Janitzek Christoph M, Carlsen Philip H R, Thrane Susan, Khanna Vijansh M, Jakob Virginie, Barnier-Quer Christophe, Collin Nicolas, Theander Thor G, Salanti Ali, Nielsen Morten A, Sander Adam F
Centre for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, 1165 København, Denmark.
Department of Infectious Diseases, Copenhagen University Hospital, 2100 Copenhagen, Denmark.
Vaccines (Basel). 2021 Feb 6;9(2):131. doi: 10.3390/vaccines9020131.
Capsid-like particle (CLP) displays can be used to enhance the immunogenicity of vaccine antigens, but a better understanding of how CLP vaccines are best formulated and delivered is needed. This study compared the humoral immune responses in mice elicited against two different vaccine antigens (a bacterial protein and a viral peptide) delivered on an AP205 CLP platform using six different adjuvant formulations. In comparison to antibody responses obtained after immunization with the unadjuvanted CLP vaccine, three of the adjuvant systems (neutral liposomes/monophosphoryl lipid A/quillaja saponaria 21, squalene-in-water emulsion, and monophosphoryl lipid A) caused significantly increased antibody levels, whereas formulation with the three other adjuvants (aluminum hydroxide, cationic liposomes, and cationic microparticles) resulted in similar or even decreased antibody responses. When delivering the soluble bacterial protein in a squalene-in-water emulsion, 4-log lower IgG levels were obtained compared to when the protein was delivered on CLPs without the adjuvant. The AP205 CLP platform promoted induction of both IgG1 and IgG2 subclasses, which could be skewed towards a higher production of IgG1 (aluminum hydroxide). Compared to other routes, intramuscular administration elicited the highest IgG levels. These results indicate that the effect of the external adjuvant does not always synergize with the adjuvant effect of the CLP display, which underscores the need for empirical testing of different extrinsic adjuvants.
衣壳样颗粒(CLP)展示可用于增强疫苗抗原的免疫原性,但需要更好地了解如何优化CLP疫苗的配方和递送方式。本研究比较了在AP205 CLP平台上使用六种不同佐剂配方递送的两种不同疫苗抗原(一种细菌蛋白和一种病毒肽)在小鼠中引发的体液免疫反应。与未加佐剂的CLP疫苗免疫后获得的抗体反应相比,三种佐剂系统(中性脂质体/单磷酰脂质A/皂树皂苷21、水包角鲨烯乳液和单磷酰脂质A)导致抗体水平显著升高,而使用其他三种佐剂(氢氧化铝、阳离子脂质体和阳离子微粒)配方则导致相似甚至降低的抗体反应。当在水包角鲨烯乳液中递送可溶性细菌蛋白时,与在无佐剂的CLP上递送该蛋白相比,获得的IgG水平低4个对数。AP205 CLP平台促进了IgG1和IgG2亚类的诱导,这可以偏向于更高水平的IgG1产生(氢氧化铝)。与其他途径相比,肌肉内给药引发的IgG水平最高。这些结果表明,外部佐剂的作用并不总是与CLP展示的佐剂作用协同,这突出了对不同外部佐剂进行实证测试的必要性。