Carbopol dispersed PAA-modified UIO-66 with high colloidal stability as a combination nano-adjuvant boosts immune response and protection against pseudorabies virus in mice and pigs

Abstract

Although inactivated vaccines have higher safety than live-attenuated vaccines in the control of pseudorabies virus (PRV), their protection efficacy is limited due to insufficient immunogenicity when used alone. High-performance adjuvants that can potentiate immune responses are highly desirable to improve the protection efficacy of inactivated vaccines. In this work, we have developed U@PAA-Car, a Carbopol dispersed zirconium-based metal-organic framework UIO-66 modified by polyacrylic acid (PAA), as a promising adjuvant for inactivated PRV vaccines. The U@PAA-Car has good biocompatibility, high colloidal stability, and antigen (vaccine) loading capacity. It significantly potentiates humoral and cellular immune responses over either U@PAA, Carbopol, or commercial adjuvants such as Alum and biphasic 201 by inducing a higher specific antibody titer, IgG2a/IgG1 ratio, cell cytokine secretion, and splenocyte proliferation. A protection rate of over 90% was observed in challenge tests in the model animal mice and the host animal pigs, which is much higher than that observed with commercial adjuvants. The high performance of the U@PAA-Car is attributed to antigen sustainable release at the injection site and highly efficient antigen internalization and presentation. In conclusion, this work not only demonstrates a great potential of the developed U@PAA-Car nano-adjuvant for the inactivated PRV vaccine but also gives a preliminary explanation of its action mechanism. STATEMENT OF SIGNIFICANCE: We have developed a Carbopol dispersed PAA-modified zirconium-based metal-organic framework UIO-66 (U@PAA-Car) as a promising combination nano-adjuvant for the inactivated PRV vaccine. The U@PAA-Car induced higher specific antibody titers and IgG2a/IgG1 ratio, increased cell cytokines secretion, and better splenocyte proliferation than U@PAA, Carbopol, and the commercial adjuvants Alum and biphasic 201, indicating that it induces a significant potentiation of humoral and cellular immune response. In addition, much higher protection rates were achieved with the U@PAA-Car-adjuvanted PRV vaccine in mice and pigs challenge than those observed from the commercial adjuvant groups. This work not only demonstrates the great potential of the U@PAA-Car nano-adjuvant in an inactivated PRV vaccine but also gives a preliminary explanation of its action mechanism.

Keywords: Immune response; Metal-organic framework; Nano-adjuvant; Pseudorabies virus.