Kunasekaran Mohana Priya, Chen Xin, Costantino Valentina, Chughtai Abrar Ahmad, MacIntyre Chandini Raina
Kirby Institute, Faculty of Medicine, University of New South Wales, Australia.
School of Public Health and Community Medicine, Faculty of Medicine, University of New South Wales, Australia.
Mil Med. 2019 Dec 1;184(11-12):e668-e679. doi: 10.1093/milmed/usz181.
Smallpox has been eradicated but advances in synthetic biology have increased the risk of its re-emergence. Residual immunity in individuals who were previously vaccinated may mitigate the impact of an outbreak, but there is a high degree of uncertainty about the duration and degree of residual immunity. Both cell-mediated and humoral immunity are thought to be important but the exact mechanisms of protection are unclear. Guidelines usually suggest vaccine-induced immunity wanes to zero after 3-10 years post vaccination, whereas other estimates show long term immunity over decades.
A systematic review of the literature was conducted to quantify the duration and extent of residual immunity to smallpox after vaccination.
Twenty-nine papers related to quantifying residual immunity to smallpox after vaccination were identified: neutralizing antibody levels were used as immune correlates of protection in 11/16 retrospective cross-sectional studies, 2/3 epidemiological studies, 6/7 prospective vaccine trials and 0/3 modeling studies. Duration of protection of >20 years was consistently shown in the 16 retrospective cross-sectional studies, while the lowest estimated duration of protection was 11.7 years among the modeling studies. Childhood vaccination conferred longer duration of protection than vaccination in adulthood, and multiple vaccinations did not appear to improve immunity.
Most studies suggest a longer duration of residual immunity (at least 20 years) than assumed in smallpox guidelines. Estimates from modeling studies were less but still greater than the 3-10 years suggested by the WHO Committee on International Quarantine or US CDC guidelines. These recommendations were probably based on observations and studies conducted while smallpox was endemic. The cut-off values for pre-existing antibody levels of >1:20 and >1:32 reported during the period of endemic smallpox circulation may not be relevant to the contemporary population, but have been used as a threshold for identifying people with residual immunity in post-eradication era studies. Of the total antibodies produced in response to smallpox vaccination, neutralizing antibodies have shown to contribute significantly to immunological memory. Although the mechanism of immunological memory and boosting is unclear, revaccination is likely to result in a more robust response. There is a need to improve the evidence base for estimates on residual immunity to better inform planning and preparedness for re-emergent smallpox.
天花已被根除，但合成生物学的进展增加了其重新出现的风险。以前接种过疫苗的个体中的残余免疫力可能会减轻疫情的影响，但残余免疫力的持续时间和程度存在高度不确定性。细胞介导免疫和体液免疫都被认为很重要，但确切的保护机制尚不清楚。指南通常表明疫苗诱导的免疫力在接种后3至10年降至零，而其他估计显示数十年的长期免疫力。
对文献进行系统综述，以量化接种天花疫苗后残余免疫力的持续时间和程度。
确定了29篇与量化接种天花疫苗后残余免疫力相关的论文：在16项回顾性横断面研究中的11项、3项流行病学研究中的2项、7项前瞻性疫苗试验中的6项以及3项建模研究中的0项中，中和抗体水平被用作保护的免疫相关指标。16项回顾性横断面研究一致显示保护持续时间超过20年，而建模研究中估计的最低保护持续时间为11.7年。儿童期接种疫苗比成年期接种疫苗提供更长的保护持续时间，多次接种似乎并未提高免疫力。
大多数研究表明残余免疫力的持续时间（至少20年）比天花指南中假设的更长。建模研究的估计值较低，但仍大于世界卫生组织国际检疫委员会或美国疾病控制与预防中心指南建议的3至10年。这些建议可能基于天花流行期间进行的观察和研究。天花流行期间报告的预先存在抗体水平>1:20和>1:32的临界值可能与当代人群无关，但已被用作根除后时代研究中识别具有残余免疫力人群的阈值。在针对天花疫苗接种产生的总抗体中，中和抗体已显示对免疫记忆有显著贡献。尽管免疫记忆和增强的机制尚不清楚，但再次接种可能会导致更强烈的反应。有必要改进关于残余免疫力估计的证据基础，以便更好地为天花重新出现的规划和准备提供信息。
