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FH-Fc as a Pre-Exposure Prophylactic for Tickborne Disease

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R44AI152954-03
Agency Tracking Number: R44AI152954
Amount: $2,000,000.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: NIAID
Solicitation Number: PA21-259
Solicitation Year: 2021
Award Year: 2022
Award Start Date (Proposal Award Date): 2022-05-16
Award End Date (Contract End Date): 2024-04-30
Small Business Information
20980 Corsair Boulevard
Hayward, CA 94545-2740
United States
DUNS: 052917593
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (510) 887-1461
Business Contact
Phone: (510) 887-1461
Research Institution

Lyme disease (LD) is the most prevalent vector-borne disease in the United States, with up to 300,000
cases a year. LD is caused by several species of the spirochete bacteria Borrelia burgdorferi sensu lato (the
Lyme borreliae), which are transmitted by ticks from rodent reservoirs to human hosts. While a short course of
antibiotics is usually effective in eliminating the bacteria a sizeable number of LD patients continue to suffer long-
term, debilitating sequelae, including pain, fatigue, cognitive dysfunction and other symptoms known as post-
treatment Lyme disease (PTLD). As many as 1.9 million people in the US suffer from PTLD. There is currently
no vaccine that can prevent LD or PTLD.We are developing an immunoprophylactic for LD and other tick-borne diseases (TBD) based on an
understanding of the virulence mechanisms that the causal pathogens use to evade innate immunity. These
pathogens protect themselves from elimination by the human complement system by binding to the human
complement inhibitor Factor H (FH), a protein abundant in blood. FH bound to bacterial surfaces blocks the
activation of the alternative complement pathway that would otherwise destroy the bacteria. We have produced
recombinant proteins that are fusions of the FH domains that bind to Lyme borreliae with the constant region of
human IgG3 (Fc3), using a plant expression system. In Phase I we showed that the fusion SCR(6-7)/Fc3 binds
to B. burgdorferi (Bb) and B. afzelii (Ba) and, in the presence of human complement, kills the bacteria. We have
also demonstrated that SCR(6-7)/Fc3 prevents Bb and Ba infection in mice by blocking bacterial survival
in fed ticks and tick-to-host transmission at a dose as low as 2 mg/kg.Our overall goal is to develop a pre-exposure prophylactic (PrEP) to prevent LD and TBDs. In this Phase
II STTR project we will optimize the in vivo efficacy and pharmacokinetics of SCR(6-7)/Fc3. We will conduct
process development and carry out preliminary preclinical safety testing.The project is a collaboration of two research groups that are uniquely qualified to bring it to a successful
conclusion. Planet Biotechnology Inc (the small business concern) will produce novel variants of SCR(6,7)/Fc3.
Yi-Pin Lin at the New York State Department of Health will evaluate the ability of the proteins to mediate
complement-dependent killing of Lyme and relapsing fever spirochetes by membrane attack complex and
opsonophagocytosis by human macrophages and their ability to block infection when mice are bitten by ticks
carrying a virulent Lyme borreliae strain. We will select a lead FH-Fc pre-immune prophylaxis drug candidate,
scale up production, conduct toxicology studies in two animal species and analyze pharmacokinetics and
pharmacodynamics in humanized mice and non-human primates.

* Information listed above is at the time of submission. *

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