Aghasadeghi Mohammad Reza, Salmani Ali Sharifat, Sadat Seyed Mehdi, Javadi Foozieh, Memarnejadian Arash, Vahabpour Rouhoullah, Zabihollahi Rezvan, Moshiri Arfa, Siadat Seyed Davar
Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
Curr HIV Res. 2011 Dec 1;9(8):630-5. doi: 10.2174/157016211798998772.
Despite the worldwide efforts made in the field of HIV vaccine development, an efficient AIDS vaccine strategy is still vague. Virus-like particles (VLPs) are one of the introduced aspects for HIV vaccine development since the non-replicative nature of HIV VLPs, resulting from the lack of viral genomic RNA, makes them suitable for broad applications. We have previously designed and introduced non-infectious VLPs (mzNL4-3) by introduction of a deletion mutation in the reverse transcriptase and integrase coding regions of HV-1. There are evidences suggesting that an effective cellular immune response against HIV-1 is able to control and suppress viremia during primary and chronic HIV infections. In the present study we have evaluated the potency of mzNL4-3 VLPs mixed with Neisseria meningitidis serogroup B outer-membrane vesicle (OMV), which is among the microbial components with proved adjuvant properties, to induce humoral and cellular responses against HIV-1. Analysis of anti-HIV-1 responses elicited in immunized BALB/c mice following different immunization regimens indicated OMV+VLP as an immunopotent combination which significantly induced anti-HIV-1 IgG with IgG2a dominancy. Results of cytokine and ELISpot assays also showed the capability of VLP+OMV immunogen for effective induction of IFN-gamma; and IL4 secreting cells and further suggested the promotion of Th1-oriented response that was evidenced with the increased IFN-γ/IL4 secretion ratio. According to our study, HIV-1 VLPs combined with N. meningitidis B OMVs seem to be a promising approach in vaccine development against HIV-1.
尽管全球在HIV疫苗研发领域付出了诸多努力,但高效的艾滋病疫苗策略仍不明确。病毒样颗粒(VLPs)是HIV疫苗研发引入的方面之一,因为HIV VLPs缺乏病毒基因组RNA,具有非复制性,使其适合广泛应用。我们之前通过在HV-1逆转录酶和整合酶编码区引入缺失突变,设计并引入了非感染性VLPs(mzNL4-3)。有证据表明,针对HIV-1的有效细胞免疫反应能够在原发性和慢性HIV感染期间控制和抑制病毒血症。在本研究中,我们评估了与具有佐剂特性的微生物成分之一的B群脑膜炎奈瑟菌外膜囊泡(OMV)混合的mzNL4-3 VLPs诱导针对HIV-1的体液和细胞反应的效力。对不同免疫方案免疫的BALB/c小鼠中引发的抗HIV-1反应的分析表明,OMV+VLP是一种免疫强效组合,可显著诱导以IgG2a为主的抗HIV-1 IgG。细胞因子和ELISpot检测结果还显示VLP+OMV免疫原能够有效诱导IFN-γ分泌细胞和IL4分泌细胞,并进一步表明促进了以Th1为主的反应,这在IFN-γ/IL4分泌比值增加中得到了证实。根据我们的研究,HIV-1 VLPs与B群脑膜炎奈瑟菌OMV联合似乎是一种有前景的HIV-1疫苗研发方法。