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Learning from the Ebola success: Can a mAb also save lives after yellow fever infection?

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R42AI155275-01
Agency Tracking Number: R42AI155275
Amount: $299,598.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAID
Solicitation Number: PA19-270
Solicitation Year: 2019
Award Year: 2020
Award Start Date (Proposal Award Date): 2020-07-02
Award End Date (Contract End Date): 2021-06-30
Small Business Information
Miami, FL 33133-5155
United States
DUNS: 080802534
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (503) 418-2774
Business Contact
Phone: (305) 322-4561
Research Institution
PORTLAND, OR 97239-3098
United States

 Nonprofit College or University

The recent groundbreaking experiment using a single neutralizing monoclonal antibody (nmAb) to reduce
the death rate in Ebola virus (EBOV)-infected individuals highlights the importance of this class of drug in
the treatment of infectious disease. In August 2019, Dr. Anthony Fauci announced that administration of
mAb114 had reduced the death rate from 70% to approximately 35% in EBOV-infected patients. EBOV infection
is no longer considered a uniformly fatal disease. Similar to EBOV infection, wild-type yellow fever virus
(wtYFV) infection results in high viral loads and a death rate of up to 50% in hospitalized patients. Once
infected, there is no current treatment available. While the YFV17D vaccine is generally efficacious, it has
some potentially severe side effects which diminish its coverage. Unfortunately, the World Health Organization
(WHO) reported approximately 100 cases of severe adverse effects due to mass vaccination campaigns
in Brazil, dissuading many people from receiving the vaccine. Even though vaccination campaigns were
launched, immunization coverage remains low, leaving a significant number of people at risk. Most of the
world, including the U.S., is vulnerable to mosquito-transmitted diseases, as shown by the emergence of two
related flaviviruses dengue (DENV) and Zika (ZIKV).
At Mabloc LLC, through our collaborations with the Watkins, Kallas and Burton laboratories, and Adimab LLC,
we have assembled a large collection of flavivirus-specific neutralizing monoclonal antibodies (nmAbs).
Indeed, the Watkins laboratory has already shown that these mAbs can be used for the prevention and
treatment of flavivirus infections. The Watkins and Burton laboratories, and more recently others, have
demonstrated that ZIKV infection can be prevented in Indian rhesus macaques by using either a nmAb cocktail
or a single nmAb. Additionally, the Watkins and Burton laboratories have also shown that this cocktail can reduce
viral load to undetectable levels in ZIKV-infected pregnant macaques. These data demonstrated, for the
first time, that post-exposure treatment with nmAbs can reduce flavivirus replication in a relevant non-
human primate (NHP) model.
In Phase I of this application, we plan to identify at least five nmAbs from our existing pool of mAbs for
wtYFV treatment using in vitro assays and in vivo screening in Syrian golden hamsters. In Phase II, we will
perform tissue cross reactivity studies using our best YFV-specific nmAbs. We will then test the efficacy of
the best three nmAbs in treating wtYFV-infected monkeys.
After the completion of this Fast-Track Phase I/II application, we plan to have at least a commercially
viable cocktail or a single nmAb that can efficaciously suppress viral replication in wtYFV-challenged
NHPs, and thereby save them from the sequelae of wtYFV infection, namely death.PROJECT NARRATIVE
The recent outbreaks of fatal yellow fever virus infections are causing alarm and vaccine shortages worldwide.
Nearly one billion people are at risk of yellow fever infection and, once infected, there is no current treatment
available for this disease. We plan to use neutralizing monoclonal antibodies to prevent this normally fatal

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

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