PyNTTTTGT prototype oligonucleotide IMT504 is a potent adjuvant for the recombinant Hepatitis B vaccine that enhances the Th1 response

Elı́as, Fernanda; Fló, Juan; Rodríguez, Juan Manuel; Nichilo, Analía De; López, Ricardo; Zorzopulos, Jorge; Nagle, Carlos A.; Lahoz, Mónica; Montaner, Alejandro D.

doi:10.1016/j.vaccine.2004.12.030

Cited by 25 publications

(21 citation statements)

References 23 publications

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“…Such examples include BioThrax (a licensed anthrax vaccine) in mice (ip or sc) and guinea pigs [104], hepatitis B virus vaccine (Engerix-B) in chimpanzees [105], poliovirus vaccine in mice [96], and Plasmodium falciparum Apical Membrane Antigen 1 vaccine in humans [106]. This also seems to be the case for non-CpG ODN, such as IMT504 (24-mer) with recombinant Hepatitis B surface antigen in monkeys [107]. When CpGs are used with aluminum-based vaccines, the immunostimulatory effect of CpG may depend on the relative association of CpG and antigen to the aluminum adjuvant [108].…”

Section: Oligonucleotidesmentioning

confidence: 99%

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Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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Section: Oligonucleotidesmentioning

confidence: 99%

“…For example, combining emulsion and a synthetic lipid A in Fluzone vaccine significantly and synergistically increased Th1 type response in mice [304]. Use of CpG often changes a Th2-type immune response of aluminum-based adjuvants to a Th1-type immune response [107,242,433].…”

Section: Adjuvant Combinationsmentioning

confidence: 99%

Selection of Adjuvants for Enhanced Vaccine Potency

Wang¹,

Singh²

2011

WJV

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“…Regarding this, extensive toxicity studies performed in our laboratory have demonstrated that IMT 504 is a very safe compound even at doses hundred times greater than the amount proposed for vaccines. In addition, we have reported promising pre-clinical results in two other vaccines adjuvanted with IMT504 [22,23].…”

Section: Discussionmentioning

confidence: 97%

“…In fact, IMT504 has been demonstrated to be immunostimulatory only in rats, monkeys and humans, with IMT504 being most active in humans [9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Therefore, we decided to perform a pilot study of rabies vaccination in human volunteers.…”

Section: Discussionmentioning

confidence: 99%

IMT504: A New and Potent Adjuvant for Rabies Vaccines Permitting Significant Dose Sparing

Montaner¹,

Nichilo²,

Rodríguez³

et al. 2012

WJV

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Background: Rabies virus infection causes encephalitis, which is almost always fatal. Vaccination can be extremely effective at preventing disease but is prohibitively costly. Vaccine formulations allowing dose-sparing and fewer inoculations with faster antibody response would be extremely desirable. IMT504, an immunostimulatory non-CpG oligodeoxynucleotide, is a highly potent vaccine adjuvant. Methods: Human and rat antibody measurements, and rat challenge studies were performed. Results: In rats, highly effective immune responses with IMT504 were observed even after diluting vaccine up to 1/625. In highly lethal, live intracerebral rabies challenge studies, protection occurred even with extremely dilute vaccine plus IMT504. In humans, antibody titers developed faster and were significantly higher with IMT504-adjuvanted diluted vaccine vs non-adjuvanted vaccine (full strength or diluted). All five administered IMT504-adjuvanted diluted vaccine reached protective antibodies (≥0.5 IU/ml) after the second injection. After the third injection, individuals receiving IMT504-adjuvanted diluted vaccine reached levels approximately 10 times higher than controls (M ± SEM: 31.0 ± 10.9 vs 3.40 ± 0.99 IU/ml). Conclusions: These data suggest that IMT504 may allow fewer inoculations, highly significant dose-sparing of vaccine, rapid antibody production and protection from rabies. Extensive clinical studies are necessary to confirm if the use of IMT504 will permit significantly greater access to highly effective life-saving rabies vaccines.

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“…Most of these effects indicate that IMT504 incubation empowers B cells for competent presentation of antigens to CD4+ T cells. In line with this, addition of IMT504 to different vaccines greatly increases their activity[371-373]. However, the strong secretion of IL-6 and IL-10 induced by IMT504 suggests that IMT504-activated B cells may also participate in regulation of the immune response.…”

Section: What Do We Know About the Mechanism Of Action Of Imt504 On Tmentioning

confidence: 96%

Immunomodulatory oligonucleotide IMT504: Effects on mesenchymal stem cells as a first-in-class immunoprotective/immunoregenerative therapy

Zorzopulos¹,

Opal²,

Hernando-Insúa³

et al. 2017

WJSC

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The immune responses of humans and animals to insults (i.e., infections, traumas, tumoral transformation and radiation) are based on an intricate network of cells and chemical messengers. Abnormally high inflammation immediately after insult or abnormally prolonged pro-inflammatory stimuli bringing about chronic inflammation can lead to life-threatening or severely debilitating diseases. Mesenchymal stem cell (MSC) transplant has proved to be an effective therapy in preclinical studies which evaluated a vast diversity of inflammatory conditions. MSCs lead to resolution of inflammation, preparation for regeneration and actual regeneration, and then ultimate return to normal baseline or homeostasis. However, in clinical trials of transplanted MSCs, the expectations of great medical benefit have not yet been fulfilled. As a practical alternative to MSC transplant, a synthetic drug with the capacity to boost endogenous MSC expansion and/or activation may also be effective. Regarding this, IMT504, the prototype of a major class of immunomodulatory oligonucleotides, induces in vivo expansion of MSCs, resulting in a marked improvement in preclinical models of neuropathic pain, osteoporosis, diabetes and sepsis. IMT504 is easily manufactured and has an excellent preclinical safety record. In the small number of patients studied thus far, IMT504 has been well-tolerated, even at very high dosage. Further clinical investigation is necessary to demonstrate the utility of IMT504 for resolution of inflammation and regeneration in a broad array of human diseases that would likely benefit from an immunoprotective/immunoregenerative therapy.

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PyNTTTTGT prototype oligonucleotide IMT504 is a potent adjuvant for the recombinant Hepatitis B vaccine that enhances the Th1 response

Cited by 25 publications

References 23 publications

Selection of Adjuvants for Enhanced Vaccine Potency

Selection of Adjuvants for Enhanced Vaccine Potency

IMT504: A New and Potent Adjuvant for Rabies Vaccines Permitting Significant Dose Sparing

Immunomodulatory oligonucleotide IMT504: Effects on mesenchymal stem cells as a first-in-class immunoprotective/immunoregenerative therapy

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