Heat-killed Listeria monocytogenes as an adjuvant converts established murine Th2-dominated immune responses into Th1-dominated responses.
We investigated the capacity of heat-killed Listeria monocytogenes (HKL), a potent stimulator of the innate immune system, as a vaccine adjuvant to modify both primary and secondary Ag-specific immune responses. Mice immunized with the Ag keyhole limpet hemocyanin (KLH) mixed with HKL generated a KLH-specific primary response characterized by production of Th1 cytokines and large quantities of KLH-specific IgG2a Ab. Moreover, administration of KLH with HKL as an adjuvant reversed established immune responses dominated by the production of Th2 cytokines and high levels of KLH-specific IgE and induced a Th1-type response with high levels of IFN-gamma and IgG2a and low levels of IgE and IL-4. Neutralization of IL-12 activity at the time of HKL administration blocked the enhancement of IFN-gamma and reduction of IL-4 production, indicating that IL-12, induced by HKL, was responsible for the adjuvant effects on cytokine production. These results suggest that HKL as an adjuvant during immunization can successfully bias the development of Ag-specific cytokine synthesis toward Th1 cytokine production even in the setting of an ongoing Th2-dominated response. Thus, HKL may be clinically effective in vaccine therapies for diseases such as allergy and asthma, which require the conversion of Th2-dominated immune responses into Th1-dominated responses.
Department of Pediatrics, Stanford University, CA 94305-5208, USA.
V P
VP
Yeung
R S
RS
Gieni
D T
DT
Umetsu
R H
RH
DeKruyff
D000276:Adjuvants, Immunologic; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001428:Bacterial Vaccines; D006358:Hot Temperature; D007111:Immunity, Cellular; D016056:Immunodominant Epitopes / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D016056:Immunodominant Epitopes