Chege Gerald K, Burgers Wendy A, Müller Tracey L, Gray Clive M, Shephard Enid G, Barnett Susan W, Ferrari Guido, Montefiori David, Williamson Carolyn, Williamson Anna-Lise
Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Vaccine. 2017 Feb 7;35(6):929-937. doi: 10.1016/j.vaccine.2016.12.060. Epub 2017 Jan 6.
Successful future HIV vaccines are expected to generate an effective cellular and humoral response against the virus in both the peripheral blood and mucosal compartments. We previously reported the development of DNA-C and MVA-C vaccines based on HIV-1 subtype C and demonstrated their immunogenicity when given in a DNA prime-MVA boost combination in a nonhuman primate model. In the current study, rhesus macaques previously vaccinated with a DNA-C and MVA-C vaccine regimen were re-vaccinated 3.5years later with MVA-C followed by a protein vaccine based on HIV-1 subtype C envelope formulated with MF59 adjuvant (gp140Env/MF59), and finally a concurrent boost with both vaccines. A single MVA-C re-vaccination elicited T cell responses in all animals similar to previous peak responses, with 4/7 demonstrating responses >1000 SFU/10 PBMC. In contrast to an Env/MF59-only vaccine, concurrent boosting with MVA-C and Env/MF59 induced HIV-specific cellular responses in multiple mucosal associated lymph nodes in 6/7 animals, with high magnitude responses in some animals. Both vaccine regimens induced high titer Env-specific antibodies with ADCC activity, as well as neutralization of Tier 1 viruses and modest Tier 2 neutralization. These data demonstrate the feasibility of inducing HIV-specific immunity in the blood and mucosal sites of viral entry by means of DNA and poxvirus-vectored vaccines, in combination with a HIV envelope-based protein vaccine.
未来成功的HIV疫苗有望在外周血和黏膜部位对该病毒产生有效的细胞和体液免疫反应。我们之前报道了基于HIV-1 C亚型的DNA-C和MVA-C疫苗的研发，并在非人灵长类动物模型中以DNA初免-MVA加强的组合方式给药时证明了它们的免疫原性。在当前研究中，先前接种过DNA-C和MVA-C疫苗方案的恒河猴在3.5年后再次接种MVA-C，随后接种基于HIV-1 C亚型包膜并与MF59佐剂配制的蛋白疫苗（gp140Env/MF59），最后同时用两种疫苗进行加强免疫。单次MVA-C再次接种在所有动物中均引发了T细胞反应，类似于之前的峰值反应，7只中有4只的反应>1000 SFU/10 PBMC。与仅使用Env/MF59的疫苗不同，MVA-C与Env/MF59同时加强免疫在7只动物中的6只的多个黏膜相关淋巴结中诱导了HIV特异性细胞反应，一些动物的反应强度很高。两种疫苗方案均诱导了具有ADCC活性的高滴度Env特异性抗体，以及对1级病毒的中和作用和对2级病毒的适度中和作用。这些数据证明了通过DNA和痘病毒载体疫苗，结合基于HIV包膜的蛋白疫苗，在血液和病毒进入的黏膜部位诱导HIV特异性免疫的可行性。
