Vaccination with a replication-defective cytomegalovirus vaccine elicits a glycoprotein B-specific monoclonal antibody repertoire distinct from natural infection.
Vaccination with a replication-defective cytomegalovirus vaccine elicits a glycoprotein B-specific monoclonal antibody repertoire distinct from natural infection.
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DOI：
10.1038/s41541-023-00749-0
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发表时间：
2023-10-10
期刊：
影响因子：
9.2
通讯作者：
中科院分区：
文献类型：
--
作者：
人巨细胞病毒(HCMV)是全球主要的先天性传染病，也是移植受者最常见的病毒感染，因此寻找一种针对HCMV的疫苗是当务之急。体液免疫与HCMV感染的保护作用相关。迄今为止测试的最有效的疫苗是由糖蛋白B蛋白和水包油乳剂佐剂MF59组成的，它使人巨细胞病毒的获得率减少了50%。我们对从接种了失效的传染性单周期(CDV)巨细胞病毒疫苗V160的个体分离的GB特异性单抗进行了表征，并将这些抗体与从自然感染的个体分离的GB特异性单抗进行了比较。我们发现，与自然感染分离的抗体不同，V160疫苗可以产生与细胞表面表达的GB均匀结合的GB特异性抗体，而天然感染的抗体则可变地结合到细胞相关的GB上。接种疫苗可产生类似广度的gb特异性抗体，与gb基因1-5型的结合谱与自然感染相当。从V160疫苗接种者中分离到的GB特异性中和抗体很少，与自然感染者相比，具有可识别的GB抗原域特异性的抗体更少。我们还发现Gb残基N73的糖基化可能会屏蔽Gb特异性抗体的结合。
Human Cytomegalovirus (HCMV) is the leading infectious congenital infection globally and the most common viral infection in transplant recipients, therefore identifying a vaccine for HCMV is a top priority. Humoral immunity is a correlate of protection for HCMV infection. The most effective vaccine tested to date, which achieved 50% reduction in acquisition of HCMV, was comprised of the glycoprotein B protein given with an oil-in-water emulsion adjuvant MF59. We characterize gB-specific monoclonal antibodies isolated from individuals vaccinated with a disabled infectious single cycle (DISC) CMV vaccine, V160, and compare these to the gB-specific monoclonal antibody repertoire isolated from naturally-infected individuals. We find that vaccination with V160 resulted in gB-specific antibodies that bound homogenously to gB expressed on the surface of a cell in contrast to antibodies isolated from natural infection which variably bound to cell-associated gB. Vaccination resulted in a similar breadth of gB-specific antibodies, with binding profile to gB genotypes 1–5 comparable to that of natural infection. Few gB-specific neutralizing antibodies were isolated from V160 vaccinees and fewer antibodies had identifiable gB antigenic domain specificity compared to that of naturally-infected individuals. We also show that glycosylation of gB residue N73 may shield binding of gB-specific antibodies.
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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
影响因子：
8.8
作者：
Nebbia, G.;Mattes, F. M.;Emery, V. C.
通讯作者：
Emery, V. C.
影响因子：
4.2
作者：
Das R;Blazquez-Gamero D;Bernstein DI;Gantt S;Bautista O;Beck K;Conlon A;Rosenbloom D;Wang D;Ritter M;Arnold B;Annunziato P;Russell K
通讯作者：
Russell K
DOI：
10.1093/infdis/jiy102
发表时间：
2018-05-25
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Baraniak I;Kropff B;McLean GR;Pichon S;Piras-Douce F;Milne RSB;Smith C;Mach M;Griffiths PD;Reeves MB
通讯作者：
Reeves MB
影响因子：
8.8
作者：
Pass, Robert F.
通讯作者：
Pass, Robert F.