Counoupas Claudio, Chan Elizabeth, Pino Paco, Armitano Joshua, Johansen Matt D, Smith Lachlan J, Ashley Caroline L, Estapé Eva, Troyon Jean, Alca Sibel, Miemczyk Stefan, Hansbro Nicole G, Scandurra Gabriella, Britton Warwick J, Courant Thomas, Dubois Patrice M, Collin Nicolas, Mohan V Krishna, Hansbro Philip M, Wurm Maria J, Wurm Florian M, Steain Megan, Triccas James A
Sydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia.
Centre for Infection and Immunity, Centenary Institute, The University of Sydney, Camperdown, NSW, Australia.
NPJ Vaccines. 2025 May 8;10(1):89. doi: 10.1038/s41541-025-01144-7.
Next-generation vaccines are essential to address the evolving nature of SARS-CoV-2 and to protect against emerging pandemic threats from other coronaviruses. These vaccines should elicit broad protection, provide long-lasting immunity and ensure equitable access for all populations. In this study, we developed a panel of chimeric, full-length spike antigens incorporating mutations from previous, circulating and predicted SARS-CoV-2 variants. The lead candidate (CoVEXS5) was produced through a high-yield production process in stable CHO cells achieving >95% purity, demonstrated long-term stability and elicited broadly cross-reactive neutralising antibodies when delivered to mice in a squalene emulsion adjuvant (Sepivac SWE™). In both mice and hamsters, CoVEXS5 immunisation reduced clinical disease signs, lung inflammation and organ viral titres after SARS-CoV-2 infection, including following challenge with the highly immunoevasive Omicron XBB.1.5 subvariant. In mice previously primed with a licenced mRNA vaccine (Comirnaty XBB.1.5, termed mRNA-XBB), CoVEXS5 boosting significantly increased neutralising antibody (nAb) levels against viruses from three sarbecoviruses clades. Boosting with CoVEXS5 via systemic delivery elicited CD4+ lung-resident memory T cells, typically associated with mucosal immunisation strategies, which were not detected following mRNA-XBB boosting. Vaccination of hamsters with CoVEXS5 conferred significant protection against weight loss after SARS-CoV-1 challenge, compared to mRNA-XBB immunisation, that correlated with anti-SARS-CoV-1 nAbs in the sera of vaccinated animals. These findings highlight the potential of a chimeric spike antigen, formulated in an open-access adjuvant, as a next-generation vaccine candidate to enhance cross-protection against emerging sarbecoviruses in vaccinated populations globally.
下一代疫苗对于应对SARS-CoV-2不断演变的特性以及防范其他冠状病毒引发的新的大流行威胁至关重要。这些疫苗应能引发广泛的保护，提供持久的免疫力，并确保所有人群都能公平获得。在本研究中，我们开发了一组嵌合的全长刺突抗原，其纳入了先前流行的和预测的SARS-CoV-2变体的突变。主要候选疫苗（CoVEXS5）通过在稳定的中国仓鼠卵巢（CHO）细胞中进行的高产生产工艺制备，纯度>95%，显示出长期稳定性，并且当以角鲨烯乳液佐剂（Sepivac SWE™）递送至小鼠时能引发广泛交叉反应的中和抗体。在小鼠和仓鼠中，CoVEXS5免疫接种均能减轻SARS-CoV-2感染后的临床疾病症状、肺部炎症和器官病毒滴度，包括在受到高度免疫逃逸的奥密克戎XBB.1.5亚变体攻击后。在先前用已获许可的mRNA疫苗（Comirnaty XBB.1.5，称为mRNA-XBB）进行 primed的小鼠中，CoVEXS5加强免疫显著提高了针对三种沙贝病毒属分支病毒的中和抗体（nAb）水平。通过全身给药进行CoVEXS5加强免疫可引发CD4+肺驻留记忆T细胞，这通常与黏膜免疫策略相关，而在mRNA-XBB加强免疫后未检测到此类细胞。与mRNA-XBB免疫相比，用CoVEXS5对仓鼠进行疫苗接种可在SARS-CoV-1攻击后显著保护其免于体重减轻，这与接种疫苗动物血清中的抗SARS-CoV-1 nAb相关。这些发现突出了一种以开放获取佐剂配制的嵌合刺突抗原作为下一代疫苗候选物的潜力，以增强全球接种人群对新出现的沙贝病毒的交叉保护。
