Unique Immunomodulating Properties of Dimethyl Dioctadecyl Ammonium Bromide (DDA) in Experimental Viral Vaccines

Katz, David A.; Lehrer, Shoshana; Galan, O.; Lachmi, Bat-El; Cohen, Sara; Inbar, Itzhak; Samina, I.; Peleg, Ben-Ami; Heller, Dan; Yadin, Hagai; Chai, Dafei; Freeman, Esther E.; Schupper, H.; Fuchs, Pinhas

doi:10.1007/978-1-4899-1382-1_16

Cited by 12 publications

(7 citation statements)

References 12 publications

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“…In this regard, the formation of a DDA depot ensuring the slow release of antigen has previously been hypothesized as a mechanism by which DDA may function (19). Experiments involving DDA performed by Katz and coworkers showed an antibody response of a longer duration compared to conventional adjuvants such as alum (22), demonstrating the induction of a persistent response with DDA. However, our studies with DDA alone (1) have never resulted in such striking levels of long-term memory as reported in the present study, and, therefore, in addition to the direct effect of DDA, there is undoubtedly an important effect of the mycobacterial lipids.…”

Section: Discussionmentioning

confidence: 99%

Cationic Liposomes Containing Mycobacterial Lipids: a New Powerful Th1 Adjuvant System

et al. 2005

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The immunostimulation provided by the mycobacterial cell wall has been exploited for many decades, e.g., in Freund's complete adjuvant. Recently, the underlying mechanism behind this adjuvant activity, including Toll receptor signaling, has begun to be unraveled, confirming the potential of mycobacterial constituents to act as adjuvants. In this study, the immunostimulatory properties of a Mycobacterium bovis BCG lipid extract were tested for their adjuvant activity. Administration of the lipids in dimethyl dioctadecyl ammonium bromide-based cationic liposomes induced a powerful Th1 response characterized by markedly elevated antigen-specific immunoglobulin G2a (IgG2a) isotype antibodies and substantial production of gamma interferon. The adjuvant formulation (designated mycosomes) elicited high levels of gamma interferon both in C57BL/6 as well as in Th2-prone BALB/c mice. Furthermore, the mycosomes induced immune responses to protein antigens from several sources including Mycobacterium tuberculosis, Chlamydia muridarum, and tetanus toxoid. In a tuberculosis challenge model, the mycosomes combined with the Ag85B-ESAT-6 fusion protein were demonstrated to have a unique ability to maintain sustained immunological memory at a level superior to live BCG.

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Section: Discussionmentioning

confidence: 99%

Cationic Liposomes Containing Mycobacterial Lipids: a New Powerful Th1 Adjuvant System

et al. 2005

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“…To observe the putative PGIA-promoting effect of the locus, we immunized another group of these congenic mice with PG in complete Freund’s adjuvant (FCA) instead of in DDA, which was used in earlier studies, 19 because PG injected with CFA induces slower PGIA progression than PG with DDA. 25 Indeed, using the PG-Freund’s adjuvant immunization protocol, we detected highly significant differences between Pgia21 -congenic and BALB/c wild-type littermates (Fig. 1B).…”

Section: Resultsmentioning

confidence: 85%

Congenic strains displaying similar clinical phenotype of arthritis represent different immunologic models of inflammation

et al. 2008

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Proteoglycan (PG)-induced arthritis (PGIA) is an autoimmune inflammatory disease controlled by multiple genes in the murine genome. BALB/c.DBA/2 congenic strains carrying four major PGIA chromosome loci were immunized, and positions of loci on chromosomes 3, 7, 8, and 19 (loci Pgia26, Pgia21, Pgia4, and Pgia12, respectively) were confirmed. Each congenic strain exhibited a different pattern of regulation of clinical and immunologic features of PGIA, and these features were significantly influenced by gender. Locus Pgia26 delayed PGIA onset in males and females, and the effect was associated with a lower rate of antigen-induced lymphocyte proliferation and lower production of IFN-γ, TNF-α, and IL-4. Pgia12 similarly delayed onset in males, but the effect was achieved via elevated proliferation of PG-specific lymphocytes and enhanced production of IFN-γ and IL-4. The effect of the Pgia21 locus was arthritis-suppressive in females but PGIA-permissive in congenic males. These opposite effects are attributed to 2-fold higher serum auto-antibody and IL-6 levels in males than in females. Our study supports the idea that each congenic strain represents a different immunologic subtype of PGIA, providing an explanation for the complex etiology and various clinical phenotypes of RA.

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“…60 DDA has also been shown to enhance antibody responses to various antigens. 61 In addition, regarding safety, DDA is less toxic than Freund's complete adjuvant, another commonly used form of adjuvant, so it is more suitable for vaccine preparation. 61 In this study, imiquimod was used as the basic component of the adjuvant, and DDA was used as the form of adjuvant to prepare a new adjuvant.…”

Section: ■ Discussionmentioning

confidence: 99%

“…61 In addition, regarding safety, DDA is less toxic than Freund's complete adjuvant, another commonly used form of adjuvant, so it is more suitable for vaccine preparation. 61 In this study, imiquimod was used as the basic component of the adjuvant, and DDA was used as the form of adjuvant to prepare a new adjuvant. After immunizing mice with the fusion protein DR2, it was found that it mainly induced Th1 cellular immune response.…”

Section: ■ Discussionmentioning

confidence: 99%

Long-Term Immunogenicity and In Vitro Prophylactic Protective Efficacy of M. tuberculosis Fusion Protein DR2 Combined with Liposomal Adjuvant DIMQ as a Boosting Vaccine for BCG

Mao

Wang

et al. 2023

ACS Infect. Dis.

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The resuscitation of dormant Mycobacterium tuberculosis is an important cause of adult tuberculosis (TB) transmission. According to the interaction mechanism between M. tuberculosis and the host, the latency antigen Rv0572c and region of difference 9 (RD9) antigen Rv3621c were selected in this study to prepare the fusion protein DR2. Stimulating clinically diagnosed active tuberculosis infections (i.e., TB patients), latent tuberculosis infections, and healthy controls confirmed that T lymphocytes could recognize DR2 protein in the peripheral blood of TB-infected individuals more than subcomponent protein. The DR2 protein was then emulsified in the liposome adjuvant dimethyl dioctadecyl ammonium bromide, and imiquimod (DIMQ) was administered to C57BL/6 mice immunized with Bacillus Calmette-Guérin (BCG) vaccine to evaluate their immunogenicity. Studies have shown that DR2/DIMQ, a booster vaccine for BCG primary immunization, can elicit robust CD4+ Th1 cell immune response and predominant IFN-γ+ CD4+ effector memory T cells (TEM) subsets. Furthermore, the serum antibody level and the expression of related cytokines increased significantly with the extension of immunization time, with IL2+, CD4+, or CD8+ central memory T cells (TCM) subsets predominant in the long term. This immunization strategy showed matched prophylactic protective efficacy by performing in vitro challenge experiment. This result provides robust evidence that the novel subunit vaccine prepared by fusion protein DR2 combined with liposomal adjuvant DIMQ is a promising TB vaccine candidate for further preclinical trials as a booster vaccine for BCG.

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Unique Immunomodulating Properties of Dimethyl Dioctadecyl Ammonium Bromide (DDA) in Experimental Viral Vaccines

Cited by 12 publications

References 12 publications

Cationic Liposomes Containing Mycobacterial Lipids: a New Powerful Th1 Adjuvant System

Cationic Liposomes Containing Mycobacterial Lipids: a New Powerful Th1 Adjuvant System

Congenic strains displaying similar clinical phenotype of arthritis represent different immunologic models of inflammation

Long-Term Immunogenicity and In Vitro Prophylactic Protective Efficacy of M. tuberculosis Fusion Protein DR2 Combined with Liposomal Adjuvant DIMQ as a Boosting Vaccine for BCG

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