Ren Dabin, Murphy Timothy F, Lafontaine Eric R, Pichichero Michael E
Rochester General Hospital Research Institute, Rochester, NY, United States.
Clinical and Translational Research Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, United States.
Front Immunol. 2017 Aug 11;8:953. doi: 10.3389/fimmu.2017.00953. eCollection 2017.
() is a prominent mucosal pathogen causing acute otitis media (AOM). We studied nasopharyngeal (NP) colonization, AOM frequency and mucosal antibody responses to four vaccine candidate proteins: outer membrane protein (OMP) CD, oligopeptide permease (Opp) A, hemagglutinin (Hag), and Pilin A clade 2 (PilA2) from stringently defined otitis prone (sOP) children, who experience the greatest burden of disease, compared to non-otitis prone (NOP) children. sOP children had higher NP colonization of (30 vs. 22%, = 0.0003) and -caused AOM rates (49 vs. 24%, < 0.0001) than NOP children. Natural acquisition of mucosal antibodies to proteins OMP CD (IgG, < 0.0001), OppA (IgG, = 0.018), Hag (IgG and IgA, both < 0.0001), and PilA2 (IgA, < 0.0001) was lower in sOP than NOP children. Higher levels of mucosal IgG to Hag ( = 0.039) and PilA2 ( = 0.0076), and IgA to OMP CD ( = 0.010), OppA ( = 0.030), and PilA2 ( = 0.043) were associated with lower carriage of in NOP but not sOP children. Higher levels of mucosal IgG to OMP CD ( = 0.0070) and Hag ( = 0.0003), and IgA to Hag ( = 0.0067) at asymptomatic colonization than those at onset of AOM were associated with significantly lower rate of NP colonization progressing to AOM in NOP compared to sOP children (3 vs. 26%, < 0.0001). In conclusion, sOP children had a diminished mucosal antibody response to proteins, which was associated with higher frequencies of asymptomatic NP colonization and NP colonization progressing to -caused AOM. Enhancing antigen-specific mucosal immune responses to levels higher than achieved by natural exposure will be necessary to prevent AOM in sOP children.
（）是引起急性中耳炎（AOM）的一种主要黏膜病原体。我们研究了来自严格定义的易患中耳炎（sOP）儿童（这些儿童疾病负担最重）与非易患中耳炎（NOP）儿童相比，鼻咽（NP）定植情况、AOM发生率以及对四种候选疫苗蛋白的黏膜抗体反应：外膜蛋白（OMP）CD、寡肽通透酶（Opp）A、血凝素（Hag）和来自2进化枝的菌毛蛋白A（PilA2）。与NOP儿童相比，sOP儿童的NP定植率更高（30%对22%，P = 0.0003），且由（）引起的AOM发生率更高（49%对24%，P < 0.0001）。与NOP儿童相比，sOP儿童对OMP CD蛋白（IgG，P < 0.0001）、OppA（IgG，P = 0.018）、Hag（IgG和IgA，均P < 0.0001）和PilA2（IgA，P < 0.0001）的黏膜抗体自然获得水平较低。在NOP儿童而非sOP儿童中，较高水平的针对Hag（P = 0.039）和PilA2（P = 0.0076）的黏膜IgG，以及针对OMP CD（P = 0.010）、OppA（P = 0.030）和PilA2（P = 0.043）的IgA与（）的携带率较低相关。与AOM发作时相比，无症状定植时较高水平的针对OMP CD（P = 0.0070）和Hag（P = 0.0003）的黏膜IgG，以及针对Hag（P = 0.0067）的IgA与NOP儿童中（）的NP定植进展为AOM的发生率显著较低相关，而sOP儿童中该发生率为3%对26%，P < 0.0001。总之，sOP儿童对（）蛋白的黏膜抗体反应减弱，这与无症状NP定植频率较高以及NP定植进展为（）引起的AOM相关。为预防sOP儿童发生AOM，有必要将（）抗原特异性黏膜免疫反应增强至高于自然暴露所达到的水平。
