一氧化碳吸入对脂多糖诱导大鼠肺炎症细胞因子表达及损伤的影响

目的观察低浓度一氧化碳（CO）吸入对脂多糖（LPS）诱导大鼠肺促炎、抗炎细胞因子表达及损伤的影响。方法72只雄性sD大鼠随机均分为对照组（吸入空气）、单纯吸入CO组、LPS（5mg／kg）注入组及LPS注入＋CO吸入4组。酶联免疫吸附法测定吸入气体1、3、6h后肺肿瘤坏死因子α（TNF—α）、白细胞介素6及10（IL-6、IL-10）含量，光镜下评分比较损伤变化。结果LPS注入组TNF—α、IL-6及损伤评分高于，IL—10低于相应时间点的对照组及单纯CO吸入组（P均〈0．05），组内各时间点比较，只有损伤评分随观察时程延长而增加（P均〈0．05）；LPS注入＋CO吸入组TNF—α、IL-6及损伤评分低于，IL—10高于相应时间点的LPS注入组（P均〈0.05），组内各时间点比较，差异无统计学意义（P〉0．05）；对照组与单纯CO吸入组间及组内各时间点比较，差异均无统计学意义（P〉0.05）。结论低浓度CO吸入以非时间依赖方式抑制LPS诱导大鼠肺促炎介质产生、增强抗炎因子表达而减轻损伤。     

感染性休克患者血清细胞因子表达及其意义

目的　探讨感染性休克患者血清肿瘤坏死因子 (INF) α ,白细胞介素 (IL) 6 ,IL 8的表达及意义。方法选择 5 6例感染性休克患者 ,将其分为感染性休克组与多器官功能障碍综合征 (MODS)组 ,另设 5 0例健康者为对照组。用酶联免疫吸附 (ELISA)法动态检测上述研究对象的血清INF α ,IL 6 ,IL 8含量 ,比较各组间的差异。结果感染性休克组及MODS组的血清细胞因子INF α ,IL 6 ,IL 8的表达均显著高于对照组 (均 P <0 .0 1) ,MODS组高于感染性休克组 (P <0 .0 1) ,且病死病例明显高于存活病例 (P <0 .0 5 )。IL 6与IL 8呈明显正相关。结论　血清细胞因子INF α ,IL 6 ,IL 8参与了感染性休克的发生、发展过程。动态监测血清细胞因子对于判断感染性休克患者病情的轻重 ,估计预后有一定价值。     

胃癌组织中CD4+、CD25+调节性T淋巴细胞的表达及意义

目的 探讨CD4+、CD25+调节性T淋巴细胞在胃癌患者胃组织中的表达及意义.方法 利用流式细胞仪对76例胃癌及癌旁组织中的CD4+、CD25+调节性T淋巴细胞与CD8+T淋巴细胞进行定量及量化关系分析.结果 CD4+、CD25+调节性T淋巴细胞的阳性率在胃癌、癌旁组织、正常时照组分别为(11.2±0.9)%、(6.4±1.1)%、(4.1±0.8)%.癌组织与癌旁组织和对照组比较,差异有统计学意义(t=2.03、2.05,P<0.05).在肿瘤组织,随着CD4+、CD25+调节性T淋巴细胞的增加,CD8+T淋巴细胞出现了快速减少趋势.而在癌旁组织中却没有此现象出现.结论 CD4+、CD25+调节性T淋巴细胞通过对CD8+T淋巴细胞的抑制参与胃癌细胞抗肿瘤免疫的作用.     

肝硬化患者外周血及腹水TNF-α、IL-6、IL-8与自发性细菌性腹膜炎关系的探讨

腹水是肝硬化患者的常见并发症之一 ,部分患者可进一步发展为自发性细菌性腹膜炎 (SBP) ,SBP起病凶险、发展快、死亡率高。我们通过对肝硬化腹水患者的外周血及腹水肿瘤坏死因子 -α(TNF -α)、白细胞介素 -6(IL -6)及白细胞介素 -8(IL-8)的测定来了解其与SBP的关系 ,为本病的临床诊断、治疗及使用拮抗剂来减轻肝脏损害及降低SBP的死亡率提供帮助。1　资料与方法1·1　一般资料　全部病例为 1997年 7月～ 2 0 0 2年 6月住院治疗的肝硬化病人 (均经B超及CT证实 ) 46例 ,其中乙肝后肝硬化 3 1例 ,血吸虫性肝硬化 12例 ,酒精性肝硬化 …     

恶性肿瘤的肺转移

肺是各种组织类型肿瘤发生转移的第二位易发器官 ,尸检中有 2 9%的病人死于肺转移性恶性肿瘤 ,肺是惟一转移部位的占 2 0 %。肿瘤的转移实际上是一个多步骤、多因素参与的复杂过程 ,与原发肿瘤组织学类型和解剖位置有关 ,四肢软组织肉瘤的早期转移 ,肺为惟一转移部位的占 60 %以上 ;与器官特异性有关 ,取决于自分泌因子 (ＡＭＦ)、表皮生长因子 (ＥＧＦ)、ＩＬ - 1、ＩＬ - 3、ＩＬ - 6、转移生长因子等 ,尤其是血管内皮生长因子 (ＶＥＧＦ)有极强的促分裂作用 ,目前研究的焦点之一 ,通过阻止肿瘤分泌ＶＥＧＦ而达到抑制肿瘤转移。1　肺转移…     

乙型肝炎后肝硬化T细胞亚群、肿瘤坏死因子-α、白细胞介素-6、白细胞介素-8的临床研究

目的 探讨乙型肝炎病毒(HBV)携带者及乙型肝炎后肝硬化患者T细胞亚群、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、IL-8的变化及意义.方法 利用流式细胞仪方法和酶联免疫吸附试验法分别检测30例HBV携带者(HBV携带者组)及27例乙型肝炎后肝硬化患者(乙型肝炎后肝硬化组)的T细胞亚群、TNF-α、IL-6、IL-8含量,并与20例正常对照者(正常对照组)进行比较.结果 乙型肝炎后肝硬化组及HBV携带者组与正常对照组比较,CD3+显著下降(0.5900±0.0305、0.6500±0.0502比0.7000±0.0554,P＜ 0.01);CD4+显著下降(0.2900±0.0283、0.3800±0.0306比0.4400±0.0411,P＜ 0.01);CD8+显著升高(0.2900±0.0152、0.2700±0.0238比0.2500±0.0459,P＜ 0.01或＜0.05);CD4+/CD8+乙型肝炎后肝硬化组显著低于正常对照组(1.03±0.10比1.73±0.16,P＜ 0.01),但HBV携带者组与正常对照组比较差异无统计学意义(1.71±0.18比1.73±0.16,P＞0.05);乙型肝炎后肝硬化组与正常对照组相比NK(CD16+ CD56)显著下降(0.1300±0.0541比0.1900±0.0742,P＜0.01),但HBV携带者组与正常对照组比较差异无统计学意义(0.1600±0.0539比0.1900±0.0742,P＞ 0.05),乙型肝炎后肝硬化组与HBV携带者组比较差异有统计学意义(P＜0.05);乙型肝炎后肝硬化组和HBV携带者组TNF-α显著升高[(307.00±38.28)、(113.00±18.61)μg/L比(101.00±13.90) μg/L,P＜ 0.01];IL-6显著升高[(184.60±18.86)、(68.10±7.58) μg/L比(63.40±7.04)μg/L,P＜0.01或＜0.05];IL-8显著升高[(1710.00±158.05)、(926.00±61.82) μg/L比(814.00±45.91)μg/L,P＜0.01].结论 T细胞亚群、TNF-α、IL-6和IL-8水平的高低,能够反映肝细胞损害的程度,可以作为临床上判断乙型肝炎严重程度和预后的重要指标.     

氟对人体血清免疫功能的影响

本文用酶联免疫吸附试验，单向免疫扩散等方法检测检测了氟暴露工人血清可溶性白细胞介素２受体α肿瘤坏死因子和免疫球蛋白ＩａＧ，ＩｇＭ，ＩｇＧ。结果显示工人血清ＴＮＦα含量与氟暴露工龈 关，表现为短期氟暴露人工ＴＮＦα增加，而长期氟暴露工人ＴＮＦα降低。     

CD4^＋CD25^＋调节性T细胞对哮喘大鼠气道炎症的影响

目的观察CD4^＋CD25^＋调节性T细胞（CD4^＋CD25^＋Treg）对哮喘大鼠气道炎症的影响。方法将卵白蛋白（OVA）免疫耐受大鼠CD4^＋CD25^＋Treg细胞过继转移给哮喘大鼠,然后观察支气管肺泡灌洗液（BALF）中细胞计数及分类,ELISA检测BALF中IL-4、IL-5和IFN-1及血清OVA特异性IgE含量,HE染色观察肺组织的病理改变。结果与哮喘组比较,过继转移CD4^＋CD25^＋Treg细胞后哮喘大鼠BALF中细胞总数、中性粒细胞和淋巴细胞百分率降低（P〈0．05）,嗜酸性粒细胞（Eos）百分率明显降低（P〈0．01）;BALF中IL4和IL-5含量明显降低,IFN-1含量明显升高,血清OVA特异性IgE含量明显降低（P〈0．05）;气道炎症明显减轻。结论过继转移OVA免疫耐受大鼠CD4^＋CD25^＋Treg细胞可以明显抑制哮喘的慢性气道炎症。     

支气管哮喘患者急性发作期痰和血浆IL-4和IFN-γ水平与肺通气功能的相关性研究

目的：研究支气管哮喘患者急性发作期痰和血浆IL-4和IFN-γ水平与肺通气功能的相关性关系。方法：急性发作期患者41例为实验组；缓解期患者34例为对照组；37例健康者为健康组。测定所有患者的通气功能及痰和血浆中IL-4和IFN-γ水平。分析IL-4和IFN-γ水平与肺通气功能之间的相关性。结果：（1）实验组通气功能、IFN-γ水平均显著低于对照组和健康组（P〈0．01）。（2）实验组痰液和血浆中IL-4的水平均显著高于对照组和健康组（P〈0．01）。（3）实验组痰和血浆中IL-4平均浓度与其相应肺通气功能指标均呈负相关；IFN-γ平均浓度与其相应肺通气功能指标均呈正相关。结论：支气管哮喘患者急性发作期痰和血液中IL-4水平与肺通气功能呈负相关；IFN-γ水平与肺通气功能呈正相关。     

妇科肿瘤患者血清中细胞因子的表达及意义

目的：研究妇科肿瘤患者血清中细胞因子的变化，探索与发病机理的相关性。方法：以双抗体夹心ＥＬＩＳＡ法对７９例妇科肿瘤患者血清中肿瘤坏死因子（ＴＮＦ－α）、白细胞介素－６（ＩＬ－６）、白细胞介素－８（ＩＬ－８）和白细胞介素－１０（ＩＬ－１０）水平进行了监测。结果：妇科恶性肿瘤组ＴＮＦ－α、ＩＬ－６、ＩＬ－８和ＩＬ－１０水平均明显高于正常对照组和妇科良性肿瘤组（Ｐ＜０．０１），其中尤以卵巢癌增高最为明显，其次为子宫内膜癌和滋养细胞肿瘤。结论：说明ＴＮＦ－α、ＩＬ－６、ＩＬ－８和ＩＬ－１０细胞因子可能参与肿瘤的形成和发展过程，并对妇科良、恶性肿瘤的鉴别诊断有一定意义。     

急性失血患者血浆白细胞介素-6、白细胞介素-8、肿瘤坏死因子-α和一氧化氮合酶的变化探讨

目的 探讨急性失血患者血浆白细胞介素(IL)-6、IL-8、肿瘤坏死因子(TNF)-α和一氧化氮合酶(NOS)变化及其意义.方法 入选25例急性失血患者(失血组)和25例健康体检者(对照组),采用酶联免疫吸附法检测两组血浆IL-6、IL-8、TNF-α和NOS水平.结果 失血组血浆IL-6、IL-8、TNF-α和NOS水平明显高于对照组(0.284±0.027比0.204±0.016、0.059±0.079比0.037±0.039、0.460±0.024比0.372±0.018、0.637±0.054比0.443±0.040,P＜ 0.05或＜0.01).结论 急性锐器刺割伤致失血易引起血浆IL-6、IL-8、TNF-α和NOS水平升高,IL-6、IL-8、TNF-α释放加重组织器官损伤及失血性休克发展.NOS水平升高促进一氧化氮的合成增加,在急性失血血容量不足时促进微循环灌注,缓解组织灌注不足,可能对机体起保护作用.     

高氧暴露对新生SD大鼠肺泡内白细胞介素-8及肿瘤坏死因子-α含量的影响

目的探讨新生SD大鼠高氧暴露后肺泡内白细胞介素(IL)-8及肿瘤坏死因子(TNF)-α的含量变化。 方法选择100只生后24 h的足月、健康SD大鼠为研究对象,按照随机数字表法,将其分为高氧组(n＝50)及空气组(n＝50)。高氧组大鼠持续吸入浓度≥95%的氧气,空气组大鼠置于空气中,并于给氧后第1、3、6、10、14天,每组每次各取10只大鼠进行肺泡灌洗,应用双抗体夹心酶联免疫吸附测定(ELISA)法检测肺泡灌洗液中IL-8及TNF-α含量。统计学比较两组新生SD大鼠肺泡灌洗液中IL-8及TNF-α含量差异,以及高氧组大鼠上述不同时间点IL-8及TNF-α含量差异。两组大鼠性别构成比及出生体重比较,差异无统计学意义(P>0.05)。实验过程中对动物的处置符合动物伦理学标准。 结果①高氧组大鼠在高氧暴露第14天出现生长迟缓,呆滞,体重不增,呼吸浅快,口唇发绀等不良表现。②高氧组新生SD大鼠第3、6、10、14天肺泡灌洗液中IL-8含量较空气组高[(262.4±12.5)×10^－15 g/L vs (94.0±12.5)×10^－15 g/L,(374.1±14.8)×10^－15 g/L vs (94.8±7.2)×10^－15 g/L,(345.7±17.5)×10^－15 g/L vs (94.5±4.3)×10^－15 g/L,(295.5±26.6)×10^－15 g/L vs (95.6±7.5)×10^－15 g/L],且差异有统计学意义(t＝36.909、58.033、43.981、22.878,P<0.05);高氧组新生SD大鼠第1、3、6、10、14天肺泡灌洗液中TNF-α含量较空气组高[(43.0±4.5)×10^－15 g/L vs (29.9±1.7)×10^－15 g/L,(59.3±7.0)×10^－15 g/L vs (33.3±4.1)×10^－15 g/L,(55.1±7.7)×10^－15 g/L vs (31.1±2.5)×10^－15 g/L,(43.2±5.1)×10^－15 g/L vs (31.2±3.4)×10^－15 g/L,(34.4±3.8)×10^－15 g/L vs (30.7±2.8)×10^－15 g/L],且差异有统计学意义(t＝－6.287、－10.190、－7.358、－2.508、－4.516,P<0.05)。③高氧组新生SD大鼠肺泡灌洗液中IL-8含量于第6天均分别较第1、3、10、14天高(t＝－50.812、－18.265、－3.910、－8.170,P<0.05),第10天较第14天高(t＝－4.987,P<0.05),且差异均有统计学意义;高氧组新生SD大鼠肺泡灌洗液中TNF-α含量于第3天均分别较第1、6、10、14天高(t＝－6.209、－3.719、－5.900、－9.974,P<0.05),第6天及第10天分别较第14天高(t＝－4.416、4.732,P<0.05),且差异均有统计学意义。 结论IL-8和TNF-α可能参与新生SD大鼠高氧肺损伤的早期炎症反应。     

2型糖尿病合并高血压患者大血管病变的炎性机制

目的探讨2型糖尿病合并高血压时慢性炎性因子与大血管病变的关系。方法131例2型糖尿病患者分为4组,比较各组糖尿病并发高血压和大血管病变时的细胞因子水平。结果正常对照与4组糖尿病亚组相比,CRP、IL-2、IL-6、IL-8、TNF-α、PAI-1水平差异均有统计学意义。糖尿病并大血管病组的CRP、IL-6、TNF-α、PAI-1水平显著高于糖尿病无大血管病变组(P<0.05);糖尿病高血压合并大血管病变组IL-6、TNF-α水平显著高于糖尿病合并大血管病变组(P<0.05)。IL-6、TNF-α与BM I、WHR、FFA、TC、FINS、UA均呈正相关,BM I、FINS作为独立因素影响IL-6、TNF-α的水平。结论IL-6、TNF-α可能在2型糖尿病大血管病变尤其同时合并高血压时发挥了一定的炎性作用。     

生脉散对大肠杆菌脂多糖诱导慢性肝衰竭大鼠细胞因子水平的影响

目的探讨生脉散对慢性肝衰竭大鼠大肠杆菌脂多糖（LPS）诱导细胞因子水平的影响。方法采用CCl。混合液腹腔注射复制慢性肝衰竭大鼠模型,观察LPS诱导2h后生脉散后对血清内毒素、细胞因子水平的影响。结果CCl。混合液能明显增加大鼠血清IL-6[（64．50±18．79）pg／mlVS（4．79±0．57）pg／m1]、ICAM-1[（25100．00±5258．85）pg／mlVS（4215．50±942．79）pg／m1]和TNF-α[（17．55±2．39）pg／mlVS（10．92±5．02）pg／m1]水平（P〈0．05）,但对血清LPS水平无明显影响[（0．058±0．007）EU／mlVS（0．040±0．002）EU／ml,P〉0．05];中药生脉散能显著降低CCl。慢性肝衰竭大鼠血清IL-6、ICAM-1和TNF-α水平[分别为（17．20±3．12）pg／ml、（9490．00±2725．78）pg／ml、（3．00±1．00）pg／ml,P〈0．05]。LPS攻击2h后能明显升高CCI。混合液大鼠血清LPS、TNF-α、IL-6、ICAM-1水平[分别为（0．501±0．019）EU／ml、（19750．00±9655．17）pg／ml、（5615．00±490．50）pg／ml、（41000．00±589．88）pg／ml,P〈0．01]。结论在慢性肝衰竭模型中,LPS能增加TNF-α,IL-6和ICAM-1等炎症因子水平,中药生脉散可降低LPS水平,并抑制LPS诱导的炎症因子水平,阻断了炎性介质及LPS本身对机体的损伤。     

Glutamine reduces the expression of leukocyte integrins leukocyte function–associated antigen-1 and macrophage antigen-1 in mice exposed to arsenic

Chronic arsenic exposure results in an increased oxidative stress and inflammation in the body. Glutamine (GLN) is an amino acid considered to have immunomodulatory effects and attenuate the inflammatory reaction. This study was designed to examine the effect of GLN supplementation on inflammatory-related leukocyte integrin expression and in vitro splenocyte cytokine production in mice exposed to arsenic. Mice were assigned to the control and experimental groups. The control group drank deionized water, whereas the experimental group drank deionized water containing 50 ppm of sodium arsenite. Each control and experimental group was further divided into 2 subgroups and fed diets for 5 weeks. One subgroup was fed a semipurified diet, whereas the other subgroup was fed a diet where part of the casein was replaced with GLN, which provided 25% of the total amino acid nitrogen. The results showed that plasma GLN levels of mice in the arsenic group were significantly lower than those in the control groups. Glutamine supplementation reversed the depletion of plasma GLN in the arsenic group. β₂ intergins, including leukocyte function–associated antigen-1 and macrophage antigen-1 expressed by leukocytes, were significantly higher in the arsenic group than the control groups. Glutamine supplementation reduced leukocyte integrin expression in mice exposed to arsenic. There were no differences in interleukin 4, interleukin 6, interferon γ, and tumor necrosis factor α production between the 2 arsenic groups when splenocytes were stimulated with mitogen. These results suggest that arsenic exposure results in depletion of plasma GLN and higher leukocyte integrin expression. Glutamine supplementation normalized the plasma GLN levels and reduced leukocyte leukocyte function–associated antigen-1 and macrophage antigen-1 expression. However, cytokine modulation may not be responsible for reducing leukocyte integrin expression in mice exposed to arsenic.     

Capsaicin attenuates palmitate-induced expression of macrophage inflammatory protein 1 and interleukin 8 by increasing palmitate oxidation and reducing c-Jun activation in THP-1 (human acute monocytic leukemia cell) cells

Capsaicin, a spicy component of hot peppers, has been shown to improve inflammatory disease and obesity. In this study, we tested the hypothesis that the anti-inflammatory activity of capsaicin can be used to improve free fatty acid (FFA)-induced inflammation by reducing gene expression of macrophage inflammatory protein 1 (MIP-1) and interleukin 8 (IL-8) in THP-1 (human acute monocytic leukemia cell) macrophages. To investigate whether capsaicin ameliorates palmitate-induced MIP-1 and IL-8 gene expressions, we treated THP-1 cells with palmitate in the presence or absence of capsaicin and measured MIP-1 and IL-8 by real-time polymerase chain reaction. To elucidate the mechanism by which capsaicin effects on palmitate-induced MIP-1 and IL-8 gene expressions, we performed immunoblotting with stress kinase-related antibodies and measured palmitate oxidation and palmitate oxidation-related gene expression. Palmitate and stearate but not the unsaturated FFA oleate significantly increased MIP-1 and IL-8 expressions in THP-1 macrophages. Treatment with capsaicin or FFA oxidation stimulators inhibited palmitate-induced MIP-1 and IL-8 expressions in THP-1 macrophages. Capsaicin increased the gene expression of carnitine palmitoyltransferase 1 and the β-oxidation of palmitate. Furthermore, capsaicin significantly reduced palmitate-stimulated activation of c-Jun N-terminal kinase, c-Jun, and p38. Our data suggest that the attenuation of palmitate-induced MIP-1 and IL-8 gene expressions by capsaicin is associated with reduced activation of c-Jun N-terminal kinase, c-Jun, and p38 and preserved β-oxidation activity.     

Immune responses elicited by a fourth dose of the HPV-16/18 AS04-adjuvanted vaccine in previously vaccinated adult women

Background

Vaccines are now available for the prevention of HPV-16/18-related cervical infections and pre-cancers, primarily targeting adolescent girls. Since the risk of HPV exposure potentially persists throughout a woman's sexual life, vaccine-derived immunity should be long-term. The current study, HPV-024 (NCT00546078, http://clinicaltrials.gov), assessed the immune memory in North American women who received three doses of HPV-16/18 AS04-adjuvanted vaccine 7 years earlier in HPV-001 (NCT00689741).

Methods

Women vaccinated in HPV-001 received a 4th-dose of the HPV-16/18 vaccine (024-4DV group, N = 65). Post 4th-dose immune responses were compared with post 1st-dose immune responses in cross-vaccination controls (024-3DV group, N = 50). Reactogenicity was compared between the 4th-dose and the 1st-dose administration.

Results

Pre 4th-dose, 100% of subjects in the 024-4DV group remained seropositive for anti-HPV-16/18 antibodies (ELISA). Compared to pre 4th-dose, GMTs for anti-HPV-16 and anti-HPV-18 antibodies were respectively 9.3-fold and 8.7-fold higher at day 7, and 22.7-fold and 17.2-fold higher at month 1. Compared to post 1st-dose, GMTs for anti-HPV-16 and anti-HPV-18 were respectively 80.5-fold and 205.4-fold higher at day 7, and 11.8-fold and 20.5-fold higher at month 1. Furthermore, 68.2% and 77.3% of women had HPV-16/18 specific memory B-cells, respectively, pre 4th-dose, rising to 100% one month post 4th-dose vaccination. The 4th-dose was generally well tolerated.

Conclusion

A 4th-dose of HPV-16/18 AS04-adjuvanted vaccine triggered a rapid and strong anamnestic response in previously vaccinated women, demonstrating vaccine-induced immune memory.     

Burden of pneumococcal disease due to serotypes covered by the 13-valent and new higher-valent pneumococcal conjugate vaccines in the United States

The addition of pneumococcal conjugate vaccines (PCVs) to the United States (US) national immunization program led to significant reductions in incidence, mortality, and associated sequelae caused by pneumococcal disease (PD) in children and adults through direct and indirect protection. However, there remains clinical and economic burden due to PD caused by serotypes not included in the current 13-valent PCV (PCV13) formulation. To address this unmet need, 15-valent PCV (PCV15) and 20-valent PCV (PCV20), containing additional serotypes to PCV13, were recently approved in the US for adults and are anticipated for pediatrics in the near future. The study objective was to estimate the annual number of cases, deaths, and economic burden of PD due to serotypes included in PCV13, PCV15, and PCV20 for both US pediatric and adult populations. An Excel-based model was developed to calculate clinical and economic outcomes using published age-group specific serotype coverage; incidence of invasive PD, community-acquired pneumonia, and acute otitis media; case fatality rates; and disease-related costs. The results showed that across all age groups, the estimated annual PD cases and associated deaths covered by PCV13 serotypes were 914,199 and 4320, respectively. Compared with PCV13 serotypes, the additional 2 and 7 serotypes covered by PCV15 and PCV20 were attributed with 550,475 and 991,220 annual PD cases, as well as 1425 and 3226 annual deaths, respectively. This clinical burden translates into considerable economic costs ranging from $903 to $1,928 million USD that could be potentially addressed by PCV15 and PCV20. The additional serotypes included in PCV20 contribute substantially to the clinical and economic PD burden in the US pediatric and adult populations. Despite the success of the PCV13 pediatric national immunization program and increased adult uptake of PCV13 and 23-valent polysaccharide vaccine, broader PCV serotype coverage is needed across all ages to further reduce pneumococcal disease burden.