Vaxine Pty Ltd., Bedford Park, Adelaide, SA 5042, Australia; College of Medicine and Public Health, Flinders University, Adelaide, SA 5042, Australia.
Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Vaccine. 2023 Nov 22;41(48):7116-7128. doi: 10.1016/j.vaccine.2023.10.018. Epub 2023 Oct 19.
The ongoing evolution of SARS-CoV-2 variants emphasizes the need for vaccines providing broad cross-protective immunity. This study was undertaken to assess the ability of Advax-CpG55.2 adjuvanted monovalent recombinant spike protein (Wuhan, Beta, Gamma) vaccines or a trivalent formulation to protect hamsters againstBeta or Delta virus infection. The ability of vaccines to block virus transmission to naïve co-housed animals was also assessed. In naïve hosts, the Beta variant induced higher virus loads than the Delta variant, and conversely the Delta variant caused more severe disease and was more likely to be associated with virus transmission. The trivalent vaccine formulation provided the best protection against both Beta and Delta infection and also completely prevented virus transmission. The next best performing vaccine was the original monovalent Wuhan-based vaccine. Notably, hamsters that received the monovalent Gamma spike vaccine had the highest viral loads and clinical disease of all the vaccine groups, a potential signal of antibody dependent-enhancement (ADE). These hamsters were also the most likely to transmit Delta virus to naïve recipients. In murine studies, the Gamma spike vaccine induced the highest total spike protein to RBD IgG ratio and the lowest levels of neutralizing antibody, a context that could predispose to ADE. Overall, the study results confirmed that the current SpikoGen® vaccine based on Wuhan spike protein was still able to protect against clinical disease caused by either the Beta or Delta virus variants but suggested additional protection may be obtained by combining it with extra variant spike proteins to make a multivalent formulation. This study highlights the complexity of optimizing vaccine protection against multiple SARS-CoV-2 variants and stresses the need to continue to pursue new and improved COVID-19 vaccines able to provide robust, long-lasting, and broadly cross-protective immunity against constantly evolving SARS-CoV-2 variants.
不断演变的 SARS-CoV-2 变体强调了需要提供广泛的交叉保护免疫的疫苗。本研究旨在评估 Advax-CpG55.2 佐剂单价重组刺突蛋白（武汉、贝塔、伽马）疫苗或三价配方对保护仓鼠免受 Beta 或 Delta 病毒感染的能力。还评估了疫苗阻止病毒传播给未感染的同居动物的能力。在未感染的宿主中，Beta 变体引起的病毒载量高于 Delta 变体，反之亦然，Delta 变体导致更严重的疾病，并且更有可能与病毒传播相关。三价疫苗配方对 Beta 和 Delta 感染提供了最佳保护，并且完全阻止了病毒传播。表现第二好的疫苗是最初的单价基于武汉的疫苗。值得注意的是，接受单价 Gamma 刺突疫苗的仓鼠具有所有疫苗组中最高的病毒载量和临床疾病，这是抗体依赖性增强（ADE）的潜在信号。这些仓鼠也是最有可能将 Delta 病毒传播给未感染的受者的仓鼠。在鼠类研究中，Gamma 刺突疫苗诱导的总刺突蛋白与 RBD IgG 比值最高，中和抗体水平最低，这种情况可能导致 ADE。总体而言，研究结果证实，基于武汉刺突蛋白的当前 SpikoGen®疫苗仍能预防由 Beta 或 Delta 病毒变体引起的临床疾病，但建议通过与额外的变体刺突蛋白结合来获得额外的保护，以制成多价配方。本研究强调了优化针对多种 SARS-CoV-2 变体的疫苗保护的复杂性，并强调需要继续寻求新的和改进的 COVID-19 疫苗，以提供针对不断演变的 SARS-CoV-2 变体的强大、持久和广泛的交叉保护免疫。
