Comparative immunogenicity of HIV-1 gp160, gp140 and gp120 expressed by live attenuated newcastle disease virus vector.
Comparative immunogenicity of HIV-1 gp160, gp140 and gp120 expressed by live attenuated newcastle disease virus vector.
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DOI：
10.1371/journal.pone.0078521
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Samal SK
中科院分区：
文献类型：
--
作者：
Khattar SK;Samal S;LaBranche CC;Montefiori DC;Collins PL;Samal SK
开发一种能够在全身和粘膜水平诱导广泛的体液和细胞反应的人类免疫缺陷病毒-1 （HIV-1）疫苗对于防治全球艾滋病流行至关重要。我们之前证明了新城疫病毒（NDV）作为疫苗载体表达寡聚Env蛋白gp160并诱导有效的体液和粘膜免疫反应的能力。在本研究中，我们以NDV疫苗株LaSota为载体，比较了载体表达gp160、gp120和gp140 （gp160通过删除跨膜和细胞质结构域制成的衍生物）的生化和免疫原性特性，即gp140L包含完整的膜近端外区（MPER）， gp140S缺乏MPER的远端一半。我们发现，与gp160类似，ndv表达的gp140S和gp120，而不是gp140L，形成了高阶低聚物，保留了构象敏感的单克隆抗体的识别。与其他重组体相比，rLaSota/gp140S经鼻内途径免疫豚鼠可产生更大的全身和粘膜抗体反应。与rLaSota/160诱导的Th1偏倚免疫应答相比，rLaSota/140S、rLaSota/140L和rLaSota/120免疫产生混合的Th1/Th2免疫应答。重要的是，rLaSota/gp140S诱导了对同源HIV-1株BaL的中和抗体反应。26和实验室适应的HIV-1毒株MN.3比其他NDV重组引发的毒株更强。此外，rLaSota/gp140S在小鼠中诱导更大的CD4+和CD8+ t细胞反应。这些研究表明，rLaSota/gp140S是一种很有希望的候选疫苗，可以引发对HIV-1 Env蛋白的有效粘膜、体液和细胞免疫反应。
The development of a vaccine against human immunodeficiency virus-1 (HIV-1) capable of inducing broad humoral and cellular responses at both the systemic and mucosal levels will be critical for combating the global AIDS epidemic. We previously demonstrated the ability of Newcastle disease virus (NDV) as a vaccine vector to express oligomeric Env protein gp160 and induce potent humoral and mucosal immune responses. In the present study, we used NDV vaccine strain LaSota as a vector to compare the biochemical and immunogenic properties of vector-expressed gp160, gp120, and two versions of gp140 (a derivative of gp160 made by deleting the transmembrane and cytoplasmic domains), namely: gp140L, which contained the complete membrane-proximal external region (MPER), and gp140S, which lacks the distal half of MPER. We show that, similar to gp160, NDV-expressed gp140S and gp120, but not gp140L, formed higher-order oligomers that retained recognition by conformationally sensitive monoclonal antibodies. Immunization of guinea pigs by the intranasal route with rLaSota/gp140S resulted in significantly greater systemic and mucosal antibody responses compared to the other recombinants. Immunization with rLaSota/140S, rLaSota/140L rLaSota/120 resulted in mixed Th1/Th2 immune responses as compared to Th1-biased immune responses induced by rLaSota/160. Importantly, rLaSota/gp140S induced neutralizing antibody responses to homologous HIV-1 strain BaL.26 and laboratory adapted HIV-1 strain MN.3 that were stronger than those elicited by the other NDV recombinants. Additionally, rLaSota/gp140S induced greater CD4+ and CD8+ T-cell responses in mice. These studies illustrate that rLaSota/gp140S is a promising vaccine candidate to elicit potent mucosal, humoral and cellular immune responses to the HIV-1 Env protein.
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影响因子：
64.8
作者：
Huang J;Ofek G;Laub L;Louder MK;Doria-Rose NA;Longo NS;Imamichi H;Bailer RT;Chakrabarti B;Sharma SK;Alam SM;Wang T;Yang Y;Zhang B;Migueles SA;Wyatt R;Haynes BF;Kwong PD;Mascola JR;Connors M
通讯作者：
Connors M
影响因子：
56.9
作者：
Haynes, BF;Fleming, J;Alam, SM
通讯作者：
Alam, SM
影响因子：
5.4
作者：
Carnero, Elena;Li, Wenjing;Garcia-Sastre, Adolfo
通讯作者：
Garcia-Sastre, Adolfo
影响因子：
6.4
作者：
Graham, BS;McElrath, MJ;Fast, PE
通讯作者：
Fast, PE
影响因子：
5.4
作者：
DiNapoli, Joshua M.;Nayak, Baibaswata;Bukreyev, Alexander
通讯作者：
Bukreyev, Alexander