ADCC-activating antibodies correlate with decreased risk of congenital human cytomegalovirus transmission.
ADCC-activating antibodies correlate with decreased risk of congenital human cytomegalovirus transmission.
复制标题
DOI：
10.1172/jci.insight.167768
复制
发表时间：
2023-07-10
期刊：
影响因子：
8
通讯作者：
Permar, Sallie R.
中科院分区：
文献类型：
--
作者：
Semmes, Eleanor C.;Miller, Itzayana G.;Rodgers, Nicole;Phan, Caroline T.;Hurst, Jillian H.;Walsh, Kyle M.;Stanton, Richard J.;Pollara, Justin;Permar, Sallie R.
人类巨细胞病毒（HCMV）是世界上最常见的垂直传播感染，但目前还没有疫苗或治疗方法来预防先天性HCMV （cCMV）感染。新出现的证据表明，抗体Fc效应功能可能是以前未被重视的母体抗HCMV免疫的组成部分。我们最近报道了抗体依赖性细胞吞噬（ADCP）和FcγRI/FcγRII的IgG活化与抗cCMV传播的保护有关，这使我们假设额外的fc介导的抗体功能可能很重要。在同样的hcmv传播组（n = 41）和非hcmv传播组（n = 40）中，研究人员发现，母体血清抗体依赖性细胞毒性（ADCC）激活程度越高，cCMV传播风险越低。我们研究了ADCC和IgG对9种病毒抗原的反应之间的关系，发现ADCC的激活与血清中IgG与HCMV免疫逃避蛋白UL16的结合密切相关。此外，我们确定更高的ul16特异性IgG结合和FcγRIII/CD16结合与cCMV传播风险的最大降低相关。我们的研究结果表明，针对UL16等靶点的adcc激活抗体可能代表了针对cCMV感染的重要保护性母体免疫反应，可以指导未来HCMV相关研究以及基于疫苗或抗体的治疗开发。
Human cytomegalovirus (HCMV) is the most common vertically transmitted infection worldwide, yet there are no vaccines or therapeutics to prevent congenital HCMV (cCMV) infection. Emerging evidence indicates that antibody Fc effector functions may be a previously underappreciated component of maternal immunity against HCMV. We recently reported that antibody-dependent cellular phagocytosis (ADCP) and IgG activation of FcγRI/FcγRII were associated with protection against cCMV transmission, leading us to hypothesize that additional Fc-mediated antibody functions may be important. In this same cohort of HCMV-transmitting (n = 41) and nontransmitting (n = 40) mother-infant dyads, we report that higher maternal sera antibody–dependent cellular cytotoxicity (ADCC) activation is also associated with lower risk of cCMV transmission. We investigated the relationship between ADCC and IgG responses against 9 viral antigens and found that ADCC activation correlated most strongly with sera IgG binding to the HCMV immunoevasin protein UL16. Moreover, we determined that higher UL16-specific IgG binding and FcγRIII/CD16 engagement were associated with the greatest risk reduction in cCMV transmission. Our findings indicate that ADCC-activating antibodies against targets such as UL16 may represent an important protective maternal immune response against cCMV infection that can guide future HCMV correlates studies and vaccine or antibody-based therapeutic development.
登录
查看更多内容
影响因子：
5.5
作者：
Bernstein DI;Munoz FM;Callahan ST;Rupp R;Wootton SH;Edwards KM;Turley CB;Stanberry LR;Patel SM;Mcneal MM;Pichon S;Amegashie C;Bellamy AR
通讯作者：
Bellamy AR
DOI：
10.1073/pnas.1800177115
发表时间：
2018-06-12
影响因子：
11.1
作者：
Nelson, Cody S.;Huffman, Tori;Permar, Sallie R.
通讯作者：
Permar, Sallie R.
影响因子：
7.7
作者：
Fielding, Ceri A.;Weekes, Michael P.;Wilkinson, Gavin W. G.
通讯作者：
Wilkinson, Gavin W. G.
影响因子：
5.4
作者：
McSharry, Brian P.;Burgert, Hans-Gerhard;Wilkinson, Gavin W. G.
通讯作者：
Wilkinson, Gavin W. G.
影响因子：
32.4
作者：
Cosman, D;Müllberg, J;Chalupny, NJ
通讯作者：
Chalupny, NJ