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Abstract：
An effective human immunodeficiency virus type 1 (HIV-1) vaccine must induce protective antibody responses, as well as CD4(+) and CD8(+) T cell responses, that can be effective despite extraordinary diversity of HIV-1. The consensus and mosaic immunogens are complete but artificial proteins, computationally designed to elicit immune responses with improved cross-reactive breadth, to attempt to overcome the challenge of global HIV diversity. In this study, we have compared the immunogenicity of a transmitted-founder (T/F) B clade Env (B.1059), a global group M consensus Env (Con-S), and a global trivalent mosaic Env protein in rhesus macaques. These antigens were delivered using a DNA prime-recombinant NYVAC (rNYVAC) vector and Env protein boost vaccination strategy. While Con-S Env was a single sequence, mosaic immunogens were a set of three Envs optimized to include the most common forms of potential T cell epitopes. Both Con-S and mosaic sequences retained common amino acids encompassed by both antibody and T cell epitopes and were central to globally circulating strains. Mosaics and Con-S Envs expressed as full-length proteins bound well to a number of neutralizing antibodies with discontinuous epitopes. Also, both consensus and mosaic immunogens induced significantly higher gamma interferon (IFN-γ) enzyme-linked immunosorbent spot assay (ELISpot) responses than B.1059 immunogen. Immunization with these proteins, particularly Con-S, also induced significantly higher neutralizing antibodies to viruses than B.1059 Env, primarily to tier 1 viruses. Both Con-S and mosaics stimulated more potent CD8-T cell responses against heterologous Envs than did B.1059. Both antibody and cellular data from this study strengthen the concept of using in silico-designed centralized immunogens for global HIV-1 vaccine development strategies.
OBJECTIVE: There is an increasing appreciation for the importance of vaccine-induced anti-Env antibody responses for preventing HIV-1 acquisition. This nonhuman primate study demonstrates that in silico-designed global HIV-1 immunogens, designed for a human clinical trial, are capable of eliciting not only T lymphocyte responses but also potent anti-Env antibody responses.
OBJECTIVE: There is an increasing appreciation for the importance of vaccine-induced anti-Env antibody responses for preventing HIV-1 acquisition. This nonhuman primate study demonstrates that in silico-designed global HIV-1 immunogens, designed for a human clinical trial, are capable of eliciting not only T lymphocyte responses but also potent anti-Env antibody responses.
摘要：
有效的人类免疫缺陷病毒1型（HIV-1）疫苗必须诱导保护性抗体反应，以及CD4（+）和CD8（+）T细胞反应，尽管HIV-1具有非凡的多样性，但这仍然是有效的。共识和镶嵌免疫原是完整的，但人工蛋白，通过计算设计来引发具有改进的交叉反应宽度的免疫反应，试图克服全球艾滋病毒多样性的挑战。在这项研究中,我们比较了传播创始人（T/F）B进化枝Env（B.1059）的免疫原性，全球集团M共识Env(Con-S)，和恒河猴中的全局三价镶嵌Env蛋白。使用DNA引发重组NYVAC(rNYVAC)载体和Env蛋白加强疫苗接种策略递送这些抗原。虽然Con-SEnv是一个单一序列，镶嵌免疫原是一组三个Envs优化，包括最常见形式的潜在T细胞表位。Con-S和镶嵌序列都保留了抗体和T细胞表位所涵盖的共同氨基酸，并且对全球循环菌株至关重要。以全长蛋白表达的Mosaics和Con-SEnvs与许多具有不连续表位的中和抗体良好结合。此外，与B.1059免疫原相比，共有免疫原和镶嵌免疫原均诱导了显着更高的γ干扰素（IFN-γ）酶联免疫吸附斑点测定（ELISpot）反应。用这些蛋白质免疫，特别是Con-S,也诱导了明显高于B.1059Env的病毒中和抗体，主要是第1层病毒。与B.1059相比,Con-S和嵌合体刺激更有效的针对异源Envs的CD8-T细胞应答。来自这项研究的抗体和细胞数据都加强了将计算机设计的集中式免疫原用于全球HIV-1疫苗开发策略的概念。
目的：人们越来越认识到疫苗诱导的抗Env抗体反应对预防HIV-1感染的重要性。这项非人类灵长类动物研究表明，在硅设计的全球HIV-1免疫原，设计用于人体临床试验，不仅能够引起T淋巴细胞应答,而且能够引起有效的抗Env抗体应答。
目的：人们越来越认识到疫苗诱导的抗Env抗体反应对预防HIV-1感染的重要性。这项非人类灵长类动物研究表明，在硅设计的全球HIV-1免疫原，设计用于人体临床试验，不仅能够引起T淋巴细胞应答,而且能够引起有效的抗Env抗体应答。
