GLA-AF, an Emulsion-Free Vaccine Adjuvant for Pandemic Influenza

Abstract

The ongoing threat from Influenza necessitates the development of new vaccine and adjuvant technologies that can maximize vaccine immunogenicity, shorten production cycles, and increase global vaccine supply. Currently, the most successful adjuvants for Influenza vaccines are squalene-based oil-in-water emulsions. These adjuvants enhance seroprotective antibody titers to homologous and heterologous strains of virus, and augment a significant dose sparing activity that could improve vaccine manufacturing capacity. As an alternative to an emulsion, we tested a simple lipid-based aqueous formulation containing a synthetic TLR4 ligand (GLA-AF) for its ability to enhance protection against H5N1 infection. GLA-AF was very effective in adjuvanting recombinant H5 hemagglutinin antigen (rH5) in mice and was as potent as the stable emulsion, SE. Both adjuvants induced similar antibody titers using a sub-microgram dose of rH5, and both conferred complete protection against a highly pathogenic H5N1 challenge. However, GLA-AF was the superior adjuvant in ferrets. GLA-AF stimulated a broader antibody response than SE after both the prime and boost immunization with rH5, and ferrets were better protected against homologous and heterologous strains of H5N1 virus. Thus, GLA-AF is a potent emulsion-free adjuvant that warrants consideration for pandemic influenza vaccine development.

Protection and Long-Lived Immunity Induced by the ID93/GLA-SE Vaccine Candidate against a Clinical Mycobacterium tuberculosis Isolate

“…GLA adjuvant formulations have been used with experimental vaccines for influenza, HIV (29), respiratory syncytial virus (RSV) (30), leishmaniasis (31), malaria (32), and leprosy (33) in addition to TB (34,35). Many of these vaccines using GLA formulations have also resulted in protection in preclinical animal models, including mice (34)(35)(36), ferrets (37,38), guinea pigs (34,35,39), cotton rats (30), and hamsters (40), against infectious challenge.…”

In vitro cytokine induction by TLR-activating vaccine adjuvants in human blood varies by age and adjuvant

“…In this study we employed a whole blood assay (WBA) to study the ontogeny of cytokine responses to four TLRAs: monophosphoryl lipid A (MPLA; TLR4), an aqueous formulation the novel glucopyranosyl lipid antigen (GLA-AF; TLR4) [33, 34], resiquimod (R848; TLR7/8) and CpG oligonucleotide ODN 2395 (TLR9). Although both MPLA and GLA are based on the core lipid A of LPS, there are important differences between these two molecules, including that the latter is synthetic [34].…”

Selection of therapeutic H5N1 monoclonal antibodies following IgVH repertoire analysis in mice

“…However, several studies have shown that these types of antibodies can be induced following heterologous primeboost vaccination and by using vaccine adjuvants that broaden heterosubtypic Ab responses (Buricchi et al, 2013; Chiu et al, 2013; Li et al, 2013). Thus, to enrich for cross-reactive Abs, mice were immunized with rHA isolated from 2 Group 1 HA viruses, VN1203 and CA07 virus, in the presence of the TLR4 adjuvant GLA-SE, which increases antibody repertoire diversity and enhances protection against heterosubtypic strains of H5N1 virus in mice and ferrets (Clegg et al, 2014; Clegg et al, 2012; Wiley et al, 2011). Antisera were then tested for their ability to bind to their cognate antigen as well as for cross-binding to heterologous Group 1 and Group 2 rHA proteins.…”