With support from the Division of Microbiology and Infectious Diseases (DMID) at the NIH, BlueWillow is conducting studies to develop NE vaccine-induced intravenous immunoglobulin (IVIG) for RSV. The product will be developed with the goal of treating and/or preventing RSV infection in premature babies, infants and the elderly, in addition to providing the many benefits of standard IVIG.
Respiratory syncytial virus (RSV) is a respiratory disease that causes serious infection of the respiratory tract. In certain cases, RSV infection can become quite severe, leading to hospitalization or even death. Similar to influenza, RSV transmission rates peak seasonally each year, with approximately 2.5 million infections occurring annually in the United States.
RSV infection is particularly concerning for premature babies, infants and the elderly population. Globally each year, over 64 million infections occur in infants and young children leading to 160,000 deaths. In those over 65 years of age, it is responsible for over 200,000 hospitalizations and 16,000 deaths annually. Currently, there is no approved RSV vaccine available and there is no therapy approved to treat or prevent infection.
BlueWillow’s NE-RSV vaccine candidate has demonstrated robust immunogenicity and protection in numerous studies conducted to date in mice and cotton rats. In its upcoming Phase 1 studies, the company plans to vaccinate plasma donors with its NE-RSV vaccine, which will allow it to derive and fractionate plasma for the development of hyperimmune RSV IVIG.
BlueWillow’s NE-RSV Vaccine
BlueWillow’s RSV vaccine candidate combines the company’s proprietary NE adjuvant with its proprietary whole virus RSV antigen (L19 strain). Given the NE has inherent antimicrobial properties, formulation of the adjuvant with L19 splits and fully inactivates the RSV virus. Total viral inactivation occurs within one hour of formulation, as shown in the chart below:
Use of the NE to split and inactivate the RSV virus maintains the integrity and nativity of the viral surface proteins. This is in stark contrast to chemical inactivation that is used for other whole killed RSV vaccine candidates. As shown in the diagram below, the use of agents such as formalin or β-PL will maintain the structure of the virus but will chemically alter and potentially damage the native viral epitopes:
Chemical inactivation of RSV can negatively impact the immune responses elicited by the whole killed vaccine as demonstrated in the charts below. The charts compare the immunogenicity elicited by an IM NE-inactivated RSV vaccine to an IM alum formalin-inactivated RSV vaccine. It is clear that the NE-inactivated vaccine elicits markedly higher functional antibody responses:
In a subsequent challenge study in cotton rats, the IM NE RSV vaccine elicited robust immune responses and protected all animals from RSV infection:
Benefits of NE-RSV IVIG
As mentioned above, there is no approved vaccine for RSV and there are no therapies approved to treat or prevent RSV infection. The only therapy currently available is a monoclonal antibody that is approved for the prevention of serious lower respiratory tract disease caused by RSV in pediatric patients at high risk of RSV disease.
NE-vaccine induced IVIG offers several significant potential benefits over the current monoclonal antibody therapy, including:
- The NE vaccine is formulated with the whole L19 RSV virus, and thereby incorporates all of the antigens from RSV as opposed to a single antibody;
- BlueWillow’s proprietary L19 RSV strain has been shown to produce 5x the F protein compared to other RSV strains;
- The vaccine induces both pre-fusion and post-fusion F-protein antibodies;
- Since the NE serves to inactivate RSV, the vaccine preserves the native viral epitopes which leads to the production of high avidity neutralizing antibodies as demonstrated in the animal studies summarized above; and,
- In addition to providing hyperimmune RSV antibodies, NE-RSV IVIG will confer the qualities and therapeutic effect of standard IVIG, which is a mainstay therapy for premature babies and infants or elderly patients that are immunodeficient.
BlueWillow’s composition patent covering the NE-RSV IVIG therapy has issued, with an expiration date in July 2032.