细菌性痢疾简称菌痢,是一种常见的由志贺菌属引起的多发性消化道传染病.全球每年志贺菌导致的发病人数估计为1.65亿,约16万病例死亡[1].尽管近30年来细菌性痢疾病死率显著下降,但是发病率一直居高不下,在贫穷落后的国家和地区仍对儿童造成严重的疾病负担.儿童频繁发生感染性腹泻容易导致发育迟缓和营养不良,影响认知能力的发展,同时增加了肺炎和麻疹等其他传染病等感染死亡的可能性[2].抗生素的滥用以及人口国际流动使得耐药/多耐药菌群在全球传播,开发有效的痢疾疫苗成为公共卫生重点.痢疾疫苗的研究虽取得了不少进展,但至今仍未有大规模上市使用的痢疾疫苗.本文对痢疾的流行特征、疫苗研发和临床试验结果等研究进展作简要综述,为下一阶段痢疾疫苗的开发和临床试验设计提供参考.

BackgroundThis was a single-center, randomized, double-blind, parallel control study evaluating the immunogenicity and safety of a two-dose schedule of serogroups ACYW meningococcal polysaccharide conjugate vaccine with tetanus toxoid (TT) conjugate protein, in infants and toddlers of 3–35 months old.Method720 participants were stratified according to the age of 3–5 months old, 6–11 months old, and 12–35 months old and randomly assigned with an equal ratio to two different dose groups, i.e., 40- and 20-μg doses. Blood samples were taken from all participants before the first vaccination and 30 days after the full-course vaccination to detect the serogroups ACYW meningococcal antibodies. All adverse events occurred within 30 days after vaccination of each dose, and serious adverse events occurred within six months after full-course vaccination were collected for safety evaluation. This study was registered at the China drug trial registration with the identifier CTR 20182031.ResultsAfter 30 days of full-course vaccination, 92.78 % (95 % CI: 85.70 %-100.00 %) showed the immune response against all serogroups in both high-dose and low-dose groups by rabbit serum bactericidal antibody assay (rSBA) and the geometric mean titer (GMT) of all serogroups showed a high level (74.6–505.8, 95 % CI: 56.4–615.7). However, no significant difference between different dose groups was observed (P > 0.05). The common local and systemic adverse events in both groups were redness (3 %-7%), and fever (26 %-65 %), respectively. In addition, the grade 3 adverse event related to the vaccine was fever (1.67 %-12.50 %). No serious adverse event was reported to be associate with the vaccination.ConclusionThe serogroups ACYW meningococcal polysaccharide conjugate vaccine was safe and effective in the population aged 3–35 months. The vaccine efficacy and safety of the 20-μg dose group were not less than that of the 40-μg dose group.

No licensed Shigella vaccine is presently available globally. A double-blinded, randomized, placebo-controlled, age descending phase II clinical trial of a bivalent conjugate vaccine was studied in China. The vaccine ZF0901 consisted of O-specific polysaccharides purified and detoxified from lipopolysaccharide (LPS) of S. flexneri 2a and S. sonnei and covalently bonded to tetanus toxoid. A total of 224, 310, and 434 children, consented by parents or guardians, aged 3 to 6 and 6 to 12 months and 1 to 5 years old, respectively, were injected with half or full doses, with or without adjuvant or control Hib vaccine. There were no serious adverse reactions in all recipients of ZF0901 vaccine independent of age, dosage, number of injections, or the adjuvant status. Thirty days after the last injection, ZF0901 induced robust immune responses with significantly higher levels of type-specific serum antibodies (geometric mean concentrations (GMCs) of IgG anti-LPS) against both serotypes in all age groups compared with the pre-immune or the Hib control (p < 0.0001). Here, we demonstrated that ZF0901 bivalent Shigella conjugate vaccine is safe and immunogenic in infants and young children and is likely suitable for routine immunization.

目的 评价一种国产23价肺炎球菌多糖疫苗(PPV23)在≥2岁人群中的免疫原性和安全性.方法 采用随机、盲法、平行对照、非劣效Ⅲ期临床试验,在广西壮族自治区招募≥2岁健康受试者,按1:1比例随机接种1剂国产PPV23(试验组)或已上市的进口 PPV23(对照组);检测免疫前和免疫后30d血清中23种肺炎链球菌(Spn)血清型特异性IgG抗体,比较试验组和对照组免疫后抗体阳转率和几何平均浓度(GMC);收集免疫后30d内所有不良事件和6个月内严重不良事件,比较两组不良事件发生率.结果 938名试验组和936名对照组受试者接种PPV23后23种Spn血清型IgG抗体阳转率分别为61.19％-98.29％和59.51％-98.18％;两组各血清型抗体阳转率的率差为-6.26％-7.64％,95％CI下限均大于-10％.试验组和对照组免疫后各血清型抗体GMC增长倍数分别为2.81-11.19和2.78-13.16;两组GMC比值为0.82-1.36,95％CI下限均大于0.67.试验组和对照组总不良事件发生率分别为32.56％(309/949)和32.24％(306/949)(Fisher确切概率法,P = 0.922).结论 2岁健康人群接种国产PPV23的免疫原性和安全性良好,非劣于已上市的进口 PPV23.