Intranasal Vaccine Against Lyme Disease

ABSTRACT We propose to develop intranasal, parainfluenza 5 (PIV5) viral-vector delivered vaccines against human Lyme disease (LD) to be administered using a prime-boost schedule, for the US market. A recent new estimate of LD by the CDC places the new number at 476,000 annual cases, up from 329,000 in 2015 which strongly suggests that the number of Americans affected by this vector-borne disease is increasing. Currently, there is no human Lyme Disease vaccine available in the market. A prime-boost vaccination with an intranasal immunogen is a scientific and technologic advance over best vaccination protocols in development for LD that currently rely on parenteral inoculation of a minimum of 3 doses over 1 year. Our preliminary studies show that intranasal administration of a modified OspA vaccine delivered by the laboratory strain WR-PIV5 viral vector (WR-PIV5-OspABPBPk) via prime-boost (2 doses), produces an immune response that is 100% protective against tick transmitted B. burgdorferi infection in mice challenged 4 months after the 1st dose. PIV5 is a safe delivery vector used to develop many vaccines, one of which is undergoing a human clinical trial. The commercialization potential and societal impact of developing a novel, safe and efficacious LD vaccine that can be delivered by a non-invasive method is highly significant given that it may induce more durable immune responses, it could diminish vaccine hesitancy and increase vaccine compliance, and it could enable self-administration of one or both doses. The novelty of the vaccine proposed in this Direct to Phase II SBIR application relates to: 1) the use of a modified full length OspA protein in which the putative autoantigenic epitope has been replaced; 2) a needle-free intranasal delivery method in a safe, highly immunogenic viral vector; 3) the reduced number of immunizations; 4) ease of administration; and 5) the potential to increase immunity longevity. We propose to develop a new viral vector expressing OspABPBPk based on the PIV5 vaccine strain (CPI) and evaluate intranasal vaccine efficacy in mice as compared to the WR-PIV5- ABPBPk shown in preliminary results; we will also assess immunogenicity, safety and efficacy of the best vaccine candidate in the non-human primate (NHP) model of Lyme disease; last, we will perform studies required for Investigational New Drug (IND) regulatory approval by FDA. Once the novel vaccine is shown to meet pre-set performance criteria specified in our milestones (>80% efficacy in mice and non-human primate models), it will be trademarked as LymeMist™ and the company will implement a plan to commercialize it.