Impaired Antibody-mediated Protection and Defective IgA B-Cell Memory in Experimental Infection of Adults with Respiratory Syncytial Virus
Maximillian S. Habibi, Agnieszka Jozwik, Spyridon Makris, Jake Dunning, Allan Paras, John P. DeVincenzo, Cornelis A. M. de Haan, Jens Wrammert, Peter J. M. Openshaw, and Christopher Chiu
American Journal of Respiratory and Critical Care Medicine, Vol. 191, No. 9 (2015), pp. 1040-1049.
イギリスからの報告．
＜背景＞
ＲＳウイルスは生涯を通して再感染する．
４０年以上研究されているがワクチンはなく，防御機能はよくわかっていない．
最近のＲＳウイルスワクチン候補物質はＲＳＶ特異的血清中和抗体を強く誘導し観察研究ではＲＳウイルス関連の入院を減少させるが，
実際には感染を防げないかもしれない．
＜目的＞
感染からの防御とＲＳウイルス特異的液性免疫記憶の生成との相互関係を明らかにし，効果的なワクチンの開発につなげる．
＜方法＞
健康成人に生きたＲＳウイルスを接種し，感染からの防御を血清と粘液抗体にて調べた．
ＲＳウイルス特異的血清形質芽球とメモリーＢ細胞の割合と抗体の寿命について解析した．
＜結果＞
もともと持っている血清抗体は比較的高いにもかかわらず，３４名（５６％）が感染し，そのうち２３名（６８％）は風邪症状を呈した．
もともとの鼻のＲＳウイルス特異的ＩｇＡが血清の中和抗体よりもＰＣＲで確定した感染と強く相関していた．
感染者のウイルス特異的抗体の力価は変動し一過性であったが，１０日目にピークをもつ形質芽球と相関した．
回復期の間，ＲＳウイルス特異的メモリーＢ細胞のＩｇＧ（ＩｇＡではない）のみが血中で検出された．
これはインフルエンザの自然感染（ウイルス特異的ＩｇＡメモリーＢ細胞が検出）とは対照的であった．
＜感想＞
ＲＳウイルス感染においてはＩｇＡのメモリーＢ細胞が検出されず，このため何回も感染をくりかえすのかもしれないようです．
ウイルスの侵入は粘膜からなので，血中よりは鼻粘膜のＩｇＡを効果的に誘導することがワクチンには必要なようです．
Rationale: Despite relative antigenic stability, respiratory syncytial virus (RSV) reinfects throughout life. After more than 40 years of research, no effective human vaccine exists and correlates of protection remain poorly defined. Most current vaccine candidates seek to induce high levels of RSV-specific serum neutralizing antibodies, which are associated with reduced RSV-related hospitalization rates in observational studies but may not actually prevent infection.
Objectives: To characterize correlates of protection from infection and the generation of RSV-specific humoral memory to promote effective vaccine development.
Methods: We inoculated 61 healthy adults with live RSV and studied protection from infection by serum and mucosal antibody. We analyzed RSV-specific peripheral blood plasmablast and memory B-cell frequencies and antibody longevity.
Measurements and Main Results: Despite moderately high levels of preexisting serum antibody, 34 (56%) became infected, of whom 23 (68%) developed symptomatic colds. Prior RSV-specific nasal IgA correlated significantly more strongly with protection from polymerase chain reaction–confirmed infection than serum neutralizing antibody. Increases in virus-specific antibody titers were variable and transient in infected subjects but correlated with plasmablasts that peaked around Day 10. During convalescence, only IgG (and no IgA) RSV-specific memory B cells were detectable in peripheral blood. This contrasted with natural influenza infection, in which virus-specific IgA memory B cells were readily recovered.
Conclusions: This observed specific defect in IgA memory may partly explain the ability of RSV to cause recurrent symptomatic infections. If so, vaccines able to induce durable RSV-specific IgA responses may be more protective than those generating systemic antibody alone.
Read More: http://www.atsjournals.org/doi/abs/10.1164/rccm.201412-2256OC#.VWusX6ww-Hw