S Arunachalam Prabhu, Walls Alexandra C, Golden Nadia, Atyeo Caroline, Fischinger Stephanie, Li Chunfeng, Aye Pyone, Navarro Mary Jane, Lai Lilin, Edara Venkata Viswanadh, Roltgen Katharina, Rogers Kenneth, Shirreff Lisa, Ferrell Douglas E, Wrenn Samuel, Pettie Deleah, Kraft John C, Miranda Marcos C, Kepl Elizabeth, Sydeman Claire, Brunette Natalie, Murphy Michael, Fiala Brooke, Carter Lauren, White Alexander G, Trisal Meera, Hsieh Ching-Lin, Russell-Lodrigue Kasi, Monjure Christopher, Dufour Jason, Doyle-Meyer Lara, Bohm Rudolph B, Maness Nicholas J, Roy Chad, Plante Jessica A, Plante Kenneth S, Zhu Alex, Gorman Matthew J, Shin Sally, Shen Xiaoying, Fontenot Jane, Gupta Shakti, O Hagan Derek T, Most Robbert Van Der, Rappuoli Rino, Coffman Robert L, Novack David, McLellan Jason S, Subramaniam Shankar, Montefiori David, Boyd Scott D, Flynn JoAnne L, Alter Galit, Villinger Francois, Kleanthous Harry, Rappaport Jay, Suthar Mehul, King Neil P, Veesler David, Pulendran Bali
bioRxiv. 2021 Feb 11:2021.02.10.430696. doi: 10.1101/2021.02.10.430696.
The development of a portfolio of SARS-CoV-2 vaccines to vaccinate the global population remains an urgent public health imperative. Here, we demonstrate the capacity of a subunit vaccine under clinical development, comprising the SARS-CoV-2 Spike protein receptor-binding domain displayed on a two-component protein nanoparticle (RBD-NP), to stimulate robust and durable neutralizing antibody (nAb) responses and protection against SARS-CoV-2 in non-human primates. We evaluated five different adjuvants combined with RBD-NP including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an alpha-tocopherol-containing squalene-based oil-in-water emulsion used in pandemic influenza vaccines; AS37, a TLR-7 agonist adsorbed to Alum; CpG 1018-Alum (CpG-Alum), a TLR-9 agonist formulated in Alum; or Alum, the most widely used adjuvant. All five adjuvants induced substantial nAb and CD4 T cell responses after two consecutive immunizations. Durable nAb responses were evaluated for RBD-NP/AS03 immunization and the live-virus nAb response was durably maintained up to 154 days post-vaccination. AS03, CpG-Alum, AS37 and Alum groups conferred significant protection against SARS-CoV-2 infection in the pharynges, nares and in the bronchoalveolar lavage. The nAb titers were highly correlated with protection against infection. Furthermore, RBD-NP when used in conjunction with AS03 was as potent as the prefusion stabilized Spike immunogen, HexaPro. Taken together, these data highlight the efficacy of the RBD-NP formulated with clinically relevant adjuvants in promoting robust immunity against SARS-CoV-2 in non-human primates.
开发一系列严重急性呼吸综合征冠状病毒2（SARS-CoV-2）疫苗以接种全球人口仍然是一项紧迫的公共卫生要务。在此，我们展示了一种正在临床开发的亚单位疫苗的能力，该疫苗由展示在双组分蛋白质纳米颗粒（RBD-NP）上的SARS-CoV-2刺突蛋白受体结合域组成，能够在非人类灵长类动物中刺激产生强大且持久的中和抗体（nAb）反应以及针对SARS-CoV-2的保护作用。我们评估了与RBD-NP联合使用的五种不同佐剂，包括水包油乳剂Essai O/W 1849101；AS03，一种用于大流行性流感疫苗的含α-生育酚的角鲨烯基水包油乳剂；AS37，一种吸附于明矾的Toll样受体7（TLR-7）激动剂；CpG 1018-明矾（CpG-明矾），一种在明矾中配制的TLR-9激动剂；或明矾，最广泛使用的佐剂。所有五种佐剂在连续两次免疫后均诱导出大量的nAb和CD4 T细胞反应。对RBD-NP/AS03免疫的持久nAb反应进行了评估，接种疫苗后长达154天，活病毒nAb反应持续维持。AS03、CpG-明矾、AS37和明矾组在咽部、鼻腔以及支气管肺泡灌洗中对SARS-CoV-2感染提供了显著保护。nAb滴度与抗感染保护高度相关。此外，RBD-NP与AS03联合使用时与预融合稳定化刺突免疫原HexaPro一样有效。综上所述，这些数据突出了用临床相关佐剂配制的RBD-NP在促进非人类灵长类动物对SARS-CoV-2产生强大免疫力方面的功效。
