Chin'ombe Nyasha, Bourn William R, Williamson Anna-Lise, Shephard Enid G
Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory 7925, Cape Town, South Africa.
Virol J. 2009 Jun 25;6:87. doi: 10.1186/1743-422X-6-87.
Recombinant Salmonella vaccine vectors may potentially be used to induce specific CD4+ T cell responses against foreign viral antigens. Such immune responses are required features of vaccines against pathogens such as human immunodeficiency virus type 1 (HIV-1). The aim of this study was to investigate the induction of systemic HIV-1-specific CD4+ T helper (Th) responses in mice after oral immunization with a live attenuated Salmonella vaccine vector that expressed HIV-1 subtype C Gag. Groups of BALB/c mice were vaccinated orally three times (4 weeks apart) with this recombinant Salmonella. At sacrifice, 28 days after the last immunization, systemic CD4+ Th1 and Th2 cytokine responses were evaluated by enzyme-linked immunospot assay and cytometric bead array. HIV-1 Gag-specific IgG1 and IgG2a humoral responses in the serum were determined by enzyme-linked immunosorbent assay.
Mice vaccinated with the recombinant Salmonella elicited both HIV-1-specific Th1 (interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha)) and Th2 (interleukin-4 (IL-4) and interleukin-5 (IL-5)) cytokine responses. The vaccine induced 70 (IFN-gamma) spot-forming units (SFUs)/10e(6) splenocytes and 238 IL-4 SFUs/10e(6) splenocytes. Splenocytes from vaccinated mice also produced high levels of Th1 and Th2 cytokines upon stimulation with a Gag CD4 peptide. The levels of IFN-gamma, TNF-alpha, IL-4 and IL-5 were 7.5-, 29.1-, 26.2- and 89.3-fold above the background, respectively. Both HIV-1 Gag-specific IgG1 and IgG2a antibodies were detected in the sera of vaccinated mice.
The study highlights the potential of orally-delivered attenuated Salmonella as mucosal vaccine vectors for HIV-1 Subtype C Gag to induce Gag-specific CD4+ Th1 and Th2 cellular immune responses and antibodies which may be important characteristics required for protection against HIV-1 infection.
重组沙门氏菌疫苗载体可能可用于诱导针对外源病毒抗原的特异性CD4+ T细胞应答。此类免疫应答是针对诸如1型人类免疫缺陷病毒（HIV-1）等病原体的疫苗所必需的特性。本研究的目的是调查用表达HIV-1 C亚型Gag的减毒活沙门氏菌疫苗载体经口免疫小鼠后，全身性HIV-1特异性CD4+ T辅助（Th）应答的诱导情况。将BALB/c小鼠分组，用这种重组沙门氏菌经口免疫三次（间隔4周）。在末次免疫后28天处死小鼠时，通过酶联免疫斑点测定法和细胞计数珠阵列评估全身性CD4+ Th1和Th2细胞因子应答。通过酶联免疫吸附测定法测定血清中HIV-1 Gag特异性IgG1和IgG2a体液应答。
用重组沙门氏菌免疫的小鼠引发了HIV-1特异性Th1（干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α））和Th2（白细胞介素-4（IL-4）和白细胞介素-5（IL-5））细胞因子应答。该疫苗诱导出70个（IFN-γ）斑点形成单位（SFU）/10e(6)脾细胞和238个IL-4 SFU/10e(6)脾细胞。用Gag CD4肽刺激后，来自免疫小鼠的脾细胞也产生了高水平的Th1和Th2细胞因子。IFN-γ、TNF-α、IL-4和IL-5的水平分别比背景高7.5倍、29.1倍、26.2倍和89.3倍。在免疫小鼠的血清中检测到了HIV-1 Gag特异性IgG1和IgG2a抗体。
该研究突出了经口递送的减毒沙门氏菌作为HIV-1 C亚型Gag的黏膜疫苗载体的潜力，可诱导Gag特异性CD4+ Th1和Th2细胞免疫应答以及抗体，而这些可能是预防HIV-1感染所需的重要特性。
