On Target for Success
Many biotechs at the “World Vaccine Congress” had plenty of innovation to shout about, including Vaccibody. This spin-out from the University of Oslo showed off a twist on antibody technology that helps target vaccines to boost T-cell immunity.
“A vaccibody construct is a three-component antibody-like molecule,” Dr. Ole Henrik Brekke, Ph.D., CEO of Vaccibody, said. “It has a targeting unit that can be part of an antibody or binding ligand that attaches to surface molecules on antigen presenting cells (APC). The targeting unit is attached to a dimerization unit consisting of a hinge and CH3 domain from an immunoglobulin, so this section of the vaccibody even looks a bit like an antibody. Finally, the third part is the antigen or the vaccine unit.”
“Vaccibodies work by binding surface molecules on APCs,” Dr. Brekke continued. “The complex is taken up, and antigenic peptides are presented to CD4 or CD8 cells. The CD4 T cells secrete cytokines that help B cells develop into plasma cells that secrete huge amounts of antibodies. The CD8 and CD4 T cells as well as the antibodies generated eliminate the infectious agent or tumor cells they have been targeted against.”
To demonstrate proof of this concept, the company produced two types of vaccibodies containing pandemic flu and seasonal flu antigens. One is a normal targeting vaccibody and the other version has a mutation in the targeting unit so that it will not bind to APCs.
Dr. Brekke presented mouse model data that showed 100 days after vaccination, the targeted vaccibody generated IgG levels five times higher than the nontargeting vaccibody. The CD8 and CD4 levels measured by ELISPOT were five to eight times higher (respectively) than the nontargeted vaccibody, showing that targeting the vaccibody does promote T-cell immunity.
Additionally, 14 days after vaccination the mice injected with a vaccibody and challenged with a flu virus did not lose body weight compared to the unimmunized mice. The unimmunized mice showed drastically reduced weight and had to be sacrificed nine days after they were infected.
“As long as you know the gene sequence of the antigen you can easily exchange the vaccine unit so this type of vaccibody platform could be used to produce prophylactic or therapeutic vaccines against a range of diseases,” Dr. Brekke stated. “Vaccibody technology offers good safety, stability, and efficacy. Now that we have preclinical proof the vaccibodies work well we are seeking partners that would like to license this technology.”