Akkaya Munir, Akkaya Billur, Sheehan Patrick W, Miozzo Pietro, Pena Mirna, Qi Chen-Feng, Manzella-Lapeira Javier, Bolland Silvia, Pierce Susan K
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA.
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Eur J Immunol. 2017 Nov;47(11):1890-1899. doi: 10.1002/eji.201747113. Epub 2017 Aug 21.
The development of vaccines for infectious diseases for which we currently have none, including HIV, will likely require the use of adjuvants that strongly promote germinal center responses and somatic hypermutation to produce broadly neutralizing antibodies. Here we compared the outcome of immunization with the T-cell dependent antigen, NP-conjugated to chicken gamma globulin (NP-CGG) adjuvanted with the toll-like receptor 9 (TLR9) ligands, CpG-A or CpG-B, alone or conjugated with the cationic lipid carrier, DOTAP. We provide evidence that only NP-CGG adjuvanted with DOTAP-CpG-B was an effective vaccine in mice resulting in robust germinal center responses, isotype switching and high affinity NP-specific antibodies. The effectiveness of DOTAP-CpG-B as an adjuvant was dependent on the expression of the TLR9 signaling adaptor MyD88 in immunized mice. These results indicate DOTAP-CpG-B but not DOTAP-CpG-A is an effective adjuvant for T cell-dependent protein antigen-based vaccines.
开发针对包括艾滋病病毒在内的目前尚无疫苗的传染病疫苗，可能需要使用能强力促进生发中心反应和体细胞超突变以产生广泛中和抗体的佐剂。在此，我们比较了用与鸡γ球蛋白偶联的T细胞依赖性抗原NP（NP-CGG）免疫的结果，该抗原单独用Toll样受体9（TLR9）配体CpG-A或CpG-B佐剂，或与阳离子脂质载体DOTAP偶联。我们提供的证据表明，仅用DOTAP-CpG-B佐剂的NP-CGG在小鼠中是一种有效的疫苗，可产生强大的生发中心反应、同种型转换和高亲和力的NP特异性抗体。DOTAP-CpG-B作为佐剂的有效性取决于免疫小鼠中TLR9信号衔接蛋白MyD88的表达。这些结果表明，DOTAP-CpG-B而非DOTAP-CpG-A是基于T细胞依赖性蛋白质抗原的疫苗的有效佐剂。
