Chege Gerald K, Shephard Enid G, Meyers Ann, van Harmelen Joanne, Williamson Carolyn, Lynch Alisson, Gray Clive M, Rybicki Edward P, Williamson Anna-Lise
Institute of Primate Research, PO Box 24481, Karen 00502, Nairobi, Kenya.
Medical Virology, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, University of Cape Town, Rondebosch, Cape Town, South Africa.
J Gen Virol. 2008 Sep;89(Pt 9):2214-2227. doi: 10.1099/vir.0.83501-0.
A DNA vaccine expressing human immunodeficiency virus type 1 (HIV-1) southern African subtype C Gag (pTHGag) and a recombinant baculovirus Pr55gag virus-like particle prepared using a subtype C Pr55gag protein (Gag VLP) was tested in a prime-boost inoculation regimen in Chacma baboons. The response of five baboons to Gag peptides in a gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assay after three pTHGag immunizations ranged from 100 to 515 spot-forming units (s.f.u.) per 10(6) peripheral blood mononuclear cells (PBMCs), whilst the response of two baboons to the Gag VLP vaccine ranged from 415 to 465 s.f.u. per 10(6) PBMCs. An increase in the Gag-specific response to a range of 775-3583 s.f.u. per 10(6) PBMCs was achieved by boosting with Gag VLPs the five baboons that were primed with pTHGag. No improvement in Gag responses was achieved in this prime-boost inoculation regimen by increasing the number of pTHGag inoculations to six. IFN-gamma responses were mapped to several peptides, some of which have been reported to be targeted by PBMCs from HIV-1 subtype C-infected individuals. Gag VLPs, given as a single-modality regimen, induced a predominantly CD8+ T-cell IFN-gamma response and interleukin-2 was a major cytokine within a mix of predominantly Th1 cytokines produced by a DNA-VLP prime-boost modality. The prime-boost inoculation regimen induced high serum p24 antibody titres in all baboons, which were several fold above that induced by the individual vaccines. Overall, this study demonstrated that these DNA prime/VLP boost vaccine regimens are highly immunogenic in baboons, inducing high-magnitude and broad multifunctional responses, providing support for the development of these products for clinical trials.
一种表达1型人类免疫缺陷病毒（HIV-1）南非C亚型Gag的DNA疫苗（pTHGag）和一种使用C亚型Pr55gag蛋白制备的重组杆状病毒Pr55gag病毒样颗粒（Gag VLP），在查卡马狒狒中进行了初免-加强接种方案测试。三只狒狒在三次pTHGag免疫后，在γ干扰素（IFN-γ）酶联免疫斑点（ELISPOT）试验中对Gag肽的反应范围为每10⁶外周血单个核细胞（PBMC）100至515个斑点形成单位（s.f.u.），而两只狒狒对Gag VLP疫苗的反应范围为每10⁶ PBMC 415至465个s.f.u.。通过用Gag VLPs加强免疫以pTHGag初免的三只狒狒，使其对Gag的特异性反应增加到每10⁶ PBMC 775 - 3583个s.f.u.的范围。在该初免-加强接种方案中，将pTHGag接种次数增加到六次并未使Gag反应得到改善。IFN-γ反应被定位到几种肽上，其中一些据报道是来自HIV-1 C亚型感染个体的PBMC的靶向目标。作为单一模式方案给予的Gag VLPs诱导了主要为CD8⁺ T细胞的IFN-γ反应，并且白细胞介素-2是由DNA-VLP初免-加强模式产生的主要为Th1细胞因子混合物中的主要细胞因子。初免-加强接种方案在所有狒狒中诱导了高血清p24抗体滴度，比单个疫苗诱导的滴度高几倍。总体而言，本研究表明这些DNA初免/VLP加强疫苗方案在狒狒中具有高度免疫原性，诱导了高强度和广泛的多功能反应，为这些产品用于临床试验的开发提供了支持。
