Multivariate analysis of cytokine responses identifies distinctive sensitivities to lipopolysaccharide in humans.

We describe methods to identify high and low responders in a whole-blood assay of lipopolysaccharide-stimulated cytokine responses. Two multivariate measures of the cytokine responses both captured high and low responses for each of the four individual cytokines that were assayed.

Host factors impacting the innate response in humans to the candidate adjuvants RC529 and monophosphoryl lipid A.

The aim of this study was to determine if certain genotypes might be associated with variable responses to the candidate vaccine adjuvants RC529 and monophosphoryl lipid A (MPL), as well as to bacterial LPS, a structurally similar control stimulus. In this study, the +896 TLR4 polymorphism and selected cytokine polymorphisms were genotyped, and together with the donor sex, these factors were used to model the in vitro cytokine responses to RC529, MPL, and LPS. We show evidence that each of the three stimuli engage human TLR4, that each gave higher responses in men than women, and that TLR4 expression levels in blood monocytes were higher in men than women.

Adjuvants recognized by toll-like receptors inhibit the induction of polarized type 2 T cell responses by natural attachment (G) protein of respiratory syncytial virus.

Immunization with native fusion (F) protein from respiratory syncytial virus (RSV) adsorbed to alum adjuvant generates greater than fourfold rises in serum neutralizing antibody titers in approximately 50% of seropositive humans. Using BALB/c mice we demonstrate herein that enhanced neutralization titers and accelerated clearance of virus from the lungs after challenge are possible if the attachment (G) glycoprotein is added to F protein-based vaccines. We further reveal for the first time that polarized type 2 T cell responses and immunopathology associated with G protein are inhibited by adjuvants recognized by toll-like receptors (TLR).