van der Lubbe Joan E M, Rosendahl Huber Sietske K, Vijayan Aneesh, Dekking Liesbeth, van Huizen Ella, Vreugdenhil Jessica, Choi Ying, Baert Miranda R M, Feddes-de Boer Karin, Izquierdo Gil Ana, van Heerden Marjolein, Dalebout Tim J, Myeni Sebenzile K, Kikkert Marjolein, Snijder Eric J, de Waal Leon, Stittelaar Koert J, Tolboom Jeroen T B M, Serroyen Jan, Muchene Leacky, van der Fits Leslie, Rutten Lucy, Langedijk Johannes P M, Barouch Dan H, Schuitemaker Hanneke, Zahn Roland C, Wegmann Frank
Janssen Vaccines & Prevention B.V., Leiden, The Netherlands.
Janssen Non-Clinical Safety B.V., Beerse, Belgium.
NPJ Vaccines. 2021 Mar 19;6(1):39. doi: 10.1038/s41541-021-00301-y.
Previously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy, and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1 × 10 and 1 × 10 VP elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers that was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these preclinical data confirm efficacy of a one-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.
此前我们已经表明，单剂量表达预融合稳定化严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突抗原的重组腺病毒血清型26（Ad26）疫苗（Ad26.COV2.S）具有免疫原性，并在叙利亚仓鼠和非人类灵长类动物SARS-CoV-2感染模型中提供保护。在此，我们在中度疾病叙利亚仓鼠攻毒模型中，使用当前最流行的G614刺突SARS-CoV-2变体，研究了Ad26.COV2.S介导的免疫原性、保护效力以及疫苗相关增强呼吸道疾病（VAERD）的可能性。1×10⁸和1×10⁹病毒粒子剂量的疫苗引发了大量中和抗体滴度，并完全保护超过80%接种SARS-CoV-2的叙利亚仓鼠免受肺部感染和肺炎，但不能预防上呼吸道感染。第二剂疫苗进一步提高了中和抗体滴度，这与SARS-CoV-2攻毒后上呼吸道中感染性病毒载量的降低相关。低剂量Ad26.COV2.S疫苗接种引发的次优非保护性免疫反应，并未加重SARS-CoV-2接种的叙利亚仓鼠突破性感染后的呼吸道疾病。此外，降低疫苗剂量可以确定结合和中和抗体滴度与下呼吸道保护概率相关。总体而言，这些临床前数据证实了单剂量Ad26.COV2.S疫苗方案在该G614刺突SARS-CoV-2病毒变体叙利亚仓鼠模型中的有效性，显示了第二剂疫苗的额外益处，并证明在次优免疫条件下没有VAERD的迹象。
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