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Since the beginning of the 2021 year, all the main six vaccines against COVID-19 have been used in mass vaccination companies around the world. Virus neutralization and epidemiological efficacy drop obtained for several vaccines against the B.1.1.7, B.1.351 P.1, and B.1.617 genotypes are of concern. There is a growing number of reports on mutations in receptor-binding domain (RBD) increasing the transmissibility of the virus and escaping the neutralizing effect of antibodies. The Sputnik V vaccine is currently approved for use in more than 66 countries but its activity against variants of concern (VOC) is not extensively studied yet. Virus-neutralizing activity (VNA) of sera obtained from people vaccinated with Sputnik V in relation to internationally relevant genetic lineages B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3 and Moscow endemic variants B.1.1.141 (T385I) and B.1.1.317 (S477N, A522S) with mutations in the RBD domain has been assessed. The data obtained indicate no significant differences in VNA against B.1.1.7, B.1.617.3 and local genetic lineages B.1.1.141 (T385I), B.1.1.317 (S477N, A522S) with RBD mutations. For the B.1.351, P.1, and B.1.617.2 statistically significant 3.1-, 2.8-, and 2.5-fold, respectively, VNA reduction was observed. Notably, this decrease is lower than that reported in publications for other vaccines. However, a direct comparative study is necessary for a conclusion. Thus, sera from “Sputnik V”-vaccinated retain neutralizing activity against VOC B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3 as well as local genetic lineages B.1.1.141 and B.1.1.317 circulating in Moscow.
Vladimir Gushchin; Inna Dolzhikova; Alexey Shchetinin; Alina Odintsova; Andrei Siniavin; Maria Nikiforova; Andrei Pochtovyi; Elena Shidlovskaya; Nadezhda Kuznetsova; Olga Burgasova; Liudmila Kolobukhina; Anna Iliukhina; Anna Kovyrshina; Andrey Botikov; Aleksandra Kuzina; Daria Grousova; Amir Tukhvatulin; Dmitry Shcheblyakov; Olga Zubkova; Oksana Karpova; Olga Voronina; Natalia Ryzhova; Ekaterina Aksenova; Marina Kunda; Dmitry Lioznov; Daria Danilenko; Andrey Komissarov; Artem Tkachuck; Denis Logunov; Alexander Gintsburg. Neutralizing Activity of Sera from Sputnik V-Vaccinated People against Variants of Concern (VOC: B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3) and Moscow Endemic SARS-CoV-2 Variants. Vaccines 2021, 9, 779 .
AMA StyleVladimir Gushchin, Inna Dolzhikova, Alexey Shchetinin, Alina Odintsova, Andrei Siniavin, Maria Nikiforova, Andrei Pochtovyi, Elena Shidlovskaya, Nadezhda Kuznetsova, Olga Burgasova, Liudmila Kolobukhina, Anna Iliukhina, Anna Kovyrshina, Andrey Botikov, Aleksandra Kuzina, Daria Grousova, Amir Tukhvatulin, Dmitry Shcheblyakov, Olga Zubkova, Oksana Karpova, Olga Voronina, Natalia Ryzhova, Ekaterina Aksenova, Marina Kunda, Dmitry Lioznov, Daria Danilenko, Andrey Komissarov, Artem Tkachuck, Denis Logunov, Alexander Gintsburg. Neutralizing Activity of Sera from Sputnik V-Vaccinated People against Variants of Concern (VOC: B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3) and Moscow Endemic SARS-CoV-2 Variants. Vaccines. 2021; 9 (7):779.
Chicago/Turabian StyleVladimir Gushchin; Inna Dolzhikova; Alexey Shchetinin; Alina Odintsova; Andrei Siniavin; Maria Nikiforova; Andrei Pochtovyi; Elena Shidlovskaya; Nadezhda Kuznetsova; Olga Burgasova; Liudmila Kolobukhina; Anna Iliukhina; Anna Kovyrshina; Andrey Botikov; Aleksandra Kuzina; Daria Grousova; Amir Tukhvatulin; Dmitry Shcheblyakov; Olga Zubkova; Oksana Karpova; Olga Voronina; Natalia Ryzhova; Ekaterina Aksenova; Marina Kunda; Dmitry Lioznov; Daria Danilenko; Andrey Komissarov; Artem Tkachuck; Denis Logunov; Alexander Gintsburg. 2021. "Neutralizing Activity of Sera from Sputnik V-Vaccinated People against Variants of Concern (VOC: B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.617.3) and Moscow Endemic SARS-CoV-2 Variants." Vaccines 9, no. 7: 779.
The Lassa virus one of the main etiological agent of hemorrhagic fevers in the world: according to WHO estimates, it affects 100,000 to 300,000 people annually, which results in up to 10,000 deaths [1]. Although expansion of Lassa fever caused by this pathogen is mostly limited to the West African countries: Sierra Leone, Liberia, Guinea and Nigeria, imported cases have been historically documented in Europe, the United States of America (USA), Canada, Japan, and Israel [2]. In 2017, WHO included the Lassa virus in the list of priority pathogens in need of accelerated research, development of vaccines, therapeutic agents and diagnostic tools regarding infections they cause [3]. This review describes main technological platforms used for the development of vaccines for the prevention of Lassa fever.
O. D. Popova; O. V. Zubkova; T. A. Ozharovskaia; D. I. Zrelkin; D. V. Voronina; I. V. Dolzhikova; D. V. Shcheblyakov; B. S. Naroditsky; D. Yu. Logunov; A. L. Gintsburg. Review of candidate vaccines for the prevention of Lassa fever. Problems of Virology 2021, 66, 91 -102.
AMA StyleO. D. Popova, O. V. Zubkova, T. A. Ozharovskaia, D. I. Zrelkin, D. V. Voronina, I. V. Dolzhikova, D. V. Shcheblyakov, B. S. Naroditsky, D. Yu. Logunov, A. L. Gintsburg. Review of candidate vaccines for the prevention of Lassa fever. Problems of Virology. 2021; 66 (2):91-102.
Chicago/Turabian StyleO. D. Popova; O. V. Zubkova; T. A. Ozharovskaia; D. I. Zrelkin; D. V. Voronina; I. V. Dolzhikova; D. V. Shcheblyakov; B. S. Naroditsky; D. Yu. Logunov; A. L. Gintsburg. 2021. "Review of candidate vaccines for the prevention of Lassa fever." Problems of Virology 66, no. 2: 91-102.
Background and objectives COVID‐19 convalescent plasma is an experimental treatment against SARS‐CoV‐2. The aim of this study is to assess the impact of different pathogen reduction methods on the levels and virus neutralizing activity of the specific antibodies against SARS‐CoV2 in convalescent plasma. Materials and methods A total of 140 plasma doses collected by plasmapheresis from COVID‐19 convalescent donors were subjected to pathogen reduction by three methods: methylene blue (M)/visible light, riboflavin (R)/UVB and amotosalen (A)/UVA. To conduct a paired comparison, individual plasma doses were divided into 2 samples that were subjected to one of these methods. The titres of SARS‐CoV2 neutralizing antibodies (NtAbs) and levels of specific immunoglobulins to RBD, S‐ and N‐proteins of SARS‐CoV‐2 were measured before and after pathogen reduction. Results The methods reduced NtAbs titres differently: among units with the initial titre 80 or above, 81% of units remained unchanged and 19% decreased by one step after methylene blue; 60% were unchanged and 40% decreased by one step after amotosalen; after riboflavin 43% were unchanged and 50% (7%, respectively) had a one‐step (two‐step, respectively) decrease. Paired two‐sample comparisons (M vs. A, M vs. R and A vs. R) revealed that the largest statistically significant decrease in quantity and activity of the specific antibodies resulted from the riboflavin treatment. Conclusion Pathogen reduction with methylene blue or with amotosalen provides the greater likelihood of preserving the immunological properties of the COVID‐19 convalescent plasma compared to riboflavin.
Alexander I. Kostin; Maria N. Lundgren; Andrey Y. Bulanov; Elena A. Ladygina; Karina S. Chirkova; Alexander L. Gintsburg; Denis Y. Logunov; Inna V. Dolzhikova; Dmitry V. Shcheblyakov; Natalia V. Borovkova; Mikhail A. Godkov; Alexey I. Bazhenov; Valeriy V. Shustov; Alina S. Bogdanova; Alina R. Kamalova; Vladimir V. Ganchin; Eugene A. Dombrovskiy; Stanislav E. Volkov; Nataliya E. Drozdova; Sergey S. Petrikov. Impact of pathogen reduction methods on immunological properties of the COVID‐19 convalescent plasma. Vox Sanguinis 2021, 1 .
AMA StyleAlexander I. Kostin, Maria N. Lundgren, Andrey Y. Bulanov, Elena A. Ladygina, Karina S. Chirkova, Alexander L. Gintsburg, Denis Y. Logunov, Inna V. Dolzhikova, Dmitry V. Shcheblyakov, Natalia V. Borovkova, Mikhail A. Godkov, Alexey I. Bazhenov, Valeriy V. Shustov, Alina S. Bogdanova, Alina R. Kamalova, Vladimir V. Ganchin, Eugene A. Dombrovskiy, Stanislav E. Volkov, Nataliya E. Drozdova, Sergey S. Petrikov. Impact of pathogen reduction methods on immunological properties of the COVID‐19 convalescent plasma. Vox Sanguinis. 2021; ():1.
Chicago/Turabian StyleAlexander I. Kostin; Maria N. Lundgren; Andrey Y. Bulanov; Elena A. Ladygina; Karina S. Chirkova; Alexander L. Gintsburg; Denis Y. Logunov; Inna V. Dolzhikova; Dmitry V. Shcheblyakov; Natalia V. Borovkova; Mikhail A. Godkov; Alexey I. Bazhenov; Valeriy V. Shustov; Alina S. Bogdanova; Alina R. Kamalova; Vladimir V. Ganchin; Eugene A. Dombrovskiy; Stanislav E. Volkov; Nataliya E. Drozdova; Sergey S. Petrikov. 2021. "Impact of pathogen reduction methods on immunological properties of the COVID‐19 convalescent plasma." Vox Sanguinis , no. : 1.
Background and ObjectivesCOVID-19 convalescent plasma has become an experimental treatment option against SARS-CoV2. The aim of this study is to assess the impact of different pathogen reduction methods on the immunological properties of COVID-19 convalescent plasma.Materials and MethodsA total of 140 plasma doses collected by plasmapheresis from COVID-19 convalescent donors were subjected to pathogen reduction by three different methods: methylene blue (M), riboflavin (R), and amotosalen (A). To conduct a paired two-sample comparison, individual plasma doses were divided into 2 samples that were subjected to one of these methods. The titres of SARS-CoV2 neutralizing antibodies (NtAbs) and levels of specific immunoglobulins to RBD, S- and N-proteins of SARS-CoV-2 were measured before and after pathogen reduction.ResultsAll methods reduced NtAbs titres significantly but not equally: among units with the initial titre 80 or above, 81% of units had unchanged titres while 19% decreased by 1 step after methylene blue; 60% were unchanged and 40% decreased by 1 step after amotosalen; whereas after riboflavin 43% were unchanged, 50% had a one-step decrease and 7% a two-step decrease. Paired two-sample comparisons (M vs A, M vs R and A vs R) revealed that the most prominent and statistically significant decrease in all studied parameters (except anti-RBD) resulted from the riboflavin treatment.ConclusionPathogen reduction with methylene blue and amotosalen provides the greater likelihood of preserving the immunological properties of the COVID-19 convalescent plasma compared to riboflavin.
Alexander I. Kostin; Maria N. Lundgren; Andrey Y. Bulanov; Elena A. Ladygina; Karina S. Chirkova; Alexander L. Gintsburg; Denis Y. Logunov; Inna V. Dolzhikova; Dmitry V. Shcheblyakov; Natalia V. Borovkova; Mikhail A. Godkov; Alexey I. Bazhenov; Valeriy V. Shustov; Alina S. Bogdanova; Alina R. Kamalova; Vladimir V. Ganchin; Eugene A. Dombrovskiy; Stanislav E. Volkov; Nataliya E. Drozdova; Sergey S. Petrikov. Impact of pathogen reduction methods on immunological properties of the COVID-19 convalescent plasma. 2020, 1 .
AMA StyleAlexander I. Kostin, Maria N. Lundgren, Andrey Y. Bulanov, Elena A. Ladygina, Karina S. Chirkova, Alexander L. Gintsburg, Denis Y. Logunov, Inna V. Dolzhikova, Dmitry V. Shcheblyakov, Natalia V. Borovkova, Mikhail A. Godkov, Alexey I. Bazhenov, Valeriy V. Shustov, Alina S. Bogdanova, Alina R. Kamalova, Vladimir V. Ganchin, Eugene A. Dombrovskiy, Stanislav E. Volkov, Nataliya E. Drozdova, Sergey S. Petrikov. Impact of pathogen reduction methods on immunological properties of the COVID-19 convalescent plasma. . 2020; ():1.
Chicago/Turabian StyleAlexander I. Kostin; Maria N. Lundgren; Andrey Y. Bulanov; Elena A. Ladygina; Karina S. Chirkova; Alexander L. Gintsburg; Denis Y. Logunov; Inna V. Dolzhikova; Dmitry V. Shcheblyakov; Natalia V. Borovkova; Mikhail A. Godkov; Alexey I. Bazhenov; Valeriy V. Shustov; Alina S. Bogdanova; Alina R. Kamalova; Vladimir V. Ganchin; Eugene A. Dombrovskiy; Stanislav E. Volkov; Nataliya E. Drozdova; Sergey S. Petrikov. 2020. "Impact of pathogen reduction methods on immunological properties of the COVID-19 convalescent plasma." , no. : 1.
Along with their excellent safety profiles, subunit vaccines are typically characterized by much weaker immunogenicity and protection efficacy compared to whole-pathogen vaccines. Here, we present an approach aimed at bridging this disadvantage that is based on synergistic collaboration between pattern-recognition receptors (PRRs) belonging to different families. We prepared a model subunit vaccine formulation using an influenza hemagglutinin antigen incorporated into poly-(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles adjuvanted with monophosphoryl lipid A (TLR4 agonist) and muramyl dipeptide (NOD2 agonist). The efficacy studies were conducted in comparison to control vaccine formulations containing individual PRR agonists. We show that the complex adjuvant based on TLR4 and NOD2 agonists potentiates proinflammatory cell responses (measured by activity of transcription factors and cytokine production both in vitro and in vivo) and enhances the phagocytosis of vaccine particles up to comparable levels of influenza virus uptake. Finally, mice immunized with vaccine nanoparticles containing both PRR agonists exhibited enhanced humoral (IgG, hemagglutination-inhibition antibody titers) and cellular (percentage of proliferating CD4+ T-cells, production of IFNɣ) immunity, leading to increased resistance to lethal influenza challenge. These results support the idea that complex adjuvants stimulating different PRRs may present a better alternative to individual PAMP-based adjuvants and could further narrow the gap between the efficacy of subunit versus whole-pathogen vaccines.
Amir Tukhvatulin; Alina Dzharullaeva; Alina Erokhova; Anastasia Zemskaya; Maxim Balyasin; Tatiana Ozharovskaia; Olga Zubkova; Natalia Shevlyagina; Vladimir Zhukhovitsky; Irina Fedyakina; Ivan Pruss; Dmitry Shcheblyakov; Boris Naroditsky; Denis Logunov; Alexander Gintsburg. Adjuvantation of an Influenza Hemagglutinin Antigen with TLR4 and NOD2 Agonists Encapsulated in Poly(D,L-Lactide-Co-Glycolide) Nanoparticles Enhances Immunogenicity and Protection against Lethal Influenza Virus Infection in Mice. Vaccines 2020, 8, 519 .
AMA StyleAmir Tukhvatulin, Alina Dzharullaeva, Alina Erokhova, Anastasia Zemskaya, Maxim Balyasin, Tatiana Ozharovskaia, Olga Zubkova, Natalia Shevlyagina, Vladimir Zhukhovitsky, Irina Fedyakina, Ivan Pruss, Dmitry Shcheblyakov, Boris Naroditsky, Denis Logunov, Alexander Gintsburg. Adjuvantation of an Influenza Hemagglutinin Antigen with TLR4 and NOD2 Agonists Encapsulated in Poly(D,L-Lactide-Co-Glycolide) Nanoparticles Enhances Immunogenicity and Protection against Lethal Influenza Virus Infection in Mice. Vaccines. 2020; 8 (3):519.
Chicago/Turabian StyleAmir Tukhvatulin; Alina Dzharullaeva; Alina Erokhova; Anastasia Zemskaya; Maxim Balyasin; Tatiana Ozharovskaia; Olga Zubkova; Natalia Shevlyagina; Vladimir Zhukhovitsky; Irina Fedyakina; Ivan Pruss; Dmitry Shcheblyakov; Boris Naroditsky; Denis Logunov; Alexander Gintsburg. 2020. "Adjuvantation of an Influenza Hemagglutinin Antigen with TLR4 and NOD2 Agonists Encapsulated in Poly(D,L-Lactide-Co-Glycolide) Nanoparticles Enhances Immunogenicity and Protection against Lethal Influenza Virus Infection in Mice." Vaccines 8, no. 3: 519.
Purpose: Pathogens consist of a wide variety of evolutionarily conserved molecular structures that are recognized by pattern recognition receptors (PRRs) of innate immunity. Reasonably assuming that no single PRR is ever likely to be the sole trigger of the immune response during infection, a great deal remains unknown about collaborative mechanisms and consequential crosstalk effects between multiple PRRs belonging to different families. Here, we aimed to investigate inflammatory response to combined stimulation of cytosolic nucleotide-binding oligomerization domain (NOD) receptors: NOD1, NOD2 and membrane-bound C-type lectin receptors (CLRs): Mincle and Dectin-1 in comparison to individual stimulation both in vitro and in vivo. Materials and Methods: For in vitro studies, we used human monocytic THP-1 cells endogenously expressing NOD1,2, as well as Mincle and Dectin-1 receptors. Using reporter gene and immunoassay approaches, we measured activity of key proinflammatory transcription factors (NF-κB and AP-1) and cytokine production after addition of specific PRR agonists or their pairwise combinations. In vivo NF-κB activity (bioluminescent detection in NF-κB-Luc transgenic mice), as well as cytokine levels in mouse blood serum, was measured 3 hours after intramuscular injection of PRR agonists. Results: We detected that combined stimulation of NOD1/2 and C-type lectin receptors (Dectin-1, Mincle) strongly potentiates NF-κB and AP-1 transcription factor activity in human monocytic THP-1 cells, as well as resulting in enhanced levels of IL-8 cytokine production. We demonstrated that RIP2- and Syk-dependent signaling pathways downstream of NOD1/2 and Dectin-1/Mincle, respectively, are essential for the potentiated proinflammatory cell response. Lastly, we confirmed that synergy between NOD and C-type lectin receptors resulting in potentiated levels of NF-κB activation and cytokine (IL-6, KC) production also occurs in vivo. Conclusion: These findings originally indicate cooperation between NODs and CLRs, leading to potentiated levels of proinflammatory immune response both in vitro and in vivo.
Amir I Tukhvatulin; Alina S Dzharullaeva; Alina S Erokhova; Dmitry V Scheblyakov; Boris S Naroditsky; Alexander L Gintsburg; Denis Y Logunov. NOD1/2 and the C-Type Lectin Receptors Dectin-1 and Mincle Synergistically Enhance Proinflammatory Reactions Both In Vitro and In Vivo. Journal of Inflammation Research 2020, ume 13, 357 -368.
AMA StyleAmir I Tukhvatulin, Alina S Dzharullaeva, Alina S Erokhova, Dmitry V Scheblyakov, Boris S Naroditsky, Alexander L Gintsburg, Denis Y Logunov. NOD1/2 and the C-Type Lectin Receptors Dectin-1 and Mincle Synergistically Enhance Proinflammatory Reactions Both In Vitro and In Vivo. Journal of Inflammation Research. 2020; ume 13 ():357-368.
Chicago/Turabian StyleAmir I Tukhvatulin; Alina S Dzharullaeva; Alina S Erokhova; Dmitry V Scheblyakov; Boris S Naroditsky; Alexander L Gintsburg; Denis Y Logunov. 2020. "NOD1/2 and the C-Type Lectin Receptors Dectin-1 and Mincle Synergistically Enhance Proinflammatory Reactions Both In Vitro and In Vivo." Journal of Inflammation Research ume 13, no. : 357-368.
The bacterium Clostridium botulinum is the causative agent of botulism—a severe intoxication caused by botulinum neurotoxin (BoNT) and characterized by damage to the nervous system. In an effort to develop novel C. botulinum immunotherapeutics, camelid single-domain antibodies (sdAbs, VHHs, or nanobodies) could be used due to their unique structure and characteristics. In this study, VHHs were produced using phage display technology. A total of 15 different monoclonal VHHs were selected based on their comlementarity-determining region 3 (CDR3) sequences. Different toxin lethal dose (LD50) challenges with each selected phage clone were conducted in vivo to check their neutralizing potency. We demonstrated that modification of neutralizing VHHs with a human immunoglobulin G (IgG)1 Fc (fragment crystallizable) fragment (fusionbody, VHH-Fc) significantly increased the circulation time in the blood (up to 14 days). At the same time, VHH-Fc showed the protective activity 1000 times higher than monomeric form when challenged with 5 LD50. Moreover, VHH-Fcs remained protective even 14 days after antibody administration. These results indicate that this VHH-Fc could be used as an effective long term antitoxin protection against botulinum type A.
Svetlana A. Godakova; Anatoly N. Noskov; Irina D. Vinogradova; Galina A. Ugriumova; Andrey I. Solovyev; Ilias B. Esmagambetov; Amir I. Tukhvatulin; Denis Y. Logunov; Boris S. Naroditsky; Dmitry V. Shcheblyakov; Aleksandr L. Gintsburg. Camelid VHHs Fused to Human Fc Fragments Provide Long Term Protection Against Botulinum Neurotoxin A in Mice. Toxins 2019, 11, 464 .
AMA StyleSvetlana A. Godakova, Anatoly N. Noskov, Irina D. Vinogradova, Galina A. Ugriumova, Andrey I. Solovyev, Ilias B. Esmagambetov, Amir I. Tukhvatulin, Denis Y. Logunov, Boris S. Naroditsky, Dmitry V. Shcheblyakov, Aleksandr L. Gintsburg. Camelid VHHs Fused to Human Fc Fragments Provide Long Term Protection Against Botulinum Neurotoxin A in Mice. Toxins. 2019; 11 (8):464.
Chicago/Turabian StyleSvetlana A. Godakova; Anatoly N. Noskov; Irina D. Vinogradova; Galina A. Ugriumova; Andrey I. Solovyev; Ilias B. Esmagambetov; Amir I. Tukhvatulin; Denis Y. Logunov; Boris S. Naroditsky; Dmitry V. Shcheblyakov; Aleksandr L. Gintsburg. 2019. "Camelid VHHs Fused to Human Fc Fragments Provide Long Term Protection Against Botulinum Neurotoxin A in Mice." Toxins 11, no. 8: 464.
Induction of a robust and long-lived mucosal immune response during vaccination is critical to achieve protection against numerous pathogens. However, traditional injected vaccines are generally poor inducers of mucosal immunity. One of the effective strategies to improve vaccine efficacy is incorporation of adjuvant molecules that enhance and polarize adaptive immune reactions. Effects of Syk-coupled lectin receptor agonists as adjuvants to induce mucosal immune reactions during parenteral immunization are not fully studied. We now report that the agonists trehalose-6,6-dibehenate (TDB), curdlan, and furfurman, which stimulate Dectin-1, Dectin-2, and Mincle, respectively, activate transcription factors (NF-κB, NFAT, and AP-1) to various extents in murine RAW 264.7 macrophages, even though similar pathways are activated. The agonists also elicit differential expression of maturation markers in bone marrow-derived dendritic cells, as well as differential cytokine secretion from these cells and from splenic mononuclear cells. In vivo assays also show that agonists of Dectin-1 and Dectin-2, but not Mincle, induce heavy IgA secretion in intestinal mucosa even when delivered parenterally. Strikingly, this effect appears to be formulation-independent. Collectively, the data suggest that adjuvants based on Dectin-1 and Dectin-2 agonists may significantly improve the efficacy of parenteral vaccines by inducing robust local immune reactions in intestinal mucosa.
Alina S. Dzharullaeva; Amir I. Tukhvatulin; Alina S. Erokhova; Alina S. Bandelyuk; Nikita B. Polyakov; Andrey I. Solovyev; Natalia A. Nikitenko; Dmitry V. Shcheblyakov; Boris Naroditsky; Denis Y. Logunov; Alexander L. Gintsburg. Stimulation of Dectin-1 and Dectin-2 during Parenteral Immunization, but Not Mincle, Induces Secretory IgA in Intestinal Mucosa. Journal of Immunology Research 2018, 2018, 1 -13.
AMA StyleAlina S. Dzharullaeva, Amir I. Tukhvatulin, Alina S. Erokhova, Alina S. Bandelyuk, Nikita B. Polyakov, Andrey I. Solovyev, Natalia A. Nikitenko, Dmitry V. Shcheblyakov, Boris Naroditsky, Denis Y. Logunov, Alexander L. Gintsburg. Stimulation of Dectin-1 and Dectin-2 during Parenteral Immunization, but Not Mincle, Induces Secretory IgA in Intestinal Mucosa. Journal of Immunology Research. 2018; 2018 ():1-13.
Chicago/Turabian StyleAlina S. Dzharullaeva; Amir I. Tukhvatulin; Alina S. Erokhova; Alina S. Bandelyuk; Nikita B. Polyakov; Andrey I. Solovyev; Natalia A. Nikitenko; Dmitry V. Shcheblyakov; Boris Naroditsky; Denis Y. Logunov; Alexander L. Gintsburg. 2018. "Stimulation of Dectin-1 and Dectin-2 during Parenteral Immunization, but Not Mincle, Induces Secretory IgA in Intestinal Mucosa." Journal of Immunology Research 2018, no. : 1-13.
Previously we demonstrated that the resection of primary 4T1 tumors only slightly prolongs mouse survival, but importantly, creates a "window of opportunity" with attenuated suppressor cell and increased activated T cell populations. This suggests that additional activation of the immune system by immunostimulatory agents during this period may enhance anti-tumor immunity and potentially eradicate micro-metastatic disease in this stringent model. We hypothesized that the immunostimulator Immunomax®, which is comprised of a plant-derived polysaccharide, is non-toxic in humans and stimulates immune defense during the infectious diseases treatment, may have also anti-tumor activity and be beneficial in the adjuvant setting when endogenous anti-tumor responses are present and during the "window of opportunity" in post-resection metastatic breast cancer model. Here we provide the initial report that Immunomax® demonstrates the capacity to eliminate micro-metastatic disease in the post-resection, 4T1 mouse model of breast cancer. The efficacy of Immunomax® was evaluated by analyzing survival rate and the number of spontaneous clonogenic tumor cells in the lung homogenates of mice. The frequencies of activated NK, CD4(+) and CD8(+) cells as well as myeloid-derived suppressor cells and Treg cells were evaluated using flow cytometry. Highly purified mouse and human dendritic and NK cells were sorted and the effect of Immunomax® on activation status of these cells was assessed by flow cytometry. The property of Immunomax® as TLR-4 agonist was determined by NF-κB/SEAP reporter gene assay, WB, RT-PCR. Immunomax® injections significantly prolonged overall survival and cured 31% of mice. This immunostimulator activates DCs via the TLR-4, which in turn stimulates tumoricidal NK cells and in vitro, completely inhibits growth of 4T1 cells. Incubation of PBMC from healthy donors with Immunomax® activates NK cells via activation of plasmacytoid DC leading significantly higher efficacy in killing of human NK-target cells K562 compared with non-treated cells. This is the first demonstration that Immunomax® is a TLR-4 agonist and the first report of a documented role for this pharmaceutical grade immunostimulator in augmenting anti-tumor activity, suggesting that incorporation of Immunomax® into developing breast cancer therapeutic strategies may be beneficial and with less potential toxicity than checkpoint inhibitors.
Anahit Ghochikyan; Alexey Pichugin; Alexander Bagaev; Arpine Davtyan; Armine Hovakimyan; Amir Tukhvatulin; Hayk Davtyan; Dmitry Shcheblyakov; Denis Logunov; Marina Chulkina; Anastasia Savilova; Dmitry Trofimov; Edward L Nelson; Michael G Agadjanyan; Ravshan I Ataullakhanov. Targeting TLR-4 with a novel pharmaceutical grade plant derived agonist, Immunomax®, as a therapeutic strategy for metastatic breast cancer. Journal of Translational Medicine 2014, 12, 322 .
AMA StyleAnahit Ghochikyan, Alexey Pichugin, Alexander Bagaev, Arpine Davtyan, Armine Hovakimyan, Amir Tukhvatulin, Hayk Davtyan, Dmitry Shcheblyakov, Denis Logunov, Marina Chulkina, Anastasia Savilova, Dmitry Trofimov, Edward L Nelson, Michael G Agadjanyan, Ravshan I Ataullakhanov. Targeting TLR-4 with a novel pharmaceutical grade plant derived agonist, Immunomax®, as a therapeutic strategy for metastatic breast cancer. Journal of Translational Medicine. 2014; 12 (1):322.
Chicago/Turabian StyleAnahit Ghochikyan; Alexey Pichugin; Alexander Bagaev; Arpine Davtyan; Armine Hovakimyan; Amir Tukhvatulin; Hayk Davtyan; Dmitry Shcheblyakov; Denis Logunov; Marina Chulkina; Anastasia Savilova; Dmitry Trofimov; Edward L Nelson; Michael G Agadjanyan; Ravshan I Ataullakhanov. 2014. "Targeting TLR-4 with a novel pharmaceutical grade plant derived agonist, Immunomax®, as a therapeutic strategy for metastatic breast cancer." Journal of Translational Medicine 12, no. 1: 322.
Toll-like receptors are the essential components of innate immunity. It is shown that TLRs play an essential role in the immune resistance of an organism to bacterial and viral infections. The binding of TLR to its own ligands results in the activation of several adapter molecules and kinases, inducing the activation of the main pro-inflammatory transcriptional factors, which in turn induce the activation of the main pro-inflammatory transcriptional factors. This activation results in the development of both the innate immune response triggered by the enhanced expression of a number of pro-inflammatory cytokines and antimicrobial peptides and that of the adaptive immune response, via the activation of dendritic cells and enhancement of antigen presentation, etc. The ability of TLR agonists to bolster the immune reaction makes them promising for use in the therapy of infectious diseases and in the chemotherapy of malignant neoformations. However, different TLR ligands may have either antitumor activity (lipopolysaccharide, imiquimod, CpG) or, conversely, could beef up the resistance of tumor cells to apoptosis, stimulating their proliferation under certain conditions (lipopolysaccharide, lipopeptide). It has been shown that the TLR2-dependent signalling pathway in the myelomonocytic mouse leukaemia cell line WEHI-3B leads to the constitutive activation of the transcriptional factor NF-kB, suppression of apoptosis in tumor cells, and progression of myelomonocytic mouse leukaemiain vivo, upon the addition of TLR2 agonist (synthetic lipopeptide Pam2CSK4) or following the infection of tumor cells withMycoplasma arginini.
D.V. Shcheblyakov; D.Y. Logunov; I.V. Rakovskaya; M.M. Shmarov; B.S. Naroditsky; A.L. Ginzburg. Triggering of Toll-like Receptor-2 in Mouse Myelomonocytic Leukaemia Cells WEHI-3B Leads to the Suppression of Apoptosis and Promotes Tumor Progression in Vivo. Acta Naturae 2011, 3, 83 -93.
AMA StyleD.V. Shcheblyakov, D.Y. Logunov, I.V. Rakovskaya, M.M. Shmarov, B.S. Naroditsky, A.L. Ginzburg. Triggering of Toll-like Receptor-2 in Mouse Myelomonocytic Leukaemia Cells WEHI-3B Leads to the Suppression of Apoptosis and Promotes Tumor Progression in Vivo. Acta Naturae. 2011; 3 (4):83-93.
Chicago/Turabian StyleD.V. Shcheblyakov; D.Y. Logunov; I.V. Rakovskaya; M.M. Shmarov; B.S. Naroditsky; A.L. Ginzburg. 2011. "Triggering of Toll-like Receptor-2 in Mouse Myelomonocytic Leukaemia Cells WEHI-3B Leads to the Suppression of Apoptosis and Promotes Tumor Progression in Vivo." Acta Naturae 3, no. 4: 83-93.