Vaxine Pty Ltd., Bedford Park, Adelaide, SA 5042, Australia; Flinders University, Bedford Park, Adelaide, SA 5042, Australia.
Vaxine Pty Ltd., Bedford Park, Adelaide, SA 5042, Australia.
Vaccine. 2023 Sep 22;41(41):6093-6104. doi: 10.1016/j.vaccine.2023.08.053. Epub 2023 Aug 31.
SpikoGen® is a recombinant spike protein vaccine against COVID-19 that obtained marketing authorization in the Middle East on October 6, 2021, becoming the first adjuvanted protein-based COVID-19 vaccine of its type to achieve approval. SpikoGen® vaccine utilizes a unique adjuvant Advax-CpG55.2, which comprises delta inulin and CpG55.2 oligonucleotide, a synthetic human toll-like receptor (TLR)-9 agonist. As part of a safety assessment, developmental and reproductive toxicity (DART) studies were undertaken in mice of Advax-CpG55.2 adjuvanted formulations including SpikoGen®, a H7 hemagglutinin influenza vaccine (rH7HA), the bivalent combination of SpikoGen® and rH7HA, and a next-generation quadrivalent spike protein vaccine. In the first study, vaccines were administered intramuscularly to pregnant dams on gestation days (GD) 6.5 and 12.5, and in the second two doses were given in the pre-mating period with a further two doses during gestation. The doses used in the pregnant mice were 250-1000 times the usual human doses on a weight for weight basis. Strong serum antibody responses with neutralizing activity against the relevant virus were seen in the immunized dams and also at the time of weaning in the sera of their pups, consistent with robust maternal antibody transfer. No adverse effects of any of the vaccine formulations were observed in the immunized dams or their pups. Notably, there were no adverse effects of any of the Advax-CpG55.2 adjuvanted vaccines on female mating performance, fertility, ovarian or uterine parameters, embryo-fetal or postnatal survival, fetal growth, or neurofunctional development. No evidence of antigen interference was observed when SpikoGen® vaccine was mixed and co-administered with influenza hemagglutinin vaccine to pregnant dams. Together with the strong safety profile of SpikoGen® vaccine seen in adults and children in human trials, this DART study data supports the safety of Advax-CpG55.2 adjuvanted COVID-19 and influenza vaccine in women of childbearing potential including during pregnancy.
SpikoGen® 是一种针对 COVID-19 的重组刺突蛋白疫苗，于 2021 年 10 月 6 日在中东获得上市许可，成为首个获得批准的同类佐剂蛋白 COVID-19 疫苗。SpikoGen® 疫苗利用了独特的佐剂 Advax-CpG55.2，其包含了 delta 菊粉和 CpG55.2 寡核苷酸，一种合成的人类 Toll 样受体（TLR）-9 激动剂。作为安全性评估的一部分，在包括 SpikoGen®疫苗、H7 血凝素流感疫苗（rH7HA）、SpikoGen®和 rH7HA 双价组合以及下一代四价刺突蛋白疫苗在内的 Advax-CpG55.2 佐剂制剂的小鼠中进行了发育和生殖毒性（DART）研究。在第一项研究中，疫苗于妊娠第 6.5 和 12.5 天经肌肉注射给怀孕的母鼠，在第二项中，在交配前给予两剂，在妊娠期间再给予两剂。在怀孕的小鼠中使用的剂量是基于体重的常规人类剂量的 250-1000 倍。免疫的母鼠及其幼鼠的血清中均产生了针对相关病毒的强烈血清抗体反应和中和活性，这与强大的母体抗体转移一致。在免疫的母鼠或其幼鼠中未观察到任何疫苗制剂的不良反应。值得注意的是，Advax-CpG55.2 佐剂疫苗对雌性交配性能、生育能力、卵巢或子宫参数、胚胎-胎儿或产后存活率、胎儿生长或神经功能发育均无不良影响。当 SpikoGen®疫苗与流感血凝素疫苗混合并同时给予怀孕的母鼠时，未观察到抗原干扰的证据。结合 SpikoGen®疫苗在成人和儿童临床试验中的强烈安全性概况，这项 DART 研究数据支持 Advax-CpG55.2 佐剂 COVID-19 和流感疫苗在有生育潜力的女性中（包括怀孕期间）的安全性。
