Human Antibody Responses Following Vaccinia Immunization Using Protein Microarrays and Correlation With Cell-Mediated Immunity and Antibody-Dependent Cellular Cytotoxicity Responses

被引:13
作者
Frey, Sharon E. [1 ]
Stapleton, Jack T. [2 ,3 ]
Ballas, Zuhair K. [2 ,3 ]
Rasmussen, Wendy L. [2 ,3 ]
Kaufman, Thomas M. [2 ,3 ]
Blevins, Tammy P. [1 ]
Jensen, Travis L. [4 ]
Davies, D. Huw [5 ]
Tary-Lehmann, Magdalena [6 ]
Chaplin, Paul [7 ]
Hill, Heather [4 ]
Goll, Johannes B. [4 ]
机构
[1] St Louis Univ, Dept Internal Med, Sch Med, 11003 Grand Blvd,DRC 8, St Louis, MO 63104 USA
[2] Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA
[3] Iowa City VA Med Ctr, Iowa City, IA 52242 USA
[4] Emmes, Rockville, MD USA
[5] Univ Calif Irvine, Vaccine Res & Dev Ctr, Sch Med, Dept Physiol & Biophys, Irvine, CA USA
[6] Cellular Technol Ltd, Shaker Hts, OH USA
[7] Bavarian Nordic, Martinsried, Germany
基金
美国国家卫生研究院;
关键词
MVA vaccine; modified vaccinia Ankara; smallpox; vaccinia western reserve; ADCC; ELISPOT; antibody responses; protein microarray; correlation of protection; membrane proteins; SMALLPOX VACCINATION; VIRUS ANKARA; MVA; IMMUNOGENICITY; SAFETY; SULFATE; BINDS;
D O I
10.1093/infdis/jiab111
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. There are limited data regarding immunological correlates of protection for the modified vaccinia Ankara (MVA) smallpox vaccine. Methods. A total of 523 vaccinia-naive subjects were randomized to receive 2 vaccine doses, as lyophilized MVA given subcutaneously, liquid MVA given subcutaneously (liquid-SC group), or liquid MVA given intradermally (liquid-ID group) 28 days apart. For a subset of subjects, antibody-dependent cellular cytotoxicity (ADCC), interferon-gamma release enzyme-linked immunospot (ELISPOT), and protein microarray antibody-binding assays were conducted. Protein microarray responses were assessed for correlations with plaque reduction neutralization titer (PRNT), enzyme-linked immunosorbent assay, ADCC, and ELISPOT results. Results. MVA elicited significant microarray antibody responses to 15 of 224 antigens, mostly virion membrane proteins, at day 28 or 42, particularly WR113/D8L and WR101H3L. In the liquid-SC group, responses to 9 antigens, including WR113/D8L and WR101/H3L, correlated with PRNT results. Three were correlated in the liquid-ID group. No significant correlations were observed with ELISPOT responses. In the liquid-ID group, WR052/F13L, a membrane glycoprotein, correlated with ADCC responses. Conclusions. MVA elicited antibodies to 15 vaccinia strain antigens representing virion membrane. Antibody responses to 2 proteins strongly increased and significantly correlated with increases in PRNT. Responses to these proteins are potential correlates of protection and may serve as immunogens for future vaccine development.
引用
收藏
页码:1372 / 1382
页数:11
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