Arias, MA

Carter, D

Coler, RN

Moutaftsi, M

Reed, SG

Shattock, RJ

Tregoning, JS

Van Roey, GA

Windish, HP

PLoS ONE

Successful vaccine development against HIV will likely require the induction of strong, long-lasting humoral and cellular
immune responses in both the systemic and mucosal compartments. Based on the known immunological linkage between
the upper-respiratory and urogenital tracts, we explored the potential of nasal adjuvants to boost immunization for the
induction of vaginal and systemic immune responses to gp140. Mice were immunized intranasally with HIV gp140 together
with micellar and emulsion formulations of a synthetic TLR4 agonist, Glucopyranosyl Lipid Adjuvant (GLA) and responses
were compared to R848, a TLR7/8 agonist, or chitosan, a non TLR adjuvant. GLA and chitosan but not R848 greatly
enhanced serum immunoglobulin levels when compared to antigen alone. Both GLA and chitosan induced high IgG and
IgA titers in nasal and vaginal lavage and feces. The high IgA and IgG titers in vaginal lavage were associated with high
numbers of gp140-specific antibody secreting cells in the genital tract. Whilst both GLA and chitosan induced T cell
responses to immunization, GLA induced a stronger Th17 response and chitosan induced a more Th2 skewed response. Our
results show that GLA is a highly potent intranasal adjuvant greatly enhancing humoral and cellular immune responses,
both systemically and mucosally

Spiral - Imperial College Digital Repository

Glucopyranosyl Lipid Adjuvant (GLA), a Synthetic TLR4 Agonist, Promotes Potent Systemic and Mucosal Responses to Intranasal Immunization with HIVgp140

http://spiral.imperial.ac.uk/bitstream/10044/1/29922/2/Glucopyranosyl%20Lipid%20Adjuvant%20%28GLA%29%2c%20a%20Synthetic%20TLR4%20agonist%2c%20promotes%20potent%20systemic%20and%20mucosal%20responses%20to%20intranasal%20immunization%20with%20HIVgp140..pdf

Glucopyranosyl Lipid Adjuvant (GLA), a Synthetic TLR4 Agonist, Promotes Potent Systemic and Mucosal Responses to Intranasal Immunization with HIVgp140

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Spiral - Imperial College Digital Repository