全球视角:天花疫苗预防猴痘的感染的有效性、保护性、安全性分析

健康   2024-09-16 10:56   湖北  

猴痘病毒(MPXV)是一种DNA病毒,属于正痘病毒属 [1,2]。该属还包括天花病毒、疫苗病毒、牛痘病毒和骆驼痘病毒等[3]。MPXV可引起发热和皮损,与天花的症状较为相似,但区别在于猴痘病毒感染会引起淋巴结病变。MPXV起初主要在中非和西非流行,但现已成为一种全球性流行病[4,5]


2017~2018年间,尼日利亚爆发了大规模的猴痘疫情[6],英国、以色列和新加坡等国家也相继报告了猴痘病例[7]2022年1月至2024年4月期间,WHO共报告了全球117个国家的95226例猴痘病例[8],且发病率呈上升趋势,WHO宣布猴痘疫情为全球紧急卫生状况[9]。本次疫情中,18~44岁的男性病例数占总病例数的79.4%。男男性行为者(MSM)、双性恋者以及患有性传播疾病的人感染MPXV的风险很高[10],尤其是感染人类免疫缺陷病毒(HIV)的人死亡风险更高[11]。在2022年至2024年期间报告的猴痘病例中,MSM占比高达85.5%,合并HIV感染的病例数占51.9% [8],这意味着约有一半的猴痘患者可能会因HIV患上更严重的疾病[12]


由于猴痘疫情在全球爆发,并出现严重和致死病例,且尚无特效治疗药物和有效的临床治疗方法,急需安全有效的疫苗进行疫情防控。多篇研究已经发现天花疫苗能有效预防猴痘病毒的感染,且不良反应发生率低[13]。尽管前期研究对天花疫苗预防猴痘的有效性和安全性进行了评估,但将这些研究进行更为有效的总结,得出更全面、更可信的结论,对猴痘疫情的防控至关重要的。





2024年8月16日最新发表在Emerging Microbes & Infections期刊上的一项研究,总结了目前有关天花疫苗预防 MPXV 感染的研究;评估天花疫苗在现实世界中预防 MPXV 感染的有效性、保护性、安全性和交叉免疫原性,为广泛使用天花疫苗预防 MPXV 感染提供证据,并为疫苗接种方案提供指导。


doi: 10.1080/22221751.2024.2387442


材料与方法


研究人员从四个不同的数据库中总共检索了7,024项猴痘疫苗相关研究:其中2031项来自Embase,1143项来自PubMed,1862项来自Scopus,1988项来自Web of Science。去除其中的重复研究,剩下2799项研究。在对标题和摘要进行评估后,共选出80篇论文进行全文评审,最终选择了37项符合指定标准的研究进行数据分析和系统综述:11项疫苗有效性研究、7项疫苗保护研究、10项疫苗安全性研究。


图1. 文献检索过程


研究结果


1. 天花疫苗预防猴痘感染的有效性分析

研究人员对11项天花疫苗预防猴痘感染有效性方面的研究数据进行分析发现,与未接种天花疫苗相比,接种天花疫苗后猴痘感染风险降低了54%[14,15,16-24]


2. 天花疫苗对预防猴痘感染严重疾病的保护效果分析

研究人员对7项天花疫苗对猴痘病毒保护性方面的研究进行了评估,并根据猴痘的临床症状,并将其分为轻度或重度组。结果显示,天花疫苗使轻症病例的发病率增加了11%,但将猴痘严重疾病的风险降低了39%(图2)[21,25-30]


图2. 接种天花疫苗对猴痘轻度和重度疾病发病率的影响


研究人员还发现,接种一剂疫苗[21,25-27,29,30]可将严重疾病发病率降低29%,而接种两剂疫苗[28]使发病率降低了79%(图3A)。

  • 接种第一代天花疫苗[25,29]将严重疾病的发病率降低29%,而接种第三代天花疫苗[28,30]将发病率降低64%(图3B)。

  • 接种一剂疫苗的HIV阳性的猴痘受试者住院的可能性是未接种疫苗的HIV阳性猴痘受试者的0.28倍,但接种两剂疫苗的HIV阳性的猴痘受试者中,没有住院的报告[28]


图3. 天花疫苗降低猴痘重症疾病发病率情况

(A)接种一剂和两剂的天花疫苗降低重症发病率情况;(B)第一代和第三代天花疫苗降低猴痘重症疾病发病率情况


3. 天花疫苗接种后的安全性分析

研究人员在评估天花疫苗预防猴痘感染的安全性研究时发现,

  • 局部红斑[31-33,34-38]的发生率为56.3%,

  • 局部肿胀[31-37]的发生率为55.1%,

  • 局部硬结[31,32,38]的发生率为49.7%,

  • 局部瘙痒[32,34,35,36,37]的发生率为47.8%,

  • 局部疼痛[31-38]的发生率为47.2%(图4)。


图4. 天花疫苗接种的安全性分析

(A)接种后局部红斑;(B)接种后局部肿胀;(C)接种后局部硬结;(D)接种后局部瘙痒;(E)接种后局部疼痛。



讨论




















研究结果显示:


(1)天花疫苗接种可有效保护高危人群免受MPXV感染;


(2)接种天花疫苗显著降低了严重猴痘的发生率,且第三代天花疫苗保护效果优于第一代;


(3)HIV感染者应优先接种天花疫苗,以降低MPXV感染和重症风险;


(4)接种天花疫苗是安全的。接种天花疫苗后常见不良反应都很轻微,并在短时间内消失,没有对受试者的健康造成严重影响。



通过分析天花疫苗预防猴痘的研究数据发现,第三代天花疫苗显著降低了猴痘高风险人群的MSM和密切接触者中的患病率,以及猴痘严重疾病的发生率,保护效果优于以前的天花疫苗。同时,由于第三代天花疫苗是一种具有复制能力的高度减毒的疫苗,安全性更高[39,40],但免疫原性低于第一代疫苗[41]。因此,无论儿童是否接种过天花疫苗,都有必要补充接种第三代天花疫苗或猴痘疫苗,以应对猴痘疫情爆发。


通过对第三代天花疫苗接种针次数据进行了深入分析发现,接种一剂疫苗后MPXV感染的发生率降低了39%,接种两剂疫苗后降低了82%,但接种一剂或两剂疫苗的数据之间不存在显著差异。这可能有助于倡导在库存不足的情况下施用单剂量天花疫苗。


通过分析第三代天花疫苗引起的不良反应,研究人员发现第三代天花疫苗引起的不良反应大多为轻度局部症状,如局部红斑、肿胀、硬结、瘙痒、疼痛等。在不进行治疗的情况下,这些症状往往会在1~3天后消失[35],对患者的非危及生命的影响最小,该结果与先前报道天花疫苗安全性的研究结果一致。






















研究结果表明,在全球范围内,天花疫苗对猴痘都是安全有效的,而且第三代天花疫苗的保护效果可能不会受到接种剂量的影响。值得注意的是,天花疫苗的保护效果在MSM和HIV患者等高危人群中也显示出明显的优势,建议优先为高危人群,尤其是HIV感染者接种一剂第三代天花疫苗。然而,由于疫苗库存短缺,急需开展更多研究来比较不同剂量的疫苗的预防和治疗效果,以确保有限的疫苗能够得到更合理的分配。而考虑到以往接种天花疫苗后免疫反应降低、突破性感染的发生以及病毒的潜在变异,研究建议开发新一代更有效、更特异的天花疫苗来应对当前的天花疫情。


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