Chimeric Human Papillomavirus-16 Virus-like Particles Presenting P18I10 and T20 Peptides from HIV-1 Envelope Induce HPV16 and HIV-1-Specific Humoral and T Cell-Mediated Immunity in BALB/c Mice.

Chimeric Human Papillomavirus-16 Virus-like Particles Presenting P18I10 and T20 Peptides from HIV-1 Envelope Induce HPV16 and HIV-1-Specific Humoral and T Cell-Mediated Immunity in BALB/c Mice.
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DOI:
10.3390/vaccines11010015
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发表时间:
2022-12-21
期刊:
影响因子:
7.8
通讯作者:
Joseph-Munné J
Joseph-Munné J
中科院分区:
医学3区
文献类型:
--
作者:
Chen CW;Saubi N;Kilpeläinen A;Joseph-Munné J

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本研究利用哺乳动物细胞表达系统,将HIV-1 gp120 V3环衍生的HIV-1 P18I10 CTL肽和HIV-1 gp41的T20抗融合肽插入HPV16 L1衣壳蛋白中,构建嵌合HPV:HIV (L1:P18I10和L1:T20) VLPs。用层析法纯化HPV:HIV VLPs。我们证明将P18I10或T20肽插入hpv16l1衣壳蛋白的DE环中不会影响嵌合HPV:HIV VLPs的体外稳定性、自组装和形态。重要的是,它既不会干扰嵌合HPV:HIV VLPs上的靶向序列和构象P18I10和T20肽的HIV-1抗体的反应性,也不会干扰体内hpv16l1特异性抗体的诱导。我们观察到嵌合L1:P18I10/L1:T20 VLPs疫苗可以诱导HPV16-但弱的hiv -1特异性抗体反应,并在BALB/c小鼠中诱导HPV16-和hiv -1特异性t细胞反应。此外,在rBCG启动后,可能是一种潜在的增强剂,以增加hiv特异性细胞应答。HIVA疫苗。本研究工作将有助于开发新型嵌合HPV:HIV vlp疫苗平台,以控制HPV16和HIV-1感染,这是发展中国家和工业化国家迫切需要的。
In this study, the HIV-1 P18I10 CTL peptide derived from the V3 loop of HIV-1 gp120 and the T20 anti-fusion peptide of HIV-1 gp41 were inserted into the HPV16 L1 capsid protein to construct chimeric HPV:HIV (L1:P18I10 and L1:T20) VLPs by using the mammalian cell expression system. The HPV:HIV VLPs were purified by chromatography. We demonstrated that the insertion of P18I10 or T20 peptides into the DE loop of HPV16 L1 capsid proteins did not affect in vitro stability, self-assembly and morphology of chimeric HPV:HIV VLPs. Importantly, it did not interfere either with the HIV-1 antibody reactivity targeting sequential and conformational P18I10 and T20 peptides presented on chimeric HPV:HIV VLPs or with the induction of HPV16 L1-specific antibodies in vivo. We observed that chimeric L1:P18I10/L1:T20 VLPs vaccines could induce HPV16- but weak HIV-1-specific antibody responses and elicited HPV16- and HIV-1-specific T-cell responses in BALB/c mice. Moreover, could be a potential booster to increase HIV-specific cellular responses in the heterologous immunization after priming with rBCG.HIVA vaccine. This research work would contribute a step towards the development of the novel chimeric HPV:HIV VLP-based vaccine platform for controlling HPV16 and HIV-1 infection, which is urgently needed in developing and industrialized countries.
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