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T细胞诱导型疫苗可降低中和抗体效能阈值
2020-05-13 12:19
来源：小柯机器人

美国斯坦福大学Bali Pulendran、埃默里大学Rama R. Amara、Eric Hunter、Cynthia A. Derdeyn、明尼苏达大学David Masopust等研究人员合作发现，即使在中和抗体效价较低的情况下，T细胞诱导型疫苗也能持久预防粘膜SHIV感染。2020年5月11日，《自然—医学》在线发表了这一成果。

最近HIV疫苗方面的工作集中于诱导广泛的中和抗体，但同时引起中和抗体（nAb）和细胞应答可能更好。研究人员使用了HIV包膜三聚体来免疫猕猴，可单独诱导中和抗体（nAb），或者与异源病毒载体一起诱导nAb和细胞免疫，包括CD8+组织驻留性记忆T细胞。在用自体病毒对阴道进行十次感染后，两个疫苗组的保护率分别为53.3％和66.7％。nAb效价大于300通常与保护作用有关，但在异源病毒载体加nAb组中，效价小于300也足够。
 
在该组中，保护是持久的，因为动物在5个月后又抵抗了六次感染。离体阴道组织培养物中T细胞的抗原刺激触发了髓样和CD4+T细胞中的抗病毒反应。研究人员认为，细胞免疫反应可以降低实现高效和持久保护所需的nAb阈值。
 
附：英文原文
 
Title: T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers

Author: Prabhu S. Arunachalam, Tysheena P. Charles, Vineet Joag, Venkata S. Bollimpelli, Madeleine K. D. Scott, Florian Wimmers, Samantha L. Burton, Celia C. Labranche, Caroline Petitdemange, Sailaja Gangadhara, Tiffany M. Styles, Clare F. Quarnstrom, Korey A. Walter, Thomas J. Ketas, Traci Legere, Pradeep Babu Jagadeesh Reddy, Sudhir Pai Kasturi, Anthony Tsai, Bertrand Z. Yeung, Shakti Gupta, Mark Tomai, John Vasilakos, George M. Shaw, Chil-Yong Kang, John P. Moore, Shankar Subramaniam, Purvesh Khatri, David Montefiori, Pamela A. Kozlowski, Cynthia A. Derdeyn, Eric Hunter, David Masopust, Rama R. Amara, Bali Pulendran

Issue&Volume: 2020-05-11

Abstract: Recent efforts toward an HIV vaccine focus on inducing broadly neutralizing antibodies, but eliciting both neutralizing antibodies (nAbs) and cellular responses may be superior. Here, we immunized macaques with an HIV envelope trimer, either alone to induce nAbs, or together with a heterologous viral vector regimen to elicit nAbs and cellular immunity, including CD8+ tissue-resident memory T cells. After ten vaginal challenges with autologous virus, protection was observed in both vaccine groups at 53.3% and 66.7%, respectively. A nAb titer >300 was generally associated with protection but in the heterologous viral vector+nAb group, titers <300 were sufficient. In this group, protection was durable as the animals resisted six more challenges 5 months later. Antigen stimulation of T cells in ex vivo vaginal tissue cultures triggered antiviral responses in myeloid and CD4+ T cells. We propose that cellular immune responses reduce the threshold of nAbs required to confer superior and durable protection.

DOI: 10.1038/s41591-020-0858-8

Source: https://www.nature.com/articles/s41591-020-0858-8

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


本期文章：《自然—医学》：Online/在线发表

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