Virus-like Particles (VLPs)
VLPs enable high-density, multivalent display of antigens in a manner that closely resembles viruses, with an important difference. VLPs contain no genetic material, so they are non-infectious and can provide a safer alternative to live-attenuated or inactivated vaccines. Naturally occurring VLPs have delivered successful vaccines, including Gardasil® and Cervarix® against human papillomavirus (HPV) and Engerix-B® and Recombivax HB® against Hepatitis B. However, VLPs have been difficult to use for the display of complex heterologous antigens, like in the case of RSV.
Computationally Designed VLPs
Founded on technology developed at the Institute for Protein Design (IPD) at the University of Washington, Icosavax’s technology solves the problem of constructing and manufacturing VLPs displaying complex antigens by utilizing computationally designed proteins that separate the folding of individual protein subunits from the assembly of the final macromolecular structure. The individual proteins are expressed and purified using traditional recombinant technologies, and then self-assemble into VLPs when mixed together. VLPs are known to induce superior immunological responses compared to traditional soluble antigens, eliciting protective immune responses while reducing the need for strong adjuvants, which in some instances have been associated with side effects.
IVX-121, our lead vaccine candidate for respiratory syncytial virus (RSV), incorporates a stabilized prefusion F antigen licensed from NIAID/NIH (DS-Cav1; Science 2019). RSV F is known to undergo major structural changes that allow viral entry into the host cell, and during that process, critical protective epitopes are lost. Protein design methods have stabilized prefusion F, leading to improved neutralizing responses in humans.
Our VLP technology further enhances the magnitude, quality, and durability of the response to prefusion RSV F, as shown in extensive preclinical studies conducted at IPD (Cell 2019) and Icosavax. The enhanced response to VLP-based prefusion F could be particularly important in older adult populations that show reduced responsiveness to conventional vaccines due to immunosenescence and is expected to translate into a superior product profile.
Crank MC, et al. A proof of concept for structure-based vaccine design targeting RSV in humans. Science (2019), 505-509.
Rappuoli R. and D. Serruto. Preview: Self-Assembling Nanoparticles Usher in a New Era of Vaccine Design. Cell (2019), 1245-1247.
Our technology allows us to readily manufacture virus-like particles (VLPs) displaying complex antigens to target a whole class of vaccine targets with significant unmet medical needs.
For older adults, RSV can be a life-threatening respiratory infection, with comparable rates of infection and severity to that of influenza.
Respiratory syncytial virus (RSV) causes infection of the respiratory tract, with symptoms that can sometimes be confused with influenza. It is a ubiquitous pathogen that infects 100% of the population by age 2. With outbreaks each year during the Northern Hemisphere winter, RSV is a major viral cause of pneumonia, which is most severe in infants and young children and in older adults (NEJM, 2005). Worldwide, RSV disease affects an estimated 64 million people and causes 160,000 deaths each year (NIAID). There are no specific antiviral therapies or vaccines for RSV.
In the United States, it is estimated that more than 177,000 older adults are hospitalized, and 14,000 of them die due to RSV infection (CDC). The highest burden of RSV healthcare costs in the United States are in those aged ≥65 years (PLoS One, 2017). Estimates of total RSV-attributable healthcare costs for all elderly aged ≥65 years in the United States range $150–680 million to $1 billion (BMC Health Services Research, 2018).
The global cost in lives and health care expenditures is significant, especially amongst the very young and very old, and a vaccine solution is desperately needed.