An adjuvant formulation based on N-acetylglucosaminyl-N-acetylmuramyl-l-alanyl-d-isoglutamine with dimethyldioctadecylammonium chloride and zinc-l-proline complex as synergists

Grubhofer, N.

doi:10.1016/0165-2478(94)00188-w

Cited by 20 publications

(9 citation statements)

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“…Nevertheless, among the different conditions tested here, parenteral immunization with Gerbu adjuvant, used as a positive control, generated the highest immune response, in terms of immunoglobulin titers, IL-2 production by spleen cells and protective efficacy against an intratracheal M. tuberculosis challenge. Gerbu adjuvant has been developed as a more biotolerable alternative to complete Freund adjuvant [24] and is currently used for immunization of breeding animals but not of humans. By contrast, CpG oligonucleotides and MPLA have been developed for clinical applications [19]–[21].…”

Section: Discussionmentioning

confidence: 99%

“…Control mice were injected 100 µl subcutaneously (SC) in the back, three times at three weeks interval (on days 1, 21, 42), with 5 µg of purified recombinant Ag85A alone or emulsified in Gerbu adjuvant (GERBU Biochemicals, Germany). Gerbu adjuvant is a colloidal suspension composed of biodegradable cationic lipid nanoparticles (octa−/hexadecane) completed with a cell wall subunit of Lactobacillus bulgaricus [24]. Other control mice were instilled in the deep lungs with phosphate buffer solution (PBS) or CpG, MPLA or LTB alone.…”

Section: Methodsmentioning

confidence: 99%

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Mucosal and Systemic Immune Responses to Mycobacterium tuberculosis Antigen 85A following Its Co-Delivery with CpG, MPLA or LTB to the Lungs in Mice

et al. 2013

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Pulmonary vaccination is a promising route for immunization against tuberculosis because the lung is the natural site of infection with Mycobacterium tuberculosis. Yet, adjuvants with a suitable safety profile need to be found to enhance mucosal immunity to recombinant antigens. The aim of this study was to evaluate the immunogenicity, the safety and the protective efficacy of a subunit vaccine composed of the immunodominant mycolyl-transferase antigen 85A (Ag85A) and one of three powerful mucosal adjuvants: the oligodeoxynucleotide containing unmethylated cytosine-phosphate-guanine motifs (CpG), the monophosphoryl lipid A of Salmonella minnesota (MPLA) or the B subunit of heat-labile enterotoxin of Escherichia coli (LTB). BALB/c mice were vaccinated in the deep lungs. Our results showed that lung administration of these adjuvants could specifically induce different types of T cell immunity. Both CpG and MPLA induced a Th-1 type immune response with significant antigen-specific IFN-γ production by spleen mononuclear cells in vitro and a tendency of increased IFN-γ in the lungs. Moreover, MPLA triggered a Th-17 response reflected by high IL-17A levels in the spleen and lungs. By contrast, LTB promoted a Th-2 biased immune response, with a production of IL-5 but not IFN-γ by spleen mononuclear cells in vitro. CpG did not induce inflammation in the lungs while LTB and MPLA showed a transient inflammation including a neutrophil influx one day after pulmonary administration. Pulmonary vaccination with Ag85A without or with MPLA or LTB tended to decrease bacterial counts in the spleen and lungs following a virulent challenge with M. tuberculosis H37Rv. In conclusion, CpG and MPLA were found to be potential adjuvants for pulmonary vaccination against tuberculosis, providing Th-1 and Th-17 immune responses and a good safety profile.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Mucosal and Systemic Immune Responses to Mycobacterium tuberculosis Antigen 85A following Its Co-Delivery with CpG, MPLA or LTB to the Lungs in Mice

et al. 2013

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“…The significance of these findings with regard to heavy metal-induced proline accumulation in vivo has been discussed [50] . A synergistic immunological adjuvant formulation having bis[( l )prolinate-N,O]Zn complex as synergist has been patented which showed the pharmaceutical properties associated with the complex [51] .…”

Section: Bis[( L )Prolinate-no]zn Distribution Inmentioning

confidence: 99%

Bis[( l )prolinate-N,O]Zn: A water-soluble and recycle catalyst for various organic transformations

Poddar

Jain

Kidwai

2017

Journal of Advanced Research

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“…Microbiological sterility of the purified LH receptor and LH‐receptor implants was examined for bacterial and viral contamination by the microbiology laboratory of the NY Presbyterian Hospital, prior to and after the preparation of LH receptor implants. The LH‐R was emulsified with `Gerbu' [GMDP ( N ‐acetylglucosaminyl‐(β1–4) N ‐acetylmuramyl‐ L ‐alanyl‐ D ‐isoglutamine)] as the adjuvant (Grubhofer, N. 1995; Andronova et al 1996). The adjuvant was prepared from the subunit of mycobacterium cell wall (BioTech Corp. Inc., Poway, CA, USA).…”

Section: Methodsmentioning

confidence: 86%

Modulation of Ovarian Function in Female Dogs Immunized with Bovine Luteinizing Hormone Receptor

Saxena

Clavio

Singh

et al. 2002

Reprod Domestic Animals

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Adult female dogs were immunized with 0.5 mg bovine luteinizing hormone receptor (LH-R) encapsulated in a silastic subdermal implant and subsequently with four intramuscular booster injections of 0.1 mg LH-R each. Circulating LH-R antibody was detected in the sera 3 weeks post-implant. The appearance of LH-R antibody was associated with a decline in the serum progesterone concentrations to a range of 0-0.5 ng/ml until day 365 in the immunized dogs in comparison with a range of 5-10 ng in the control animals, suggesting a lack of ovulation and corpus luteum function in immunized dogs. The immunized dogs did not show signs of 'standing heat' and failed to ovulate when induced by LH-RH challenge. Serum oestradiol levels, however, remained in the range of 30-40 pg/ml in both the immunized and the control dogs. With the decline in the antibody titres, the hormonal profile and vaginal cytology returned to a fertile state and the dogs exhibited signs of 'standing heat', as well as vaginal bleeding. Dogs immunized with LH-R did not show any serious metabolic, local or systemic adverse effects. The hypothalamic--pituitary gonadal axis remained intact as indicated by little difference in pituitary LH levels between control and immunized animals, and by the release of LH by LH-RH challenge. These studies demonstrate that active immunization of female dogs with LH-R could immunomodulate ovarian function to cause a reversible state of infertility. It may be postulated that, due to extensive interspecies homology, a recombinant LH receptor-based immunocontraceptive vaccine may also be effective in other vertebrates.

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An adjuvant formulation based on N-acetylglucosaminyl-N-acetylmuramyl-l-alanyl-d-isoglutamine with dimethyldioctadecylammonium chloride and zinc-l-proline complex as synergists

Cited by 20 publications

References 10 publications

Mucosal and Systemic Immune Responses to Mycobacterium tuberculosis Antigen 85A following Its Co-Delivery with CpG, MPLA or LTB to the Lungs in Mice

Mucosal and Systemic Immune Responses to Mycobacterium tuberculosis Antigen 85A following Its Co-Delivery with CpG, MPLA or LTB to the Lungs in Mice

Bis[( l )prolinate-N,O]Zn: A water-soluble and recycle catalyst for various organic transformations

Modulation of Ovarian Function in Female Dogs Immunized with Bovine Luteinizing Hormone Receptor

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