果感染组肾移植受者TAC-C₀在入院前后基本稳定,均接近稳定组水平(P>0.05)。入院前,感染组肾移植受者MPA-AUC_0-4及MPA-C₄显著高于对照组(P<0.05),MPA-C₀和MPA-C₂稍高于与对照组(P>0.05);入院时,除MPA-C₀明显低于对照组(P<0.05),MPA-C₂、 MPA-C₄及MPA-AUC_0-4在感染组稍低于对照组(P>0.05);出院时,感染组MPA各时点浓度和MPA-AUC_0-4均与对照组无显著差异(P>0.05)。 结论MPA-AUC_0-4、MPA-C₄对肾移植受者感染发生有早期预示作用,霉酚酸治疗药物浓度监测有助于肾移植受者感染的预防控制。     

Effectiveness of preemptive therapy with ganciclovir in recipients of renal transplants at high risk (R-/D+) for the development of cytomegalovirus disease

Current management of renal transplant recipients who are CMV seronegative (R-) and receive an organ from a seropositive donor (D+) is controversial. These patients are at high risk for CMV disease and are usually treated with ganciclovir prophylaxis at variable dose and duration. An alternative to this approach is to administer ganciclovir only to those patients who are identified by virological markers to be at the highest risk to develop the disease (preemptive therapy). This prospective trial was conducted to asses the value of preemptive therapy to prevent CMV disease in R-/D+ kidney transplant recipients on triple drug immunosuppression without antilymphocyte induction. Sixteen adults receiving their first kidney transplant were enrolled and followed with pp65 antigenemia assay performed biweekly for the first 16 postransplant weeks, and then monthly to complete 12 months. Ganciclovir (5 mg/kg/day i.v., for 15 days) was administered as preemptive therapy upon detection of one or more antigen-positive cells per 150 x 10(3) peripheral blood leucocytes examined. For those receiving preemptive therapy, pp65 antigenemia was also repeated after completion of the regimen. CMV antigenemia was detected in 7/16 patients. At mean follow-up of 9 months (4-12 m) none of the 16 patients developed CMV disease. CMV serology (IgM) became positive in all patients after the first antigenemia result. The last follow-up mean serum creatinine (SCr) level was similar in both groups (1.35 mg/dL). In CMV R-/D+, the use of preemptive therapy guided by pp65 antigenemia is effective in preventing CMV disease. By using this strategy, 9 of 16 patients were spared ganciclovir prophylaxis with no effect on rejection or CMV disease. The clinical benefit and cost/effectiveness of this strategy should be evaluated against universal prophylaxis in these high-risk patients.     

心脏死亡器官捐献肾移植受者术后医院感染目标性监测

目的探讨心脏死亡器官捐献(DCD)肾移植受者术后医院感染发病率及病原体分布,为制定相应预防和控制措施提供理论依据。方法采用前瞻性研究方法对某三级医院2014年1月—2016年12月DCD肾移植受者进行医院感染目标性监测,分析DCD肾移植受者术后医院感染的发病率、医院感染病原学特点。结果 2014年1月—2016年12月共监测DCD肾移植患者313例,其中发生医院感染患者48例,共63例次,医院感染发病率为15.34%,例次发病率为20.13%。2016年DCD肾移植受者术后医院感染发病率为10.11%(19/188),2014年为28.57%(14/49),2015年为19.74%(15/76),各年份医院感染发病率比较,差异有统计学意义(P0.05)。居前三位的医院感染部位分别为下呼吸道(22/63,34.92%)、手术部位(16/63,25.39%)及血液系统(11/63,17.46%)。共检出病原体42株,主要为革兰阴性菌(27株,64.29%),其次是真菌(9株,21.43%)和革兰阳性菌(6株,14.28%);居前三位的病原体依次为肺炎克雷伯菌(9株,21.43%)、热带假丝酵母菌(7株,16.67%)、大肠埃希菌(5株,11.90%)。42株病原体中多重耐药菌(MDRO)15株(35.71%),其中革兰阴性菌10株(66.67%),以耐碳青霉烯类肠杆菌科(4株)及不动杆菌属(3株)为主;革兰阳性菌5株(33.33%),以耐甲氧西林金黄色葡萄球菌(3株)为主。结论 DCD肾移植受者术后医院感染发病率较高,应采取综合干预措施加强对下呼吸道感染、手术部位感染及血流感染的预防和控制,同时加强对MDRO感染的预防和控制,改善抗菌药物使用策略降低碳青霉烯类耐药菌株的产生。     

Relationship between cytomegalovirus and colonization of the oropharynx by gram-negative bacilli following renal transplantation.

Numerous investigators have reported an increased incidence of pneumonia caused by Gram-negative bacilli and other secondary pathogens in transplant recipients infected by cytomegalovirus (CMV). To determine if CMV infections are related to colonization of the upper respiratory tract by Gram-negative bacilli, we examined prospectively 22 renal transplant recipients with sequential bacteriological, virological and biochemical examinations performed just prior to and at various times after transplantation. Only 11% of subjects had Gram-negative bacilli isolated from gargle specimens prior to transplantation, as compared to 54% after transplantation. More importantly, after transplantation, subjects with active CMV infections were more likely to have prolonged oropharyngeal carriage of Gram-negative bacilli than subjects without CMV infections (36% v. 25%). During active CMV infections, the rate at which Gram-negative bacilli were isolated from gargle specimens rose from 28 to 47%. During culture-positive CMV infections, the isolation rate reached 57% and was significantly different from that of CMV-negative samples (P less than 0.01). The increased rate of Gram-negative bacillary isolation from gargle specimens during CMV infections was not a function of type of immunosuppressive agents used, rejection episodes, antibiotic administration, concomitant hepatitis B, Epstein-Barr (EBV) virus, or herpes simplex virus infections, or alterations in salivary fibronectin concentrations.     

Multi-antigenic human cytomegalovirus mRNA vaccines that elicit potent humoral and cell-mediated immunity

A cytomegalovirus (CMV) vaccine that is effective at preventing congenital infection and reducing CMV disease in transplant patients remains a high priority as no approved vaccines exist. While the precise correlates of protection are unknown, neutralizing antibodies and antigen-specific T cells have been implicated in controlling infection. We demonstrate that the immunization of mice and nonhuman primates (NHPs) with lipid nanoparticles (LNP) encapsulating modified mRNA encoding CMV glycoproteins gB and pentameric complex (PC) elicit potent and durable neutralizing antibody titers. Since the protective correlates in pregnant women and transplant recipients may differ, we developed an additional mRNA vaccine expressing the immunodominant CMV T cell antigen pp65. Administration of pp65 vaccine with PC and gB elicited robust multi-antigenic T cell responses in mice. Our data demonstrate that mRNA/LNP is a versatile platform that enables the development of vaccination strategies that could prevent CMV infection and consequent disease in different target populations.