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Glycophosphopeptical AM3 Food Supplement: A Potential Adjuvant in the Treatment and Vaccination of SARS-CoV-2.
Fernández-Lázaro, D, Fernandez-Lazaro, CI, Mielgo-Ayuso, J, Adams, DP, García Hernández, JL, González-Bernal, J, González-Gross, M
Frontiers in immunology. 2021;:698672
Abstract
The world is currently experiencing the coronavirus disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome-2 (SARS-CoV-2). Its global spread has resulted in millions of confirmed infections and deaths. While the global pandemic continues to grow, the availability of drugs to treat COVID-19 infections remains limited to supportive treatments. Moreover, the current speed of vaccination campaigns in many countries has been slow. Natural substrates with biological immunomodulatory activity, such as glucans, may represent an adjuvant therapeutic agent to treat SARS-CoV-2. AM3, a natural glycophosphopeptical, has previously been shown to effectively slow, with no side effects, the progression of infectious respiratory diseases by regulating effects on innate and adaptive immunity in experimental models. No clinical studies, however, exist on the use of AM3 in SARS-CoV-2 infected patients. This review aims to summarize the beneficial effects of AM3 on respiratory diseases, the inflammatory response, modulation of immune response, and attenuation of muscle. It will also discuss its potential effects as an immune system adjuvant for the treatment of COVID-19 infections and adjuvant for SARS-CoV-2 vaccination.
2.
AM3, a natural glycoconjugate, induces the functional maturation of human dendritic cells.
Martín-Vilchez, S, Molina-Jiménez, F, Alonso-Lebrero, JL, Sanz-Cameno, P, Rodríguez-Muñoz, Y, Benedicto, I, Roda-Navarro, P, Trapero, M, Aragoneses-Fenoll, L, González, S, et al
British journal of pharmacology. 2008;(3):698-708
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Abstract
BACKGROUND AND PURPOSE Dendritic cells (DCs) are dedicated antigen-presenting cells able to initiate specific immune responses and their maturation is critical for the induction of antigen-specific T-lymphocyte responses. Here, we have investigated the effects of Inmunoferon-active principle (AM3), the active agent of a commercial immunomodulatory drug, on human monocyte-derived DCs (MDDCs). EXPERIMENTAL APPROACH MDDCs derived from healthy and hepatitis C virus (HCV)-infected patients were stimulated with AM3. We analysed the expression of cell surface proteins by flow cytometry, that of cytokine production by ELISA, and the expression of chemokines and chemokine receptors by RNase protection assays. T-lymphocyte proliferation was assessed in mixed lymphocyte reactions, protein expression by western blot and luciferase-based reporter methods, and Toll-like receptor (TLR)-blocking antibodies were employed to analyse TLR activity. KEY RESULTS In MDDCs, AM3 induced or enhanced expression of CD54, CD83, CD86, HLA-DR, chemokines and chemokine receptors, interleukin (IL)-12p70 and IL-10. Furthermore, AM3 stimulated MDDCs to increase proliferation of allogenic T cells. AM3 triggered nuclear translocation of NF-kappaB and phosphorylation of p38 mitogen-activated protein kinase. AM3 promoted NF-kappaB activation in a TLR-4-dependent manner, and blocking TLR-4 activity attenuated the enhanced expression of CD80, CD83 and CD86 induced by AM3. AM3 enhanced the expression of maturation-associated markers in MDDCs from HCV-infected patients and increased the proliferation of T lymphocytes induced by these MDDCs. CONCLUSIONS AND IMPLICATIONS These results underline the effects of AM3 in promoting maturation of MDDCs and suggest that AM3 might be useful in regulating immune responses in pathophysiological situations requiring DC maturation.
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AM3 (Inmunoferón) as an adjuvant to hepatitis B vaccination in hemodialysis patients.
Pérez-García, R, Pérez-García, A, Verbeelen, D, Bernstein, ED, Villarrubia, VG, Alvarez-Mon, M
Kidney international. 2002;(5):1845-52
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Abstract
BACKGROUND Patients with end-stage renal disease (ESRD) undergoing hemodialysis have severe alterations in cell-mediated immunity (CMI) that increases their risk of contracting chronic hepatitis B virus (HBV) infection and decreases their protective responses to HBV vaccine. In an effort to improve the humoral response to an accelerated HBV vaccine protocol in these patients, the ability of an immunomodulator, AM3, to improve seroconversion was investigated. METHODS A total of 269 patients were enrolled in a multicenter trial. All patients received a DNA recombinant vaccine (40 microg HBsAg/dose/day) on days 0, 10, 21, and 90. AM3 or placebo (3 g/day) was given orally for 30 consecutive days beginning 15 days prior to the first vaccine dose. Anti-HBsAg titers were measured on days 120 and 270 after the beginning of the trial. RESULTS After one month, 207 patients could be evaluated and 132 patients after six months. The placebo and AM3-treated groups had comparable seroconversion and protective response rates one month after the final vaccine dose. The AM3 treatment group, but not the placebo group, maintained these protective titers up to six months after the final vaccine dose. At this time, the percentage of high responders (anti-HBsAg>100 IU/L) and mean anti-HBsAg titers in the AM3 group was significantly higher than in the placebo group. CONCLUSIONS AM3 is a safe and easily tolerated oral agent that potentiates long-term serological immunity to hepatitis B in hemodialysis patients after vaccination.