MPL Adjuvant Contains Competitive Antagonists of Human TLR4
FRONTIERS IN IMMUNOLOGY
Authors: Wang, Yi-Qi; Bazin-Lee, Helene; Evans, Jay T.; Casella, Carolyn R.; Mitchell, Thomas C.
Abstract
Monophosphoryl lipid A (MPL(R)) is the first non-alum vaccine adjuvant to achieve widespread clinical and market acceptance, a remarkable achievement given that it is manufactured from a Salmonella enterica endotoxin. To understand how MPL(R) successfully balanced the dual mandate of vaccine design-low reactogenicity with high efficacy-clinical- and research-grade MPL was evaluated in human and mouse cell systems. Stimulatory dose response curves revealed that most preparations of MPL are much more active in mouse than in human cell systems, and that the limited efficacy observed in human cells correlated with TLR4 inhibitory activity that resulted in a partial agonist profile. Further analysis of the major components of MPL(R) adjuvant prepared synthetically identified two structural variants that functioned as competitive antagonists of human TLR4. A partial agonist profile could be recapitulated and manipulated by spiking synthetic agonists with synthetic antagonists to achieve a broad dose range over which TLR4 stimulation could be constrained below a desired threshold. This report thus identifies mixed agonist-antagonist activity as an additional mechanism by which MPL(R) adjuvant is detoxified, relative to its parental LPS, to render it safe for use in prophylactic vaccines.
Efficacy of combinations of lactic acid and potassium sorbate against Listeria monocytogenes in chicken stored under modified atmospheres
FOOD MICROBIOLOGY
Authors: Gonzalez-Fandos, Elena; Martinez-Laorden, Alba; Perez-Arnedo, Iratxe
Abstract
The combined effect of lactic acid and potassium sorbate on the growth of L. monocytogenes on chicken legs packaged under modified atmospheres (MAP) and stored at 4 degrees C was evaluated. An extended lag phase and a lower maximum growth rate for psychrotrophs and mesophiles was found in those samples packaged in 20% CO2/80%N-2 and washed with different combinations of lactic acid and potassium sorbate compared to those non-treated with organic acids. Legs packaged in 20%C(O)2/80%N-2 and washed with 3.75% lactic acid 3.75% potassium sorbate showed a significant (p < 0.05) reduction in L. monocytogenes compared to untreated chicken legs packaged in MAP, which were approximately 2.63 log units lower in the first ones after 8 days of storage. Moreover, this treatment was the most effective in decreasing the maximum growth rate of L. monocytogenes. The chicken legs packaged in atmospheres containing 20%CO2/80%N-2, had an extended shelf life, but these atmospheres were not able to reduce L. monocytogenes, thus underlining the need for preventive measures so as to control this pathogen. The immersion of chicken legs in a solution containing 3.75% lactic acid 3.75% potassium sorbate can reduce L monocytogenes populations on fresh chicken packaged in a modified atmosphere.