Pellis Therapeutics aims to bring to market products based on the immunological platform technology developed by Dr. Thomas Kupper and his team at Harvard/Brigham and Women’s hospital.  Over the last 15 years Doctor Kupper’s NIH/NIAID-supported work has explored the unique immunological properties of the skin and other barrier tissues, which form the body’s first line of defense against infection by pathogens.  Skin is now understood to harbor a large and diverse population of immune cells primed to generate an especially strong and durable protective T cell response (cellular immunity) in both skin and lung tissue, while also eliciting a strong B cell (humoral immunity) antibody response to viral and other pathogens.  Targeting this T cell response against skin and lung cancer antigens should also prove beneficial to the management of those diseases.

The Pellis platform uses safe, non-replicating strains of vaccinia (poxvirus) vectors to encode selected antigens.  When delivered into the skin specifically through a process of epidermal disruption at the vaccination site, where high throughput administration will use a proprietary device, the resulting local tissue effects together with the vector’s adjuvant property, specific to the poxvirus family and triggered by injury to the skin, stimulates the production of skin- and lung-homing effector and memory T cells.  Pellis owns the platform patent on this route of delivery for non-replicating poxvirus-vectored vaccines.

Vaccine development has historically been focused on producing neutralizing antibody responses, which have the advantage of being easy to measure.  Yet once a virus or other pathogen has entered a cell it becomes invisible to circulating antibodies and can only be eliminated by the destruction of the infected cell by cytotoxic CD8+ T cells, the effectors of cellular immunity.  Pellis’ T cell-focused vaccine platform is capable of generating both cellular (T cell) and humoral (antibody) immune memory.

The structures expressed on a pathogen’s surface are its only antigens exposed to potentially neutralizing antibodies and are the targets for conventional antibody-focused vaccines.  In contrast, cellular immunity may also be triggered by internal viral core proteins, fragments of which are presented on the surfaces of infected cells.  As a result, T cell focused vaccines allow greater latitude in vaccine payload selection, and in particular they allow the selection of internal viral proteins whose essential functions lead them to be highly conserved across all related viruses.  Thus T cell-focused vaccines have the potential of providing broad and even universal coverage across a given genus of virus, along with protection against antigenic drift and the year-to-year variability of the targeted antigen.

In this vein, Pellis Therapeutics’ lead products in development are a universal influenza vaccine for influenza A, now undergoing extensive preclinical testing and analysis, and a universal betacoronavirus vaccine against COVID-19, also in preclinical testing.

The Pellis vaccination platform, with its generation of lung tissue-resident and -homing T cells, is particularly well-suited to address the COVID-19 pandemic, where the relative importance of cellular immunity as opposed to antibodies is becoming increasingly clear.  For example, antibody titers against coronaviruses have not proven durable, while T cell memory against closely-related SARS has been shown to be strong after 17 years.  COVID-19 patients whose antibody response is altered genetically or therapeutically, but whose cellular immunity is intact, have recovered without suffering severe disease.  SARS-CoV-2 has been implicated as spreading directly from cell-to-cell within tissues, inaccessible to antibody but vulnerable to cytotoxic T cells.  Blood from up to half of COVID-19 uninfected individuals, including samples drawn in earlier years, has been shown to contain T cells that are reactive to antigens conserved between SARS-CoV-2 and other circulating "common cold" betacoronaviruses.  It is suspected that such serendipitous partial preexisting T cell immunity may influence the highly variable course of COVID-19, which ranges from asymptomatic to lethal.

In generating our COVID-19 vaccine candidates, we have selected conserved proteins that are expressed early in the process of viral replication within infected cells, which should allow those cells to be destroyed prior to maturation of the virus.  Pellis has candidates both with and without the Spike protein that is ubiquitous in conventional COVID-19 vaccine efforts focused on generating neutralizing antibody responses to Spike.  Because the Pellis platform induces strong antibody as well as T cell responses, our candidates that include Spike should do well on that metric.  Significantly, our candidates that contain only conserved proteins internal to the virus and inaccessible to antibodies should not carry the risk of antibody-dependent disease enhancement (ADE) according to the current understanding of that phenomenon.  This, and the safety history of the Modified Vaccinia Ankara vectors we use, contribute to the safety of the Pellis vaccination platform.

Beyond universal influenza and betacoronavirus vaccines, we believe the Pellis platform is suitable to other unmet vaccination needs, including respiratory syncytial virus and tuberculosis.  We believe the production of skin and lung tissue-resident T cells will also be relevant to skin and lung cancers, particularly in conjunction with checkpoint inhibitors.  Finally, the company plans to pursue small molecule therapeutics for autoimmune conditions related to tissue-resident T cells.

Contact:  Eric Stromquist, estromquist@pellistx.com