Ren Dabin, Almudevar Anthony L, Murphy Timothy F, Lafontaine Eric R, Campagnari Anthony A, Luke-Marshall Nicole, Casey Janet R, Pichichero Michael E
Rochester General Hospital Research Institute, Rochester, NY 14621, USA.
Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Vaccine. 2015 Oct 26;33(43):5809-5814. doi: 10.1016/j.vaccine.2015.09.023. Epub 2015 Sep 21.
There is no licensed vaccine for Moraxella catarrhalis (Mcat), which is a prominent bacterium causing acute otitis media (AOM) in children and lower respiratory tract infections in adults. Nasopharyngeal (NP) colonization caused by respiratory bacteria results in natural immunization of the host. To identify Mcat antigens as vaccine candidates, we evaluated the development of naturally induced antibodies to 5 Mcat surface proteins in children 6-30 months of age during Mcat NP colonization and AOM.
Human serum IgG against the recombinant Mcat proteins, outer membrane protein (OMP) CD, oligopeptide permease (Opp)A, hemagglutinin (Hag), Moraxella surface protein (Msp)22, and PilA clade 2 (PilA2) was quantitated by using an ELISA assay.
There were 223 Mcat NP colonization episodes documented in 111 (60%) of 184 children in the study. Thirty five Mcat AOM episodes occurred in 30 (16%) of 184 children. All 5 Mcat candidate vaccine antigens evaluated stimulated a significant rise in serum IgG levles over time from 6 to 36 months of age (P<0.001), with a rank order as follows: Msp22=OppA>OMP CD=Hag=PilA2. Children with no detectable Mcat NP colonization showed a higher serum IgG level against OppA, Hag, and Msp22 compared to those with Mcat NP colonization (P<0.05). Individual data showed that some children responded to AOM with an antibody increase to one or more of the studied Mcat proteins but some children failed to respond.
Serum antibody to Mcat candidate vaccine proteins OMP CD, OppA, Msp22, Hag, and PilA2 increased with age in naturally immunized children age 6-30 months following Mcat NP colonization and AOM. High antibody levels against OppA, Msp22, and Hag correlated with reduced carriage. The results support further investigation of these vaccine candidates in protecting against Mcat colonization and infection.
卡他莫拉菌(Mcat)尚无获批疫苗,该菌是导致儿童急性中耳炎(AOM)及成人下呼吸道感染的一种主要细菌。呼吸道细菌引起的鼻咽(NP)定植可使宿主自然免疫。为鉴定Mcat抗原作为候选疫苗,我们评估了6至30月龄儿童在Mcat NP定植和AOM期间针对5种Mcat表面蛋白自然诱导抗体的产生情况。
采用酶联免疫吸附测定(ELISA)法对针对重组Mcat蛋白、外膜蛋白(OMP)CD、寡肽通透酶(Opp)A、血凝素(Hag)、莫拉菌表面蛋白(Msp)22和菌毛A进化枝2(PilA2)的人血清IgG进行定量。
该研究中184名儿童中有111名(60%)记录到223次Mcat NP定植事件。184名儿童中有30名(16%)发生了35次Mcat AOM事件。所评估的全部5种Mcat候选疫苗抗原均刺激血清IgG水平在6至36月龄期间随时间显著升高(P<0.001),排序如下:Msp22 = OppA>OMP CD = Hag = PilA2。与有Mcat NP定植的儿童相比,未检测到Mcat NP定植的儿童针对OppA、Hag和Msp22的血清IgG水平更高(P<0.05)。个体数据显示,一些儿童对AOM的反应是针对一种或多种所研究的Mcat蛋白的抗体增加,但一些儿童无反应。
在Mcat NP定植和AOM后,6至30月龄自然免疫儿童中针对Mcat候选疫苗蛋白OMP CD、OppA、Msp22、Hag和PilA2的血清抗体随年龄增加。针对OppA、Msp22和Hag的高抗体水平与携带率降低相关。这些结果支持进一步研究这些候选疫苗在预防Mcat定植和感染方面的作用。