小柯机器人

美国国家卫生研究院Paolo Lusso小组发现，一种env-gag VLP mRNA疫苗可降低猕猴中异源SHIV感染的风险 。2021年12月9日，国际知名学术期刊《自然—医学》在线发表了这一成果。

研究人员发现，一种信使RNA（mRNA）疫苗共同表达膜锚定的HIV-1包膜（Env）和猿免疫缺陷病毒（SIV）Gag蛋白来产生病毒样颗粒（VLP），能诱导出能够广泛中和的抗体并降低猕猴的感染风险。在小鼠中，用共同配制的env和gag mRNA进行免疫，在诱导中和抗体方面优于单独的env mRNA。猕猴用缺乏N276糖基的传递型B族env mRNA进行初选，然后用糖基修复的自体和随后的双价异源env（A族和C族）进行多次加强免疫。

这种方案具有高度的免疫原性，并能引起针对最流行的（二级）HIV-1病毒株的中和抗体，同时伴有强大的抗Env CD4⁺ T细胞反应。接种疫苗的动物在反复接受异源2级模拟人免疫缺陷病毒（SHIV AD8）的低剂量粘膜感染时，每次暴露风险降低了79%。因此，多级env-gag VLP mRNA平台是开发HIV-1疫苗的一种潜在方法。

据悉，开发一种保护性疫苗仍然是控制艾滋病毒/艾滋病流行的首要任务。

附：英文原文

Title: A multiclade env–gag VLP mRNA vaccine elicits tier-2 HIV-1-neutralizing antibodies and reduces the risk of heterologous SHIV infection in macaques

Author: Zhang, Peng, Narayanan, Elisabeth, Liu, Qingbo, Tsybovsky, Yaroslav, Boswell, Kristin, Ding, Shilei, Hu, Zonghui, Follmann, Dean, Lin, Yin, Miao, Huiyi, Schmeisser, Hana, Rogers, Denise, Falcone, Samantha, Elbashir, Sayda M., Presnyak, Vladimir, Bahl, Kapil, Prabhakaran, Madhu, Chen, Xuejun, Sarfo, Edward K., Ambrozak, David R., Gautam, Rajeev, Martin, Malcom A., Swerczek, Joanna, Herbert, Richard, Weiss, Deborah, Misamore, Johnathan, Ciaramella, Giuseppe, Himansu, Sunny, Stewart-Jones, Guillaume, McDermott, Adrian, Koup, Richard A., Mascola, John R., Finzi, Andrs, Carfi, Andrea, Fauci, Anthony S., Lusso, Paolo

Issue&Volume: 2021-12-09

Abstract: The development of a protective vaccine remains a top priority for the control of the HIV/AIDS pandemic. Here, we show that a messenger RNA (mRNA) vaccine co-expressing membrane-anchored HIV-1 envelope (Env) and simian immunodeficiency virus (SIV) Gag proteins to generate virus-like particles (VLPs) induces antibodies capable of broad neutralization and reduces the risk of infection in rhesus macaques. In mice, immunization with co-formulated env and gag mRNAs was superior to env mRNA alone in inducing neutralizing antibodies. Macaques were primed with a transmitted-founder clade-B env mRNA lacking the N276 glycan, followed by multiple booster immunizations with glycan-repaired autologous and subsequently bivalent heterologous envs (clades A and C). This regimen was highly immunogenic and elicited neutralizing antibodies against the most prevalent (tier-2) HIV-1 strains accompanied by robust anti-Env CD4+ Tcell responses. Vaccinated animals had a 79% per-exposure risk reduction upon repeated low-dose mucosal challenges with heterologous tier-2 simian–human immunodeficiency virus (SHIVAD8). Thus, the multiclade env–gag VLP mRNA platform represents a promising approach for the development of an HIV-1 vaccine.

DOI: 10.1038/s41591-021-01574-5

Source: https://www.nature.com/articles/s41591-021-01574-5

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex