Vaxine Pty Ltd., 11 Walkley Avenue, Warradale, SA 5046, Australia; Flinders University, Bedford Park, SA 5042, Australia.
Vaxine Pty Ltd., 11 Walkley Avenue, Warradale, SA 5046, Australia.
Vaccine. 2023 Jul 19;41(32):4710-4718. doi: 10.1016/j.vaccine.2023.06.063. Epub 2023 Jun 19.
Traditional protein-based vaccine approaches to COVID-19 were overshadowed by the new mRNA and adenoviral vector vaccine approaches which were first to receive marketing authorization. The current study tested for the first time in repurposed aged (median 15.4 years) cynomolgus macaques, a novel Advax-CpG55.2™ adjuvanted recombinant extracellular domain spike protein trimer antigen for immunogenicity, protection and safety. Nine animals received two intramuscular injections 10 days apart of recombinant spike protein (25 μg) with Advax-CpG55.2™ (10 mg/200 μg) and 5 controls received saline injections. Serum antibody levels were followed for 3 months and then the animals were challenged with SARS-CoV-2 virus. Clinical signs, local reactions, body weight, food consumption and antibody levels were monitored till termination on either day 3 or 7 post-infection. Two weeks after the second dose, 8/9 immunized macaques had high serum spike and receptor binding domain binding antibodies that were able to cross-neutralize Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and, to a lesser extent, Omicron variants (B.1.1.529 ). Antibody levels decayed over the subsequent 3 months, and minimal neutralizing antibody was detectable immediately prior to the challenge which used a vaccine-homologous Wuhan-like ancestral virus. Of the nine vaccinated animals, only one 18-year-old female sacrificed at d3 had low levels of lung virus, versus 100 % of the control animals. Four of 5 (80 %) control animals had positive lung staining for SARS-CoV-2 virus versus just 1 of 9 (11 %) in the immunized group. The immunized animals exhibited better maintenance of appetite post-challenge. Neutralizing antibody levels rebounded rapidly in immunized animals, post-challenge. This data supports the benefits of Advax-CpG adjuvanted recombinant spike protein vaccine in protecting against a homologous SARS-CoV-2 infection.
传统的基于蛋白质的 COVID-19 疫苗方法被新的 mRNA 和腺病毒载体疫苗方法所掩盖，后者首先获得了市场授权。本研究首次在重新使用的老年（中位数 15.4 岁）食蟹猴中测试了新型 Advax-CpG55.2™佐剂的重组细胞外域刺突蛋白三聚体抗原的免疫原性、保护和安全性。9 只动物接受了两次肌肉内注射，间隔 10 天，分别为重组刺突蛋白（25μg）与 Advax-CpG55.2™（10mg/200μg），5 只对照动物接受生理盐水注射。监测血清抗体水平 3 个月，然后用 SARS-CoV-2 病毒对动物进行攻毒。监测临床症状、局部反应、体重、食物消耗和抗体水平，直到感染后第 3 或 7 天终止。第二次给药后 2 周，8/9 只免疫猴的血清刺突和受体结合域结合抗体水平较高，能够交叉中和 Alpha（B.1.1.7）、Beta（B.1.351）、Gamma（P.1）、Delta（B.1.617.2），以及在较小程度上，Omicron 变体（B.1.1.529）。抗体水平在随后的 3 个月内下降，在使用与疫苗同源的武汉样祖先病毒进行攻毒前，可检测到最低水平的中和抗体。在 9 只接种疫苗的动物中，只有一只 18 岁的雌性动物（d3 时）肺部病毒载量较低，而对照组 100%的动物肺部病毒载量均较高。5 只对照组中的 4 只（80%）对 SARS-CoV-2 病毒呈阳性肺染色，而免疫组中只有 9 只中的 1 只（11%）呈阳性肺染色。免疫动物在攻毒后表现出更好的食欲维持。免疫动物的中和抗体水平在攻毒后迅速反弹。这些数据支持 Advax-CpG 佐剂的重组刺突蛋白疫苗在预防同源 SARS-CoV-2 感染方面的益处。
