Noverr Mairi C, Yano Junko, Hagensee Michael E, Lin Hui-Yi, Meyaski Mary C, Meyaski Erin, Cameron Jennifer, Shellito Judd, Trauth Amber, Fidel Paul L
Department of Microbiology and Immunology, Tulane University School of Medicine.
Center of Excellence in Oral and Craniofacial Biology, LSU Health School of Dentistry.
Med Res Arch. 2023 Feb;11(2). doi: 10.18103/mra.v11i2.3598.
Mortality in COVID-19 cases was strongly associated with progressive lung inflammation and eventual sepsis. There is mounting evidence that live attenuated vaccines commonly administered during childhood, also provide beneficial non-specific immune effects, including reduced mortality and hospitalization due to unrelated infections. It has been proposed that live attenuated vaccine-associated non-specific effects are a result of inducing trained innate immunity to function more effectively against broader infections. In support of this, our laboratory has reported that immunization with a live attenuated fungal strain induces a novel form of trained innate immunity which provides protection against various inducers of sepsis in mice via myeloid-derived suppressor cells. Accordingly, we initiated a randomized control clinical trial with the live attenuated Measles, Mumps, Rubella (MMR) vaccine in healthcare workers in the greater New Orleans area aimed at preventing/reducing severe lung inflammation/sepsis associated with COVID-19 (ClinicalTrials.gov Identifier: NCT04475081). Included was an outcome to evaluate the myeloid-derived suppressor cell populations in blood between those administered the MMR vaccine vs placebo. The unanticipated emergency approval of several COVID-19 vaccines in the midst of the MMR clinical trials eliminated the ability to examine effects of the MMR vaccine on COVID-19-related health status. Unfortunately, we were also unable to show any impact of the MMR vaccine on peripheral blood myeloid-derived suppressor cells due to several inherent limitations (low percentages of blood leukocytes, small sample size), that also included a collaboration with a similar trial (CROWN CORONATION; ClinicalTrials.gov Identifier: NCT04333732) in St. Louis, MO. In contrast, monitoring the COVID-19 vaccine response in trial participants revealed that high COVID-19 antibody titers occurred more often in those who received the MMR vaccine vs placebo. While the trial was largely inconclusive, lessons learned from addressing several trial-associated challenges may aid future studies that test the non-specific beneficial immune effects of live attenuated vaccines.
新冠病毒感染病例的死亡率与进行性肺部炎症及最终的脓毒症密切相关。越来越多的证据表明，儿童时期普遍接种的减毒活疫苗也具有有益的非特异性免疫作用，包括降低因无关感染导致的死亡率和住院率。有人提出，减毒活疫苗相关的非特异性作用是诱导训练有素的固有免疫更有效地抵抗更广泛感染的结果。为此，我们实验室报告称，用减毒活真菌菌株免疫可诱导一种新型的训练有素的固有免疫，通过髓系来源的抑制细胞为小鼠提供针对各种脓毒症诱导物的保护。因此，我们在大新奥尔良地区的医护人员中开展了一项使用减毒活麻疹、腮腺炎、风疹（MMR）疫苗的随机对照临床试验，旨在预防/减轻与新冠病毒感染相关的严重肺部炎症/脓毒症（ClinicalTrials.gov标识符：NCT04475081）。其中一个结果是评估接种MMR疫苗与安慰剂的人群血液中的髓系来源抑制细胞群体。在MMR临床试验期间，几种新冠病毒疫苗意外获得紧急批准，这使得无法研究MMR疫苗对新冠病毒感染相关健康状况的影响。不幸的是，由于一些固有局限性（血液白细胞百分比低、样本量小），我们也无法显示MMR疫苗对外周血髓系来源抑制细胞有任何影响，这些局限性还包括与密苏里州圣路易斯的一项类似试验（皇冠加冕试验；ClinicalTrials.gov标识符：NCT04333732）的合作。相比之下，对试验参与者的新冠病毒疫苗反应监测显示，接种MMR疫苗的人比接种安慰剂的人更常出现高新冠病毒抗体滴度。虽然该试验在很大程度上没有定论，但从应对几个与试验相关的挑战中吸取的经验教训可能有助于未来测试减毒活疫苗非特异性有益免疫作用的研究。
