Troy Jesse D, Hill Heather R, Ewell Marian G, Frey Sharon E
The EMMES Corporation, 401 North Washington Street, Suite 700, Rockville, MD 20850, United States.
Saint Louis University School of Medicine, Department of Internal Medicine, Edward A. Doisy Research Center, 1100 S. Grand Bld., Saint Louis, MO 63104, United States.
Vaccine. 2015 Oct 5;33(41):5425-5431. doi: 10.1016/j.vaccine.2015.08.032. Epub 2015 Aug 28.
Previous research shows immune response to vaccination differs by sex but this has not been explored for IMVAMUNE, a replication-deficient smallpox vaccine developed in response to the potential for bioterrorism using smallpox.
We conducted a participant-level meta-analysis (N=275, 136 men, 139 women) of 3 randomized trials of IMVAMUNE conducted at 13 centers in the US through a federally-funded extramural research program. Studies were eligible for inclusion if they tested the standard dose (1×10(8)TCID₅₀/mL on Days 0 and 28) of liquid formulation IMVAMUNE, were completed at the time of our search, and enrolled healthy vaccinia-naïve participants. Models of the peak log₂ ELISA and PRNT titers post-second vaccination were constructed for each study with sex as a covariate. Results from these models were combined into random effects meta-analyses of the sex difference in response to IMVAMUNE. We then compared this approach with fixed effects models using the combined participant level data.
In each study the mean peak log₂ ELISA titer was higher in men than women but no single study demonstrated a statistically significant difference. Combination of the adjusted study-specific estimates into the random effects model showed a higher mean peak log₂-titer in men compared with women (absolute difference [men-women]: 0.32, 95% CI: 0.02-0.60). Fixed effects models controlling for study showed a similar result (log₂ ELISA titer, men-women: 0.34, 95% CI: 0.04-0.63). This equates to a geometric mean peak titer that is approximately 27% higher in men than women (95% CI: 3-55%). Peak log₂ PRNT titers were also higher (although not significantly) in men (men-women: 0.14, 95% CI: -0.30 to 0.58).
Our results show statistically significant differences in response to IMVAMUNE comparing healthy, vaccinia-naïve men with women and suggest that sex should be considered in further development and deployment of IMVAMUNE and other MVA-based vaccines.
先前的研究表明，疫苗接种的免疫反应存在性别差异，但针对因应对天花生物恐怖主义威胁而研发的复制缺陷型天花疫苗IMVAMUNE，尚未对此进行探讨。
我们通过一项由联邦政府资助的校外研究项目，对在美国13个中心开展的3项IMVAMUNE随机试验进行了受试者水平的荟萃分析（N = 275，男性136名，女性139名）。若研究测试了液体剂型IMVAMUNE的标准剂量（第0天和第28天为1×10⁸ TCID₅₀/mL），在我们检索时已完成，且纳入了未接种过痘苗的健康受试者，则该研究符合纳入标准。以性别作为协变量，为每项研究构建第二次接种后峰值log₂ ELISA和PRNT滴度的模型。将这些模型的结果合并为关于IMVAMUNE反应性别差异的随机效应荟萃分析。然后，我们使用合并的受试者水平数据，将这种方法与固定效应模型进行比较。
在每项研究中，男性的平均峰值log₂ ELISA滴度均高于女性，但没有一项研究显示出统计学上的显著差异。将调整后的各研究特异性估计值合并到随机效应模型中，结果显示男性的平均峰值log₂滴度高于女性（绝对差异[男性 - 女性]：0.32，95% CI：0.02 - 0.60）。控制研究因素的固定效应模型显示了类似的结果（log₂ ELISA滴度，男性 - 女性：0.34，95% CI：0.04 - 0.63）。这相当于男性的几何平均峰值滴度比女性高约27%（95% CI：3 - 55%）。男性的峰值log₂ PRNT滴度也更高（尽管不显著）（男性 - 女性：0.14，95% CI： - 0.30至0.58）。
我们的结果显示，在比较未接种过痘苗的健康男性和女性对IMVAMUNE的反应时，存在统计学上的显著差异，这表明在IMVAMUNE和其他基于MVA的疫苗的进一步研发和应用中应考虑性别因素。
