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Article ; Online: Allo-priming as a universal anti-viral vaccine: protecting elderly from current COVID-19 and any future unknown viral outbreak.

Har-Noy, Michael / Or, Reuven

Journal of translational medicine

2020 Volume 18, Issue 1, Page(s) 196

Abstract: Background: We present the rationale for a novel allo-priming approach to serve the elderly as a universal anti-virus vaccine, as well serving to remodel the aging immune system in order to reverse immunosenescence and inflammaging. This approach has ... ...

Abstract	Background: We present the rationale for a novel allo-priming approach to serve the elderly as a universal anti-virus vaccine, as well serving to remodel the aging immune system in order to reverse immunosenescence and inflammaging. This approach has the potential to protect the most vulnerable from disease and provide society an incalculable economic benefit. Allo-priming healthy elderly adults is proposed to provide universal protection from progression of any type of viral infection, including protection against progression of the current outbreak of COVID-19 infection, and any future variants of the causative SARS-CoV-2 virus or the next 'Disease X'. Allo-priming is an alternative approach for the COVID-19 pandemic that provides a back-up in case vaccination strategies to elicit neutralizing antibody protection fails or fails to protect the vulnerable elderly population. The allo-priming is performed using activated, intentionally mismatched, ex vivo differentiated and expanded living Th1-like cells (AlloStim Conclusion: Allo-priming has potential to provide universal protection from viral disease and is a strategy to reverse immunosenescence and counter-regulate chronic inflammation (inflammaging). Allo-priming can be used as an adjuvant for anti-viral vaccines and as a counter-measure for unknown biological threats and bio-economic terrorism.
MeSH term(s)	Adult ; Aged ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Antigen Presentation ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/immunology ; Coronavirus Infections/prevention & control ; Humans ; Immunologic Memory ; Pandemics/prevention & control ; Pneumonia, Viral/immunology ; Pneumonia, Viral/prevention & control ; SARS-CoV-2 ; Th1 Cells/immunology ; Viral Vaccines/immunology
Chemical Substances	Antibodies, Neutralizing ; Antibodies, Viral ; Viral Vaccines
Keywords	covid19
Language	English
Publishing date	2020-05-12
Publishing country	England
Document type	Journal Article
ISSN	1479-5876
ISSN (online)	1479-5876
DOI	10.1186/s12967-020-02363-3
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Allo-priming as a universal anti-viral vaccine

Michael Har-Noy / Reuven Or

Journal of Translational Medicine, Vol 18, Iss 1, Pp 1-

protecting elderly from current COVID-19 and any future unknown viral outbreak

2020 Volume 11

Abstract: Abstract Background We present the rationale for a novel allo-priming approach to serve the elderly as a universal anti-virus vaccine, as well serving to remodel the aging immune system in order to reverse immunosenescence and inflammaging. This approach ...

Abstract	Abstract Background We present the rationale for a novel allo-priming approach to serve the elderly as a universal anti-virus vaccine, as well serving to remodel the aging immune system in order to reverse immunosenescence and inflammaging. This approach has the potential to protect the most vulnerable from disease and provide society an incalculable economic benefit. Allo-priming healthy elderly adults is proposed to provide universal protection from progression of any type of viral infection, including protection against progression of the current outbreak of COVID-19 infection, and any future variants of the causative SARS-CoV-2 virus or the next ‘Disease X’. Allo-priming is an alternative approach for the COVID-19 pandemic that provides a back-up in case vaccination strategies to elicit neutralizing antibody protection fails or fails to protect the vulnerable elderly population. The allo-priming is performed using activated, intentionally mismatched, ex vivo differentiated and expanded living Th1-like cells (AlloStim®) derived from healthy donors currently in clinical use as an experimental cancer vaccine. Multiple intradermal injections of AlloStim® creates a dominate titer of allo-specific Th1/CTL memory cells in circulation, replacing the dominance of exhausted memory cells of the aged immune system. Upon viral encounter, by-stander activation of the allo-specific memory cells causes an immediate release of IFN-ϒ, leading to development of an “anti-viral state”, by-stander activation of innate cellular effector cells and activation of cross-reactive allo-specific CTL. In this manner, the non-specific activation of allo-specific Th1/CTL initiates a cascade of spatial and temporal immune events which act to limit the early viral titer. The release of endogenous heat shock proteins (HSP) and DAMP from lysed viral-infected cells, in the context of IFN-ϒ, creates of conditions for in situ vaccination leading to viral-specific Th1/CTL immunity. These viral-specific Th1/CTL provide sterilizing immunity and ...
Keywords	COVID-19 ; Immunosenescence ; Inflammaging ; Cell therapy ; Immunotherapy ; Vaccine ; Medicine ; R ; covid19
Subject code	570
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Allo-priming as a universal anti-viral vaccine

Har-Noy, Michael / Or, Reuven

Journal of Translational Medicine

protecting elderly from current COVID-19 and any future unknown viral outbreak

2020 Volume 18, Issue 1

Keywords	General Biochemistry, Genetics and Molecular Biology ; General Medicine ; covid19
Language	English
Publisher	Springer Science and Business Media LLC
Publishing country	us
Document type	Article ; Online
ISSN	1479-5876
DOI	10.1186/s12967-020-02363-3
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Allo-priming as a universal anti-viral vaccine: protecting elderly from current COVID-19 and any future unknown viral outbreak

Har-Noy, Michael / Or, Reuven

J Transl Med

Abstract: BACKGROUND: We present the rationale for a novel allo-priming approach to serve the elderly as a universal anti-virus vaccine, as well serving to remodel the aging immune system in order to reverse immunosenescence and inflammaging. This approach has the ...

Abstract	BACKGROUND: We present the rationale for a novel allo-priming approach to serve the elderly as a universal anti-virus vaccine, as well serving to remodel the aging immune system in order to reverse immunosenescence and inflammaging. This approach has the potential to protect the most vulnerable from disease and provide society an incalculable economic benefit. Allo-priming healthy elderly adults is proposed to provide universal protection from progression of any type of viral infection, including protection against progression of the current outbreak of COVID-19 infection, and any future variants of the causative SARS-CoV-2 virus or the next 'Disease X'. Allo-priming is an alternative approach for the COVID-19 pandemic that provides a back-up in case vaccination strategies to elicit neutralizing antibody protection fails or fails to protect the vulnerable elderly population. The allo-priming is performed using activated, intentionally mismatched, ex vivo differentiated and expanded living Th1-like cells (AlloStim®) derived from healthy donors currently in clinical use as an experimental cancer vaccine. Multiple intradermal injections of AlloStim® creates a dominate titer of allo-specific Th1/CTL memory cells in circulation, replacing the dominance of exhausted memory cells of the aged immune system. Upon viral encounter, by-stander activation of the allo-specific memory cells causes an immediate release of IFN-Ï, leading to development of an "anti-viral state", by-stander activation of innate cellular effector cells and activation of cross-reactive allo-specific CTL. In this manner, the non-specific activation of allo-specific Th1/CTL initiates a cascade of spatial and temporal immune events which act to limit the early viral titer. The release of endogenous heat shock proteins (HSP) and DAMP from lysed viral-infected cells, in the context of IFN-Ï, creates of conditions for in situ vaccination leading to viral-specific Th1/CTL immunity. These viral-specific Th1/CTL provide sterilizing immunity and memory for protection from disease recurrence, while increasing the pool of Th1/CTL in circulation capable of responding to the next viral encounter. CONCLUSION: Allo-priming has potential to provide universal protection from viral disease and is a strategy to reverse immunosenescence and counter-regulate chronic inflammation (inflammaging). Allo-priming can be used as an adjuvant for anti-viral vaccines and as a counter-measure for unknown biological threats and bio-economic terrorism.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #245284
Database	COVID19

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Article ; Online: Allo-priming as a universal anti-viral vaccine

Har-Noy, Michael / Or, Reuven

Journal of translational medicine, 18(1):196

protecting elderly from current COVID-19 and any future unknown viral outbreak

2020

Abstract: We present the rationale for a novel allo-priming approach to serve the elderly as a universal anti-virus vaccine, as well serving to remodel the aging immune system in order to reverse immunosenescence and inflammaging. This approach has the potential ... ...

Abstract	We present the rationale for a novel allo-priming approach to serve the elderly as a universal anti-virus vaccine, as well serving to remodel the aging immune system in order to reverse immunosenescence and inflammaging. This approach has the potential to protect the most vulnerable from disease and provide society an incalculable economic benefit. Allo-priming healthy elderly adults is proposed to provide universal protection from progression of any type of viral infection, including protection against progression of the current outbreak of COVID-19 infection, and any future variants of the causative SARS-CoV-2 virus or the next ‘Disease X’. Allo-priming is an alternative approach for the COVID-19 pandemic that provides a back-up in case vaccination strategies to elicit neutralizing antibody protection fails or fails to protect the vulnerable elderly population. The allo-priming is performed using activated, intentionally mismatched, ex vivo differentiated and expanded living Th1-like cells (AlloStim®) derived from healthy donors currently in clinical use as an experimental cancer vaccine. Multiple intradermal injections of AlloStim® creates a dominate titer of allo-specific Th1/CTL memory cells in circulation, replacing the dominance of exhausted memory cells of the aged immune system. Upon viral encounter, by-stander activation of the allo-specific memory cells causes an immediate release of IFN-ϒ, leading to development of an “anti-viral state”, by-stander activation of innate cellular effector cells and activation of cross-reactive allo-specific CTL. In this manner, the non-specific activation of allo-specific Th1/CTL initiates a cascade of spatial and temporal immune events which act to limit the early viral titer. The release of endogenous heat shock proteins (HSP) and DAMP from lysed viral-infected cells, in the context of IFN-ϒ, creates of conditions for in situ vaccination leading to viral-specific Th1/CTL immunity. These viral-specific Th1/CTL provide sterilizing immunity and memory for protection from disease recurrence, while increasing the pool of Th1/CTL in circulation capable of responding to the next viral encounter.
Keywords	COVID-19 ; Cell therapy ; Immunotherapy ; Immunosenescence ; Vaccine ; Inflammaging ; covid19
Language	English
Publishing country	de
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Proteomic analyses of different human tumour-derived chaperone-rich cell lysate (CRCL) anti-cancer vaccines reveal antigen content and strong similarities amongst the vaccines along with a basis for CRCL's unique structure: CRCL vaccine proteome leads to unique structure.

Mayer-Sonnenfeld, Tehila / Har-Noy, Michael / Lillehei, Kevin O / Graner, Michael W

International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group

2013 Volume 29, Issue 6, Page(s) 520–527

Abstract: Purpose: The aim of this paper was to compare protein content of chaperone-rich cell lysate (CRCL) anti-cancer vaccines prepared from human tumours of different histological origins to evaluate the uniformity of their protein content.: Materials and ... ...

Abstract	Purpose: The aim of this paper was to compare protein content of chaperone-rich cell lysate (CRCL) anti-cancer vaccines prepared from human tumours of different histological origins to evaluate the uniformity of their protein content. Materials and methods: Clinical grade CRCL was prepared under Good Manufacturing Practice (GMP) conditions from surgically resected human tumours (colorectal cancer, glioblastoma, non-small cell lung cancer, ovarian cancer). Protein samples were separated by SDS-PAGE and slices cut from gels for protease digestion followed by mass spectrometry analysis. Proteins were identified, and the content assessed by gene ontogeny/networking programmatic computation. CRCL preparations were also analysed by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Results: We identified between 200 and 550 proteins in the various CRCL preparations. Gene ontogeny analysis indicated that the vaccines showed clear relationships, despite different tumour origins. A total of 95 proteins were common to all the CRCLs. Networking analyses implicated heat shock proteins in antigen processing pathways, and showed connections to the cytoskeletal network. We found that CRCL vaccines showed a particulate structure by NTA, and TEM revealed an extended fence-like structural network in CRCL, with regions that were microns in size. Conclusions: We conclude that it is feasible to prepare and characterise CRCL from a variety of different tissue sources; a substantial portion of the protein content is identical among the different CRCLs, while the overall compositions also suggest high overlaps in functional categories. The protein content indicates the presence of antigens and implies a potential structure, which we believe may play a role in CRCL's ability to stimulate innate antigen presenting cell activation.
MeSH term(s)	Aged ; Antigens, Neoplasm/metabolism ; Cancer Vaccines ; Female ; Humans ; Male ; Middle Aged ; Molecular Chaperones/metabolism ; Neoplasms/immunology ; Neoplasms/metabolism ; Proteome ; Proteomics
Chemical Substances	Antigens, Neoplasm ; Cancer Vaccines ; Molecular Chaperones ; Proteome
Language	English
Publishing date	2013-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632526-9
ISSN	1464-5157 ; 0265-6736
ISSN (online)	1464-5157
ISSN	0265-6736
DOI	10.3109/02656736.2013.796529
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Article ; Online: Prolonged remission of advanced bronchoalveolar adenocarcinoma in a dog treated with autologous, tumour-derived chaperone-rich cell lysate (CRCL) vaccine.

Epple, Laura M / Bemis, Lynne T / Cavanaugh, Ryan P / Skope, Anne / Mayer-Sonnenfeld, Tehila / Frank, Chad / Olver, Christine S / Lencioni, Alex M / Dusto, Nathaniel L / Tal, Alona / Har-Noy, Michael / Lillehei, Kevin O / Katsanis, Emmanuel / Graner, Michael W

International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group

2013 Volume 29, Issue 5, Page(s) 390–398

Abstract: Purpose: This paper presents the treatment of a 12-year-old female spayed Great Dane who presented with vestibular signs (ataxia, nystagmus, hind end collapse). Thoracic radiographs revealed a discrete pulmonary nodule in the right cranial lung lobe. ... ...

Abstract	Purpose: This paper presents the treatment of a 12-year-old female spayed Great Dane who presented with vestibular signs (ataxia, nystagmus, hind end collapse). Thoracic radiographs revealed a discrete pulmonary nodule in the right cranial lung lobe. Ultrasound-guided fine needle aspirate detected primary bronchoalveolar adenocarcinoma, verified via computed tomography, with a second smaller nodule discovered in the right cranial lung lobe. Materials and methods: A lateral thoracotomy with right cranial lung lobectomy was performed. Histopathological analysis of the nodules and an excised lymph node identified grade III bronchoalveolar adenocarcinoma with vascular infiltration and lymph node metastasis - a grim diagnosis with a reported median survival time of 6-27 days. A 10-g sample of the tumour was processed into a chaperone-rich cell lysate (CRCL) vaccine, which was administered weekly to the patient. Imiquimod - a Toll-like receptor 7 (TLR7) agonist - was applied topically for the first 12 treatments to stimulate local Langerhans cells. A single injection of bacillus Calmette-Guerin (BCG) was administered for additional immune stimulation at week 30 of treatment. Results: The dog remained stable and in otherwise good health until diffuse relapse occurred 44 weeks after the initial treatment; following gastrointestinal bleeding, the dog was euthanised 50+ weeks post diagnosis. Conclusion: To the authors' knowledge, this is the first report of significantly prolonged survival following a diagnosis of grade III/stage III bronchoalveolar adenocarcinoma in a canine patient. This case report suggests that CRCL vaccine combined with topical imiquimod is a safe, effective treatment for canine tumours.
MeSH term(s)	Adenocarcinoma, Bronchiolo-Alveolar/diagnostic imaging ; Adenocarcinoma, Bronchiolo-Alveolar/pathology ; Adenocarcinoma, Bronchiolo-Alveolar/therapy ; Adenocarcinoma, Bronchiolo-Alveolar/veterinary ; Animals ; Cancer Vaccines/therapeutic use ; Dog Diseases/diagnostic imaging ; Dog Diseases/pathology ; Dog Diseases/therapy ; Dogs ; Female ; Lung/diagnostic imaging ; Lung/pathology ; Lung Neoplasms/diagnostic imaging ; Lung Neoplasms/pathology ; Lung Neoplasms/therapy ; Lung Neoplasms/veterinary ; Molecular Chaperones/immunology ; Radiography
Chemical Substances	Cancer Vaccines ; Molecular Chaperones
Language	English
Publishing date	2013-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632526-9
ISSN	1464-5157 ; 0265-6736
ISSN (online)	1464-5157
ISSN	0265-6736
DOI	10.3109/02656736.2013.800997
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Article ; Online: Th-1 lymphocytes induce dendritic cell tumor killing activity by an IFN-γ-dependent mechanism.

LaCasse, Collin J / Janikashvili, Nona / Larmonier, Claire B / Alizadeh, Darya / Hanke, Neale / Kartchner, Jessica / Situ, Elaine / Centuori, Sara / Har-Noy, Michael / Bonnotte, Bernard / Katsanis, Emmanuel / Larmonier, Nicolas

Journal of immunology (Baltimore, Md. : 1950)

2011 Volume 187, Issue 12, Page(s) 6310–6317

Abstract: Dendritic cells (DCs) encompass a heterogeneous population of cells capable of orchestrating innate and adaptive immune responses. The ability of DCs to act as professional APCs has been the foundation for the development and use of these cells as ... ...

Abstract	Dendritic cells (DCs) encompass a heterogeneous population of cells capable of orchestrating innate and adaptive immune responses. The ability of DCs to act as professional APCs has been the foundation for the development and use of these cells as vaccines in cancer immunotherapy. DCs are also endowed with the nonconventional property of directly killing tumor cells. The current study investigates the regulation of murine DC cytotoxic function by T lymphocytes. We provide evidence that CD4(+) Th-1, but not Th-2, Th-17 cells, or regulatory T cells, are capable of inducing DC cytotoxic function. IFN-γ was identified as the major factor responsible for Th-1-induced DC tumoricidal activity. Tumor cell killing mediated by Th-1-activated killer DCs was dependent on inducible NO synthase expression and NO production. Importantly, Th-1-activated killer DCs were capable of presenting the acquired Ags from the killed tumor cells to T lymphocytes in vitro or in vivo. These observations offer new possibilities for the application of killer DCs in cancer immunotherapy.
MeSH term(s)	Animals ; Antigen Presentation/genetics ; Antigen Presentation/immunology ; Bone Marrow Cells/cytology ; Bone Marrow Cells/immunology ; Bone Marrow Cells/metabolism ; Cell Line, Tumor ; Coculture Techniques ; Cytotoxicity, Immunologic/genetics ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Female ; Interferon-gamma/metabolism ; Interferon-gamma/physiology ; Mammary Neoplasms, Experimental/immunology ; Mammary Neoplasms, Experimental/pathology ; Mammary Neoplasms, Experimental/therapy ; Melanoma, Experimental/immunology ; Melanoma, Experimental/pathology ; Melanoma, Experimental/therapy ; Mice ; Mice, 129 Strain ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Receptors, Interferon/deficiency ; Receptors, Interferon/genetics ; Receptors, Interferon/physiology ; Th1 Cells/immunology ; Th1 Cells/metabolism ; Interferon gamma Receptor
Chemical Substances	Receptors, Interferon ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2011-11-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1101812
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Article ; Online: Allogeneic effector/memory Th-1 cells impair FoxP3+ regulatory T lymphocytes and synergize with chaperone-rich cell lysate vaccine to treat leukemia.

Janikashvili, Nona / LaCasse, Collin J / Larmonier, Claire / Trad, Malika / Herrell, Amanda / Bustamante, Sara / Bonnotte, Bernard / Har-Noy, Michael / Larmonier, Nicolas / Katsanis, Emmanuel

Blood

2010 Volume 117, Issue 5, Page(s) 1555–1564

Abstract: Therapeutic strategies combining the induction of effective antitumor immunity with the inhibition of the mechanisms of tumor-induced immunosuppression represent a key objective in cancer immunotherapy. Herein we demonstrate that effector/memory CD4(+) T ...

Abstract	Therapeutic strategies combining the induction of effective antitumor immunity with the inhibition of the mechanisms of tumor-induced immunosuppression represent a key objective in cancer immunotherapy. Herein we demonstrate that effector/memory CD4(+) T helper-1 (Th-1) lymphocytes, in addition to polarizing type-1 antitumor immune responses, impair tumor-induced CD4(+)CD25(+)FoxP3(+) regulatory T lymphocyte (Treg) immunosuppressive function in vitro and in vivo. Th-1 cells also inhibit the generation of FoxP3(+) Tregs from naive CD4(+)CD25(-)FoxP3(-) T cells by an interferon-γ-dependent mechanism. In addition, in an aggressive mouse leukemia model (12B1), Th-1 lymphocytes act synergistically with a chaperone-rich cell lysate (CRCL) vaccine, leading to improved survival and long-lasting protection against leukemia. The combination of CRCL as a source of tumor-specific antigens and Th-1 lymphocytes as an adjuvant has the potential to stimulate efficient specific antitumor immunity while restraining Treg-induced suppression.
MeSH term(s)	Animals ; Blotting, Western ; Cancer Vaccines/administration & dosage ; Cancer Vaccines/immunology ; Cell Extracts/administration & dosage ; Cell Extracts/immunology ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Forkhead Transcription Factors/metabolism ; Immunologic Memory/immunology ; Interferon-gamma/metabolism ; Leukemia, Experimental/immunology ; Leukemia, Experimental/therapy ; Lymphocytes, Tumor-Infiltrating/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Nude ; Mice, SCID ; Molecular Chaperones/immunology ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Helper-Inducer/immunology ; T-Lymphocytes, Helper-Inducer/metabolism ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/metabolism ; Tumor Cells, Cultured
Chemical Substances	Cancer Vaccines ; Cell Extracts ; Forkhead Transcription Factors ; Foxp3 protein, mouse ; Molecular Chaperones ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2010-12-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2010-06-288621
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Article: Allo-priming as a universal anti-viral vaccine: protecting elderly from current COVID-19 and any future unknown viral outbreak

Har-Noy, Michael

Journal of translational medicine, 18(1):196

2020

Abstract	We present the rationale for a novel allo-priming approach to serve the elderly as a universal anti-virus vaccine, as well serving to remodel the aging immune system in order to reverse immunosenescence and inflammaging. This approach has the potential to protect the most vulnerable from disease and provide society an incalculable economic benefit. Allo-priming healthy elderly adults is proposed to provide universal protection from progression of any type of viral infection, including protection against progression of the current outbreak of COVID-19 infection, and any future variants of the causative SARS-CoV-2 virus or the next ‘Disease X’. Allo-priming is an alternative approach for the COVID-19 pandemic that provides a back-up in case vaccination strategies to elicit neutralizing antibody protection fails or fails to protect the vulnerable elderly population. The allo-priming is performed using activated, intentionally mismatched, ex vivo differentiated and expanded living Th1-like cells (AlloStim®) derived from healthy donors currently in clinical use as an experimental cancer vaccine. Multiple intradermal injections of AlloStim® creates a dominate titer of allo-specific Th1/CTL memory cells in circulation, replacing the dominance of exhausted memory cells of the aged immune system. Upon viral encounter, by-stander activation of the allo-specific memory cells causes an immediate release of IFN-ϒ, leading to development of an “anti-viral state”, by-stander activation of innate cellular effector cells and activation of cross-reactive allo-specific CTL. In this manner, the non-specific activation of allo-specific Th1/CTL initiates a cascade of spatial and temporal immune events which act to limit the early viral titer. The release of endogenous heat shock proteins (HSP) and DAMP from lysed viral-infected cells, in the context of IFN-ϒ, creates of conditions for in situ vaccination leading to viral-specific Th1/CTL immunity. These viral-specific Th1/CTL provide sterilizing immunity and memory for protection from disease recurrence, while increasing the pool of Th1/CTL in circulation capable of responding to the next viral encounter.
Keywords	COVID-19 ; Cell therapy ; Immunosenescence ; Immunotherapy ; Inflammaging ; Vaccine
Language	English
Document type	Article
Database	Repository for Life Sciences

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