Current vaccines mostly contain inactivated or weakened bacteria/virus. However, this strategy cannot be used for protection against many of the pathogens presently causing concern (e.g. pandemic influenza, ebola). The solution is to use only selected proteins from these pathogens in vaccines, which is safe, but compromises vaccine efficacy. Here, we present a novel strategy for increasing the efficacy of such vaccines, and particularly antibody responses.
We have identified and extensively tested a novel targeting unit (scFv) that specifically can bind human HLA II molecules in the general population. Coupling of this targeting unit to an antigen will greatly increase efficacy of vaccination, and particularly for induction of antibodies (a known correlate of protection against most infectious diseases). The targeting unit binds a highly conserved site on HLA II molecules, and correspondingly also binds MHCII molecules in many larger animals. Thus, the targeting unit will be well suited to increase efficacy of vaccines aiming at antibody induction both for human and veterinary purposes.
Subunit vaccines (protein and DNA) typically suffer from low immunogenicity. However, targeting of antigens to specialized immune cells can increase efficacy, but have previously mostly been explored for increased T-cell immunity. Here, we have developed a targeting unit that targets antigen to HLA II molecules for induction of protective antibodies. Human HLA II molecules are highly variable, so our ability to bind a conserved region on these molecules is of paramount importance.
Previously, we have demonstrated that a single DNA vaccination can induce neutralizing antibodies against influenza both in ferrets and pigs (Figure 1) (Grødeland et al, J. Immunol 3575, 2016). Similar to influenza, antibodies represent an important correlate of protection against most infectious diseases. Thus, the HLA II-specific targeting unit is a highly interesting tool for targeting any antigen of interest to HLA molecules, with the aim of inducing strong antibody responses.
Neutralizing antibodies after one DNA vaccination in ferrets and pigs.
Ferrets and pigs were immunized once with painless jet delivery, and sera from animals at 29 days (ferret) or 21 days (pigs) assayed for neutralizing antibodies in an HI-assay. HLA II-targeted antigen was compared to antigen alone (HA), and a vaccine where the HLA II-specific scFv was exchanged with a scFv specific for the hapten NIP (non-targeted control vaccine). (Grødeland et al, J. Immunol 3575, 2016).
A patent application protecting the invention has been filed (US 62/352,815).
Further pre-clinical work is ongoing, and a clinical phase I trial is currently being planned.
We are seeking development partners and/or licensees for the technology.