■用MVA-BN进行的暴露前疫苗接种已广泛用于预防水痘,以遏制2022年的爆发。许多国家已经确定了优先战略,给那些历史上接种天花疫苗的人服用单剂量,在供应不足的情况下迅速实现充足的覆盖。使用流行病学模型,实际有效性估计约为36%-86%,但未进行临床试验.关于MVA-BN免疫原性的数据目前很少,并且没有既定的保护关联。在2022年爆发的情况下,PLWH的免疫反应也没有得到很好的描述。
■在(T1)接受全疗程疫苗(对于有疫苗经验的或天花引发的单剂量和两个剂量)之前,以及最后一次剂量(分别为T2和T3)后一个月,从符合暴露前MVA-BN疫苗接种条件的参与者中收集血液样本。通过内部免疫荧光测定法测量MPXV特异性IgG,使用1:20作为筛选稀释,MPXV特异性nAbs通过50%斑块减少中和试验(PRNT50,起始稀释1:10),和产生IFN-γ的特异性T细胞对MVA-BN疫苗,通过ELISpot测定。配对或非配对t检验和Wilcoxon或Mann-Whitney检验用于分析IgG和nAbs。和T细胞反应,视情况而定。有疫苗经验的IgG和nAb应答的概率与在T1时无反应的参与者中估计未接种疫苗.McNemar试验用于评估总体和天花疫苗接种史疫苗接种对体液反应的影响。在T1时无反应的参与者中,通过逻辑回归比较了暴露组完成全周期后一个月成为应答者的比例,然后通过HIV状态分层进行了分析(相互作用测试)。还连续检查了反应,根据以前的天花疫苗接种,从基线到计划完成的差异的平均治疗效果(ATE)是在使用线性回归模型对HIV进行加权后估计的。在第一次MVA-BN剂量(T1)后,前瞻性收集了免疫后不良反应的自我报告(AEFI)。系统性(S-AEFI:疲劳,肌痛,头痛,GI效应,发冷)和局部(L-AEFI:发红,肿胀,疼痛)AEFI被分级为缺席(0级),轻度(1),中等(2),或严重(3)。使用单变量多项逻辑回归模型并在调整HIV状况后,分析了疫苗接种暴露组给药后30天内S-AEFIs和L-AEFIs的最大严重程度;对于每种症状,我们还使用非配对t检验比较了暴露组的平均持续时间.
■在包括的164名参与者中,90例(54.8%)是天花疫苗。中位年龄为49岁(IQR41-55)。在76名(46%)PLWH中,76%的CD4计数>500个细胞/μL。有证据表明,在施用MVA-BN疫苗后,IgG和nAbs滴度均增加。然而,没有证据表明从基线到完整周期完成的体液反应的潜在平均变化存在差异。非预科参与者。同样,在T1时对nAbs无反应的亚组中,没有证据表明全周期疫苗接种后血清转换率存在差异(Fisher精确检验p=1.00).在同样的分析中,对于nAbs的结果,有一些证据表明HIV(相互作用p值=0.17)会产生负面影响,因为HIV感染者(PLWH)的血清转化概率较低。非底漆,在PLWoH中看到了相反的情况。当连续评估反应时,我们观察到MVA-BN疫苗接种后,无论是引发的还是非引发的T细胞应答均增加.有证据表明,当使用2剂量与平均差异为-2.01log2(p≤0.0001)的单剂量策略,在控制艾滋病毒之后。暴露组没有观察到发展任何等级的AEFI的风险差异的证据,除了2级(中度)疲劳的风险较低,硬化和局部疼痛较低未灌注[OR0.26(0.08-0.92),p=0.037;或0.30(0.10-0.88),p=0.029和OR0.19(0.05-0.73),p=0.015,分别]。两组之间也没有发现症状持续时间差异的证据。
■疫苗接种周期结束后一个月对体液和细胞反应的评估表明,MVA-BN具有免疫原性,并且无论以前的天花疫苗接种史如何,最好采用两剂方案,尤其是在PLWH,最大化nabs响应。MVA-BN是安全的,耐受性好,首次接种疫苗后的2级反应原性高于有疫苗经验的个体,但没有证据表明这些不良反应的持续时间不同。需要进一步的研究来评估免疫的长期持续时间,并确定保护的具体相关性。
■该研究得到了国家传染病研究所LazzaroSpallanzaniIRCCS“2021年5×1000高级赠款”和意大利卫生部“RicercaCorrenteLinea2”的支持。
UNASSIGNED: Pre-exposure vaccination with MVA-BN has been widely used against mpox to contain the 2022 outbreak. Many countries have defined prioritized strategies, administering a single dose to those historically vaccinated for smallpox, to achieve quickly adequate coverage in front of low supplies. Using epidemiological models, real-life effectiveness was estimated at approximately 36%-86%, but no clinical trials were performed. Few data on MVA-BN immunogenicity are currently available, and there are no established correlates of protection. Immunological response in PLWH in the context of the 2022 outbreak was also poorly described.
UNASSIGNED: Blood samples were collected from participants eligible for pre-exposure MVA-BN vaccination before (T1) receiving a full course of vaccine (single-dose for vaccine-experienced or smallpox-primed and two-dose for smallpox vaccine-naïve or smallpox non-primed) and one month after the last dose (T2 and T3, respectively). MPXV-specific IgGs were measured by in-house immunofluorescence assay, using 1:20 as screening dilution, MPXV-specific nAbs by 50% plaque reduction neutralization test (PRNT50, starting dilution 1:10), and IFN-γ-producing specific T cells to MVA-BN vaccine, by ELISpot assay. Paired or unpaired t-test and Wilcoxon or Mann-Whitney test were used to analyse IgG and nAbs, and T-cell response, as appropriate. The probability of IgG and nAb response in vaccine-experienced vs. vaccine-naïve was estimated in participants not reactive at T1. The McNemar test was used to evaluate vaccination\'s effect on humoral response both overall and by smallpox vaccination history. In participants who were not reactive at T1, the proportion of becoming responders one month after full-cycle completion by exposure groups was compared by logistic regression and then analysed by HIV status strata (interaction test). The response was also examined in continuous, and the Average Treatment Effect (ATE) of the difference from baseline to schedule completion according to previous smallpox vaccination was estimated after weighting for HIV using a linear regression model. Self-reports of adverse effects following immunization (AEFIs) were prospectively collected after the first MVA-BN dose (T1). Systemic (S-AEFIs: fatigue, myalgia, headache, GI effects, chills) and local (L-AEFIs: redness, swelling, pain) AEFIs were graded as absent (grade 0), mild (1), moderate (2), or severe (3). The maximum level of severity for S-AEFIs and L-AEFIs ever experienced over the 30 days post-dose by vaccination exposure groups were analysed using a univariable multinomial logistic regression model and after adjusting for HIV status; for each of the symptoms, we also compared the mean duration by exposure group using an unpaired t-test.
UNASSIGNED: Among the 164 participants included, 90 (54.8%) were smallpox vaccine-experienced. Median age was 49 years (IQR 41-55). Among the 76 (46%) PLWH, 76% had a CD4 count >500 cells/μL. There was evidence that both the IgG and nAbs titers increased after administration of the MVA-BN vaccine. However, there was no evidence for a difference in the potential mean change in humoral response from baseline to the completion of a full cycle when comparing primed vs. non-primed participants. Similarly, there was no evidence for a difference in the seroconversion rate after full cycle vaccination in the subset of participants not reactive for nAbs at T1 (p = 1.00 by Fisher\'s exact test). In this same analysis and for the nAbs outcome, there was some evidence of negative effect modification by HIV (interaction p-value = 0.17) as primed people living with HIV (PLWH) showed a lower probability of seroconversion vs. non-primed, and the opposite was seen in PLWoH. When evaluating the response in continuous, we observed an increase in T-cell response after MVA-BN vaccination in both primed and non-primed. There was evidence for a larger increase when using the 2-dose vs. one-dose strategy with a mean difference of -2.01 log2 (p ≤ 0.0001), after controlling for HIV. No evidence for a difference in the risk of developing any AEFIs of any grade were observed by exposure group, except for the lower risk of grade 2 (moderate) fatigue, induration and local pain which was lower in primed vs. non-primed [OR 0.26 (0.08-0.92), p = 0.037; OR 0.30 (0.10-0.88), p = 0.029 and OR 0.19 (0.05-0.73), p = 0.015, respectively]. No evidence for a difference in symptom duration was also detected between the groups.
UNASSIGNED: The evaluation of the humoral and cellular response one month after the completion of the vaccination cycle suggested that MVA-BN is immunogenic and that the administration of a two-dose schedule is preferable regardless of the previous smallpox vaccination history, especially in PLWH, to maximize nAbs response. MVA-BN was safe as well tolerated, with grade 2 reactogenicity higher after the first administration in vaccine-naïve than in vaccine-experienced individuals, but with no evidence for a difference in the duration of these adverse effects. Further studies are needed to evaluate the long-term duration of immunity and to establish specific correlates of protection.
UNASSIGNED: The
study was supported by the National Institute for Infectious Disease Lazzaro Spallanzani IRCCS \"Advanced grant 5 × 1000, 2021\" and by the Italian Ministry of Health \"Ricerca Corrente Linea 2\".