About VLP Vaccines
Virus-like particle (VLP) vaccines have the potential to be a best-in-class, second generation vaccine that can deliver safe, effective, and durable protection with a single dose. VLPs are multiprotein structures that mimic viruses but lack the viral genome. Because they contain no genetic material, they are non-infectious and can potentially provide a safer alternative to other vaccine technologies.
IVX-121: RSV VLP Vaccine Candidate
IVX-121 targets respiratory syncytial virus (RSV), a major cause of viral pneumonia for which no vaccine has been FDA approved. IVX-121 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.
About RSV and Older Adults
For older adults, RSV can be a life-threatening respiratory infection, with comparable 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 million–$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.
IVX-411: SARS-CoV-2 VLP Vaccine Candidate
IVX-411 targets SARS-CoV-2, the coronavirus that causes COVID-19. Developed using cutting-edge structure-based design techniques at the Institute for Protein Design at the UW School of Medicine, IVX-411, our lead vaccine candidate for COVID-19, is a self-assembling protein nanoparticle that displays 60 copies of the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain (RBD) in a highly immunogenic array.
Preclinical data from University of Washington and their collaborators show IVX-411 induces high neutralizing antibody titers in mice after a single administration and further improvement after a second administration (Cell 2020). Titers after the second administration were ten-fold higher than those seen with the soluble SARS-CoV-2 spike protein that forms the basis of many other vaccine candidates. The data also show a strong B-cell response after immunization, critical for immune memory and a durable vaccine effect, with antibodies that target multiple distinct epitopes on the RBD, suggesting potential protection from escape mutations.
Icosavax has received a $10 million grant from the Bill & Melinda Gates Foundation to support the company’s COVID-19 vaccine program through the first in human Phase 1 clinical trial in young and older adults. Clinical trials are expected to initiate in mid-2021.
About COVID-19 and Older Adults
Adults over 65 account for over 75% of all COVID-19 deaths in the U.S.
“It’s clear that we will need a variety of vaccine approaches to effectively fight this novel coronavirus. That’s why it’s important to advance not just the fastest but the best vaccine technologies that can deliver safe, effective, and durable protection.”
Jean-Paul Prieels, Ph.D., former Senior Vice President of Research and Development at GSK Vaccines and member of the scientific advisory board of Icosavax
COVID-19 symptoms can range from no symptoms to severe illness. Older adults and people of any age who have serious underlying medical conditions may be at higher risk for more severe illness. Vaccines are especially important for older adults, as their immune systems weaken (immunosenescence) making it more difficult to fight off infections. This can lead to long-term illness and life-threatening complications; adults over 65 account for over 75% of all COVID-19 deaths in the U.S. (CDC). Most currently used vaccines are less immunogenic and effective in the elderly compared to younger adults. Thus new vaccine technologies that can deliver higher immunogenicity and greater efficacy are greatly needed, especially for older adults.