A Formulated TLR7/8 Agonist is a Flexible, Highly Potent and Effective Adjuvant for Pandemic Influenza Vaccines

Since 1997, highly pathogenic avian influenza viruses of the H5N1 subtype have been transmitted from avian hosts to humans. The severity of H5N1 infection in humans, as well as the sporadic nature of H5N1 outbreaks, both geographically and temporally, make generation of an effective vaccine a global...

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Published in:Scientific reports 2017-04, Vol.7 (1), p.46426-46426, Article 46426
Main Authors: Van Hoeven, Neal, Fox, Christopher B., Granger, Brian, Evers, Tara, Joshi, Sharvari W., Nana, Ghislain I., Evans, Sarah C., Lin, Susan, Liang, Hong, Liang, Li, Nakajima, Rie, Felgner, Philip L., Bowen, Richard A., Marlenee, Nicole, Hartwig, Airn, Baldwin, Susan L., Coler, Rhea N., Tomai, Mark, Elvecrog, James, Reed, Steven G., Carter, Darrick
Format: Article
Language:English
Subjects:
13/1
13/31
38/79
631/250/590/2291
631/326/596/1578
Animal models
Antigens
Avian flu
Clinical trials
Disease transmission
Hemagglutinins
Humanities and Social Sciences
multidisciplinary
Outbreaks
Pandemics
Public health
Science
TLR7 protein
Toll-like receptors
Vaccines
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Summary:Since 1997, highly pathogenic avian influenza viruses of the H5N1 subtype have been transmitted from avian hosts to humans. The severity of H5N1 infection in humans, as well as the sporadic nature of H5N1 outbreaks, both geographically and temporally, make generation of an effective vaccine a global public health priority. An effective H5N1 vaccine must ultimately provide protection against viruses from diverse clades. Toll-like receptor (TLR) agonist adjuvant formulations have a demonstrated ability to broaden H5N1 vaccine responses in pre-clinical models. However, many of these agonist molecules have proven difficult to develop clinically. Here, we describe comprehensive adjuvant formulation development of the imidazoquinoline TLR-7/8 agonist 3M-052, in combination with H5N1 hemagglutinin (HA) based antigens. We find that 3M-052 in multiple formulations protects both mice and ferrets from lethal H5N1 homologous virus challenge. Furthermore, we conclusively demonstrate the ability of 3M-052 adjuvant formulations to broaden responses to H5N1 HA based antigens, and show that this broadening is functional using a heterologous lethal virus challenge in ferrets. Given the extensive clinical use of imidazoquinoline TLR agonists for other indications, these studies identify multiple adjuvant formulations which may be rapidly advanced into clinical trials in an H5N1 vaccine.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep46426