Adjuvant modulation of immune responses to tuberculosis subunit vaccines

Abstract

Mice were immunized with experimental subunit vaccines based on secreted antigens from Mycobacterium tuberculosis in a series of adjuvants, comprising incomplete Freund's adjuvant (IFA), dimethyl dioctadecyl ammoniumbromide (DDA), RIBI adjuvant, Quil-A saponin, and aluminum hydroxide. Immune responses induced by these vaccines were characterized by in vitro culture of primed cells, PCR analysis for cytokine mRNA, detection of specific immunoglobulin G isotypes induced, and monitoring of protective immunity to tuberculosis (TB). The study demonstrated marked differences in the immune responses induced by the different adjuvants and identified both IFA and DDA as efficient adjuvants for a TB subunit vaccine. Aluminum hydroxide, on the other hand, induced a Th2 response which increased the susceptibility of the animals to a subsequent TB challenge. DDA was further coadjuvanted with either the Th1-stimulating polymer poly(I-C) or the cytokines gamma interferon, interleukin 2 (IL-2), and IL-12. The addition of IL-12 was found to amplify a Th1 response in a dose-dependent manner and promoted a protective immune response against a virulent challenge. However, if the initial priming in the presence of IL-12 was followed by two booster injections of vaccine without IL-12, no improvement in long-term efficacy was found. This demonstrates the efficacy of DDA to promote an efficient immune response and suggests that IL-12 may accelerate this development, but not change the final outcome of a full vaccination regime. MATERIALS AND METHODS Mice. C57BL/6J female mice 8 to 12 weeks old were bred at Bomholtegaard breeding center, Ry, Denmark. Bacteria. M. tuberculosis H37Rv cells were grown at 37ЊC on Löwenstein-Jensen medium or in suspension in Sauton medium enriched with 0.5% sodium pyruvate and 0.5% glucose.

The effects of a novel adjuvant complex/Eimeria profilin vaccine on the intestinal host immune response against live E. acervulina challenge infection

“…Quil A by itself has been used as an adjuvant in many veterinary animal species, and defined saponins such as QS-21 are currently used in human clinical trials [36][37][38][39]. DDA provides a significant adjuvant effect when co-administered systemically or locally with antigen and stimulates predominantly Th1 cells with no reported toxic effects in humans [40][41][42][43][44][45][46]. In avians, DDA enhanced humoral and cell-mediated immune responses to a Newcastle disease virus vaccine and induced greater lymphocyte proliferation compared with complete Freund's adjuvant [22].…”

Embryo vaccination of chickens using a novel adjuvant formulation stimulates protective immunity against Eimeria maxima infection

“…In humans, Quil A-like saponin adjuvants, such as QS-21, are currently being used in clinical trials [30,31]. DDA stimulates predominantly Th1 cells when co-administered systemically or locally with antigen, and has no reported toxic effects in humans [32][33][34][35]. Chickens immunized with Eimeria merozoite antigens in combination with DDA displayed longer lasting immunity compared with a Corynebacterium parvum adjuvant [36].…”

Mineral Adjuvants∗∗The present chapter is an updated version of the chapter “Mineral Adjuvants,” published in Immunopotentiators in Modern Vaccines, p. 217–233. Ed. Virgil Schijns & Derek O'Hagan, Elsevier Science Publishers (2005).

“…A Th2-biased immune response is not likely to protect against diseases for which Th1 immunity and major histocompatibility complex (MHC) class Ierestricted CTLs are essential for protection, such as with, e.g., intracellular parasites or tuberculosis. 31 Another limitation lies in the fact that traditional aluminumand calcium-adsorbed vaccines are sensitive to freezing and therefore not lyophilizable. Assays for the detection of damages to vaccine formulations induced by freezing have been published.…”

“…However, as the proliferative responses were inhibited by anti-CD4 antibody, regardless of the adjuvant used, it indicated that the proliferating CD4 þ T cells from mice immunized using aluminum adjuvant were of the Th2 subset. Lindblad and coworkers 31 found a corresponding profile in C57BL/6J mice while performing reverse transcriptasepolymerase chain reaction for IL-4-and IL-10-specific messenger RNA (mRNA) in the regional draining lymph nodes at day 7 following vaccination with aluminumadjuvanted vaccine.…”