Bionor’s strategy is to advance its proprietary therapeutic antibody vaccine – Vacc-C5 and its t-cell vaccine – Vacc-4x as a combined vaccine together with appropriate adjuvants to boost both arms of the immune system. The antibodies from Vacc-C5 will control/block viral replication while Vacc-4x will kill viral reservoirs.
Studies of patients known to be long-term non-progressors, (HIV patients in which the disease does not advance rapidly) show that those with elevated antibody levels that are binding to Vacc-C5 have lower viral load and lower immune activation than patients not having such antibodies.
Furthermore, preclinical data show that immunization with Vacc-C5 in several species can elicit high antibody titers and an overall robust antibody profile indicating to researchers that these antibodies will reduce/prevent an increased immune activation and reduce viral load when the combination antiretroviral therapy (cART) medications are removed in humans. Furthermore, there are several reasons for researchers to believe that high antibody titers to Vacc-C5 are expected to reduce the viral fitness of viruses that have come out in circulation significantly and could even lead to neutralizing of the virus completely (see Vacc-C5 mechanism of action).
Immunizations with Vacc-4x in humans show that immunological pressure from T-cell/CTL responses from Vacc-4x makes HIV less replication fit and reduces viral load significantly. Researchers have reasons to believe that the addition of antibodies from Vacc-C5 will, however, reduce/limit the initial viral production boost and enable CTL from Vacc-4x to kill cells that are about to start producing HIV (see Vacc-4x mechanism of action).
Researchers have also reasons to believe that anti Vacc-C5 antibodies in circulation will as backup be able to pick up and remove those viruses that may have circumvented Vacc-4x CTL’s and have been released to the bloodstream.
Bionor researchers have therefore reasons to believe that the synergies from this combined strategy will lead to a viral load is below 50 copies of HIV-RNA per ml for a prolonged period of time
Bionor will as part of this development strategy seek regulatory path advice to optimize timelines and development costs towards a market approval.
Why Pursue a Functional Cure
A “Functional Cure” is defined as the ability of an HIV positive individual to have mediated control of HIV replication, in the absence of cART. In the course of a functional cure, the virus in the blood is controlled at a level low enough to prevent disease progression and transmission.
However, it is of interest to also enable a long-term reduction in viral reservoirs. Bionor’s shock and kill strategy will be pursued as a shock, block and kill strategy. We will begin by conducting smaller studies to develop an understanding of how this treatment candidate impacts reservoirs and how to define thresholds that can also lead to additional clinical benefit.
The International AIDS Society considers cure research as a worthwhile approach stating: “A safe, affordable and scalable cure will improve the health and quality of life for those with established infection, reduce the risk of viral transmission to those not infected and ultimately allow resources to be shifted to other needs. A cure will thus achieve what preventive and therapeutic approaches aim to do, which is to essentially stop transmission of HIV to those who are uninfected and restore immunological function and normal health to those who are infected.”
Functional cure was first attempted by Jonas Salk 30 years ago, however, due to the vast amount of challenges there are currently no common recommendations with regard to regulatory requirements for clinical studies or marketing authorizations in this area unless the aim of the functional cure is to stabilize the viral load below 50 copies of HIV RNA/milliliter in the absence of cART for a prolonged period of time.
The feasibility of an HIV functional cure strategy is supported by clinical evidence that some HIV infected individuals are able to achieve natural and persistent control of viral replication (i.e., HIV RNA <50 copies/milliliter) in the absence of cART. These “elite controllers” show a low concentration of HIV DNA in different subsets of circulating CD4+ T cells in blood as well as in rectal tissue, both indicating that these patients have lower HIV viral reservoir.
Pill burden and side effects are part of life for people living with HIV. A functional cure will be a leap forward in the quality of life for those on treatments and for those who are suffering from pill fatigue/burden and side effects after years of daily treatment. It may also be more accessible for a larger part of those are HIV positive but do not have access to therapy.