Jalah Rashmi, Kulkarni Viraj, Patel Vainav, Rosati Margherita, Alicea Candido, Bear Jenifer, Yu Lei, Guan Yongjun, Shen Xiaoying, Tomaras Georgia D, LaBranche Celia, Montefiori David C, Prattipati Rajasekhar, Pinter Abraham, Bess Julian, Lifson Jeffrey D, Reed Steven G, Sardesai Niranjan Y, Venzon David J, Valentin Antonio, Pavlakis George N, Felber Barbara K
Human Retrovirus Pathogenesis Section, National Cancer Institute, Frederick, Maryland, United States of America.
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Frederick, Maryland, United States of America.
PLoS One. 2014 Mar 13;9(3):e91550. doi: 10.1371/journal.pone.0091550. eCollection 2014.
We tested the concept of combining DNA with protein to improve anti-HIV Env systemic and mucosal humoral immune responses. Rhesus macaques were vaccinated with DNA, DNA&protein co-immunization or DNA prime followed by protein boost, and the magnitude and mucosal dissemination of the antibody responses were monitored in both plasma and mucosal secretions. We achieved induction of robust humoral responses by optimized DNA vaccination delivered by in vivo electroporation. These responses were greatly increased upon administration of a protein boost. Importantly, a co-immunization regimen of DNA&protein injected in the same muscle at the same time induced the highest systemic binding and neutralizing antibodies to homologous or heterologous Env as well as the highest Env-specific IgG in saliva. Inclusion of protein in the vaccine resulted in more immunized animals with Env-specific IgG in rectal fluids. Inclusion of DNA in the vaccine significantly increased the longevity of systemic humoral immune responses, whereas protein immunization, either as the only vaccine component or as boost after DNA prime, was followed by a great decline of humoral immune responses overtime. We conclude that DNA&protein co-delivery in a simple vaccine regimen combines the strength of each vaccine component, resulting in improved magnitude, extended longevity and increased mucosal dissemination of the induced antibodies in immunized rhesus macaques.
我们测试了将DNA与蛋白质相结合以改善抗HIV Env全身和黏膜体液免疫反应的概念。对恒河猴进行DNA疫苗接种、DNA与蛋白质联合免疫或DNA初免后再进行蛋白质加强免疫，并在血浆和黏膜分泌物中监测抗体反应的强度和黏膜扩散情况。通过体内电穿孔进行优化的DNA疫苗接种，我们成功诱导了强烈的体液免疫反应。给予蛋白质加强免疫后，这些反应大幅增强。重要的是，将DNA与蛋白质同时注射到同一肌肉中的联合免疫方案诱导产生了针对同源或异源Env的最高全身结合抗体和中和抗体，以及唾液中最高的Env特异性IgG。疫苗中包含蛋白质使得更多免疫动物的直肠液中出现Env特异性IgG。疫苗中包含DNA显著延长了全身体液免疫反应的持续时间，而蛋白质免疫，无论是作为唯一的疫苗成分还是在DNA初免后作为加强免疫，随着时间的推移体液免疫反应都会大幅下降。我们得出结论，在一个简单的疫苗方案中同时递送DNA和蛋白质，结合了每种疫苗成分的优势，导致在免疫的恒河猴中诱导产生的抗体强度提高、持续时间延长以及黏膜扩散增加。
