Neutralizing Antibody Responses following Long-Term Vaccination with HIV-1 Env gp140 in Guinea Pigs.
Neutralizing Antibody Responses following Long-Term Vaccination with HIV-1 Env gp140 in Guinea Pigs.
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DOI：
10.1128/jvi.00369-18
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发表时间：
2018-07-01
影响因子：
5.4
通讯作者：
Barouch DH
中科院分区：
文献类型：
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作者：
Bricault CA;Kovacs JM;Badamchi-Zadeh A;McKee K;Shields JL;Gunn BM;Neubauer GH;Ghantous F;Jennings J;Gillis L;Perry J;Nkolola JP;Alter G;Chen B;Stephenson KE;Doria-Rose N;Mascola JR;Seaman MS;Barouch DH
能够引发有效和广泛中和抗体（bNAb）的疫苗接种方案仍然是HIV-1疫苗领域未实现的目标。在这里，我们报告的免疫原性的纵向初免/加强免疫接种方案与一个面板的HIV-1包膜（Env）gp 140蛋白免疫原在豚鼠在一段时间内的200周。我们评估了包括单价进化枝C gp 140的疫苗方案，（C97 ZA 012 [C97]），由四个进化枝C gp 140组成的四价方案（C97 ZA 012、459 C、405 C和939 C [4C]），以及由进化枝A、B、C和镶嵌gp 140组成的四价方案（分别为92 UG 037、PV0.4、C97 ZA 012和Mosaic 3.1 [ABCM]）。我们发现，4C和ABCM初免/加强方案能够随着时间的推移引发更大幅度和广度的靶向可变环2（V2）的结合抗体应答，而不是仅单价C97方案。进行超过2年的纵向加强方案增加了某些1级NAb应答的幅度，但没有增加异源2级NAb应答的幅度或宽度。这些数据表明，需要额外的免疫原设计策略来诱导广泛的高滴度2级NAb应答。重要性激发有效的广泛中和抗体（bNAb）仍然是HIV-1疫苗领域难以实现的目标。在这项研究中，我们探讨了使用不同的免疫原的长期接种方案，以确定我们是否可以在豚鼠中引发bNAb。我们发现，超过2年的纵向增强增加了第1层NAb响应，但没有增加第2层NAb响应的幅度和广度。这些数据表明，额外的免疫原设计和疫苗接种策略对于诱导广泛的2级NAb应答是必要的。
A vaccination regimen capable of eliciting potent and broadly neutralizing antibodies (bNAbs) remains an unachieved goal of the HIV-1 vaccine field. Here, we report the immunogenicity of longitudinal prime/boost vaccination regimens with a panel of HIV-1 envelope (Env) gp140 protein immunogens over a period of 200 weeks in guinea pigs. We assessed vaccine regimens that included a monovalent clade C gp140 (C97ZA012 [C97]), a tetravalent regimen consisting of four clade C gp140s (C97ZA012, 459C, 405C, and 939C [4C]), and a tetravalent regimen consisting of clade A, B, C, and mosaic gp140s (92UG037, PVO.4, C97ZA012, and Mosaic 3.1, respectively [ABCM]). We found that the 4C and ABCM prime/boost regimens were capable of eliciting greater magnitude and breadth of binding antibody responses targeting variable loop 2 (V2) over time than the monovalent C97-only regimen. The longitudinal boosting regimen conducted over more than 2 years increased the magnitude of certain tier 1 NAb responses but did not increase the magnitude or breadth of heterologous tier 2 NAb responses. These data suggest that additional immunogen design strategies are needed to induce broad, high-titer tier 2 NAb responses. IMPORTANCE The elicitation of potent, broadly neutralizing antibodies (bNAbs) remains an elusive goal for the HIV-1 vaccine field. In this study, we explored the use of a long-term vaccination regimen with different immunogens to determine if we could elicit bNAbs in guinea pigs. We found that longitudinal boosting over more than 2 years increased tier 1 NAb responses but did not increase the magnitude and breadth of tier 2 NAb responses. These data suggest that additional immunogen designs and vaccination strategies will be necessary to induce broad tier 2 NAb responses.