CYT-004-MelQbG10

Carbonic anhydrase IX (CAIX) is a cancer-associated membrane protein frequently overexpressed in hypoxic solid tumours leading to enhanced tumour cell survival and invasion, and it has been proposed to be an attractive tumour-specific molecule for antibody-mediated targeting. This study aimed to generate a virus-like particle (VLP)-based CAIX vaccine candidate and evaluate its efficacy in a mouse model of breast cancer. The prototype murine vaccine was developed based on the ssRNA bacteriophage Qbeta VLPs with chemically coupled murine CAIX protein catalytic domains on their surfaces. The vaccine was shown to efficiently break the natural B cell tolerance against autologous murine CAIX and to induce high-titre Th1-oriented IgG responses in the BALB/c mice. This vaccine was tested in a therapeutic setting by using a triple-negative breast cancer mouse model system comprising 4T1, 4T1-Car9^KI and 4T1-Car9^KO cells, the latter representing positive and negative controls for murine CAIX production, respectively. The humoural immune responses induced in tumour-bearing animals were predominantly of Th1-type and higher anti-mCAIXc titres correlated with slower growth and lung metastasis development of 4T1 tumours constitutively expressing mCAIX in vivo in the syngeneic host.

Infectious bronchitis (IB) Gammacoronavirus causes a highly contagious respiratory disease in chickens that is listed by the World Organisation for Animal Health (WOAH). Its high mutation ability has resulted in numerous variants against which the commercially available live or recombinant vaccines singly offer limited protection. Agrobacterium-mediated transient expression in Nicotiana benthamiana (tobacco) plants was used here to produce a virus-like particle (VLP) vaccine expressing a modified full-length IBV spike (S) protein of a QX-like IB variant. In a challenge study with the homologous live IB QX-like virus, VLP-vaccinated birds produced S protein-specific antibodies comparable to those produced by live-vaccinated birds seroconverting with mean geometric titers of 6.8 and 7.2 log₂, respectively. The VLP-vaccinated birds had reduced oropharyngeal and cloacal viral shedding compared to an unvaccinated challenged control and were more protected against tracheal ciliostasis than the live-vaccinated birds. While the results appeared similar, plant-produced IB VLPs are safer, more affordable, easier to produce and update to antigenically match any emerging IB variant, making them a more suitable alternative to IBV control than live-attenuated vaccines.