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Article ; Online: Early treatment with anti-α

Johnson, Samuel D / Knight, Lindsey A / Kumar, Narendra / Olwenyi, Omalla A / Thurman, Michellie / Mehra, Smriti / Mohan, Mahesh / Byrareddy, Siddappa N

Frontiers in immunology

2022 Volume 13, Page(s) 1001727

Abstract: Despite advances in combination antiretroviral therapy (cART), people living with HIV (PLWH) continue to experience gastrointestinal dysfunction. Infusions of anti- ... ...

Abstract	Despite advances in combination antiretroviral therapy (cART), people living with HIV (PLWH) continue to experience gastrointestinal dysfunction. Infusions of anti-α
MeSH term(s)	Animals ; Simian Immunodeficiency Virus ; Macaca mulatta ; Simian Acquired Immunodeficiency Syndrome ; Antibodies/therapeutic use ; Macrophages ; HIV Infections/drug therapy
Chemical Substances	Antibodies
Language	English
Publishing date	2022-11-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1001727
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Article: Peptide Nanoarray Scaffold Vaccine for SARS-COV-2 and Its Variants of Concerns.

Zagorski, Karen / Pandey, Kabita / Rajaiah, Rajesh / Olwenyi, Omalla / Bade, Aditya / Acharya, Arpan / Johnston, Morgan / Filliaux, Shaun / Lyubchenko, Yuri / Byrareddy, Siddappa

Research square

2022

Abstract: The current vaccine development strategies for the COVID-19 pandemic utilize whole inactive or attenuated viruses, virus-like particles, recombinant proteins, and antigen-coding DNA and mRNA with various delivery strategies. While highly effective, these ...

Abstract	The current vaccine development strategies for the COVID-19 pandemic utilize whole inactive or attenuated viruses, virus-like particles, recombinant proteins, and antigen-coding DNA and mRNA with various delivery strategies. While highly effective, these vaccine development strategies are time-consuming and often do not provide reliable protection for immunocompromised individuals, young children, and pregnant women. Here, we propose a novel modular vaccine platform to address these shortcomings using chemically synthesized peptides and identified based on the validated bioinformatic data about the target. The vaccine is based on the rational design of an immunogen containing two defined B-cell epitopes from the spike protein of SARS-Co-V2 and a universal T-helper epitope PADRE assembled on the DNA scaffold. The results demonstrate that this assembly is immunogenic and generates neutralizing antibodies against SARS-CoV-2 wild type and its variants of concerns (VOC). This newly designed peptide nanoarray scaffold vaccine is useful in controlling virus transmission in immunocompromised individuals, as well as individuals who are prone to vaccine-induced adverse reactions. Given that the immunogen is modular, epitopes or immunomodulatory ligands can be easily introduced in order to tailor the vaccine to the recipient. This also allows the already developed vaccine to be modified rapidly according to the identified mutations of the virus.
Language	English
Publishing date	2022-01-24
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-1206402/v1
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Article: miR-15a and miR-15b modulate natural killer and CD8

Pathania, Anup S / Prathipati, Philip / Olwenyi, Omalla A / Chava, Srinivas / Smith, Oghenetejiri V / Gupta, Subash C / Chaturvedi, Nagendra K / Byrareddy, Siddappa N / Coulter, Don W / Challagundla, Kishore B

Molecular therapy oncolytics

2022 Volume 25, Page(s) 308–329

Abstract: Neuroblastoma (NB) is an enigmatic and deadliest pediatric cancer to treat. The major obstacles to the effective immunotherapy treatments in NB are defective immune cells and the immune evasion tactics deployed by the tumor cells and the stromal ... ...

Abstract	Neuroblastoma (NB) is an enigmatic and deadliest pediatric cancer to treat. The major obstacles to the effective immunotherapy treatments in NB are defective immune cells and the immune evasion tactics deployed by the tumor cells and the stromal microenvironment. Nervous system development during embryonic and pediatric stages is critically mediated by non-coding RNAs such as micro RNAs (miR). Hence, we explored the role of miRs in
Language	English
Publishing date	2022-03-31
Publishing country	United States
Document type	Journal Article
ISSN	2372-7705
ISSN	2372-7705
DOI	10.1016/j.omto.2022.03.010
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Article ; Online: Mental Health Issues During and After COVID-19 Vaccine Era.

Pandey, Kabita / Thurman, Michellie / Johnson, Samuel D / Acharya, Arpan / Johnston, Morgan / Klug, Elizabeth A / Olwenyi, Omalla A / Rajaiah, Rajesh / Byrareddy, Siddappa N

Brain research bulletin

2021 Volume 176, Page(s) 161–173

Abstract: The COVID-19 pandemic has persisted for more than a year, and post-COVID-19 sequelae of neurological complications, including direct and indirect effects on the central nervous system (CNS), have been recognized. There is a plethora of evidence for ... ...

Abstract	The COVID-19 pandemic has persisted for more than a year, and post-COVID-19 sequelae of neurological complications, including direct and indirect effects on the central nervous system (CNS), have been recognized. There is a plethora of evidence for neurological, cognitive, and emotional deficits in COVID-19 patients. Acute neurological symptoms like neuroinflammation, cognitive impairment, loss of smell, and brain stroke are common direct effects among SARS-CoV-2 infected individuals. Work-associated stress, lockdowns, social distancing, and quarantine in response to contain SARS-CoV-2 have also affected the mental health of large populations, regardless of age. Public health emergencies have affected individuals and communities, resulting in emotional reactions and unhealthy behaviors. Although vaccines have been widely distributed and administered among large populations, vaccine hesitancy still exists and may be due to apprehension about vaccine efficacy, preliminary trials, and associated side effects. This review highlights the impact of COVID-19 on the CNS by outlining direct and indirect effects and factors contributing to the decline in people's mental health throughout the COVID-19 pandemic both during and after vaccine administration. Furthermore, we also discuss reasons for vaccine hesitancy and why some groups of people are deprived of vaccines. Finally, we touched upon the social determinants of mental health and their impact on disadvantaged populations during times of crisis which may help policymakers set up some action plans to mitigate the COVID-19 mental health turmoil during this ongoing pandemic.
MeSH term(s)	COVID-19/psychology ; COVID-19 Vaccines/administration & dosage ; Communicable Disease Control ; Humans ; Longitudinal Studies ; Mental Health/trends ; Pandemics/prevention & control ; Public Health ; SARS-CoV-2/pathogenicity ; Vaccination/psychology ; Vaccination/trends ; Vaccination Refusal/psychology ; Vaccination Refusal/trends ; Vaccines
Chemical Substances	COVID-19 Vaccines ; Vaccines
Language	English
Publishing date	2021-09-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	197620-5
ISSN	1873-2747 ; 0361-9230
ISSN (online)	1873-2747
ISSN	0361-9230
DOI	10.1016/j.brainresbull.2021.08.012
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Article ; Online: Modular nanoarray vaccine for SARS-CoV-2.

Zagorski, Karen / Pandey, Kabita / Rajaiah, Rajesh / Olwenyi, Omalla A / Bade, Aditya N / Acharya, Arpan / Johnston, Morgan / Filliaux, Shaun / Lyubchenko, Yuri L / Byrareddy, Siddappa N

Nanomedicine : nanotechnology, biology, and medicine

2022 Volume 46, Page(s) 102604

Abstract	The current vaccine development strategies for the COVID-19 pandemic utilize whole inactive or attenuated viruses, virus-like particles, recombinant proteins, and antigen-coding DNA and mRNA with various delivery strategies. While highly effective, these vaccine development strategies are time-consuming and often do not provide reliable protection for immunocompromised individuals, young children, and pregnant women. Here, we propose a novel modular vaccine platform to address these shortcomings using chemically synthesized peptides identified based on the validated bioinformatic data about the target. The vaccine is based on the rational design of an immunogen containing two defined B-cell epitopes from the spike glycoprotein of SARS-CoV-2 and the universal T-helper epitope PADRE. The epitopes were conjugated to short DNA probes and combined with a complementary scaffold strand, resulting in sequence-specific self-assembly. The immunogens were then formulated by conjugation to gold nanoparticles by three methods or by co-crystallization with epsilon inulin. BALB/C mice were immunized with each formulation, and the IgG immune responses and virus neutralizing titers were compared. The results demonstrate that this assembly is immunogenic and generates neutralizing antibodies against wildtype SARS-CoV-2 and the Delta variant.
MeSH term(s)	Pregnancy ; Mice ; Animals ; Female ; Humans ; SARS-CoV-2 ; COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus/chemistry ; Pandemics/prevention & control ; COVID-19/prevention & control ; Viral Vaccines ; Gold ; Mice, Inbred BALB C ; Metal Nanoparticles ; Antibodies, Neutralizing ; Epitopes, B-Lymphocyte/chemistry ; Antibodies, Viral ; Pregnancy Complications, Infectious
Chemical Substances	COVID-19 Vaccines ; Spike Glycoprotein, Coronavirus ; Viral Vaccines ; Gold (7440-57-5) ; Antibodies, Neutralizing ; Epitopes, B-Lymphocyte ; Antibodies, Viral ; spike protein, SARS-CoV-2
Language	English
Publishing date	2022-09-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, Non-U.S. Gov't
ZDB-ID	2183417-9
ISSN	1549-9642 ; 1549-9634
ISSN (online)	1549-9642
ISSN	1549-9634
DOI	10.1016/j.nano.2022.102604
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Article: Systems biology analyses reveal enhanced chronic morphine distortion of gut-brain interrelationships in simian human immunodeficiency virus infected rhesus macaques.

Olwenyi, Omalla A / Johnson, Samuel D / Bidokhti, Mehdi / Thakur, Vandana / Pandey, Kabita / Thurman, Michellie / Acharya, Arpan / Uppada, Srijayaprakash / Callen, Shannon / Giavedoni, Luis / Ranga, Udaykumar / Buch, Shilpa J / Byrareddy, Siddappa N

Frontiers in neuroscience

2022 Volume 16, Page(s) 1001544

Abstract: Background: Commonly used opioids, such as morphine have been implicated in augmented SIV/HIV persistence within the central nervous system (CNS). However, the extent of myeloid cell polarization and viral persistence in different brain regions remains ... ...

Abstract	Background: Commonly used opioids, such as morphine have been implicated in augmented SIV/HIV persistence within the central nervous system (CNS). However, the extent of myeloid cell polarization and viral persistence in different brain regions remains unclear. Additionally, the additive effects of morphine on SIV/HIV dysregulation of gut-brain crosstalk remain underexplored. Therefore, studies focused on understanding how drugs of abuse such as morphine affect immune dynamics, viral persistence and gut-brain interrelationships are warranted. Materials and methods: For a total of 9 weeks, rhesus macaques were ramped-up, and twice daily injections of either morphine ( Results: Flow Cytometry-based semi-supervised analysis revealed that morphine exposure led to exacerbated M1 (CD14/CD16)/M2 (CD163/CD206) polarization in activated microglia that spanned across diverse brain regions. This was accompanied by elevated SHIV DNA within the sites of neurogenesis-HIP and SVZ. HIP/SVZ CD16+ activated microglia positively correlated with SHIV DNA levels in the brain ( Conclusion: These findings are suggestive that morphine promotes CNS inflammation by altering receptor modulation, increasing myeloid brain activation, distorting gut-brain crosstalk, and causing selective enhancement of SHIV persistence in sites of neurogenesis.
Language	English
Publishing date	2022-10-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2022.1001544
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Article ; Online: Immuno-epidemiology and pathophysiology of coronavirus disease 2019 (COVID-19).

Olwenyi, Omalla A / Dyavar, Shetty Ravi / Acharya, Arpan / Podany, Anthony T / Fletcher, Courtney V / Ng, Caroline L / Reid, St Patrick / Byrareddy, Siddappa N

Journal of molecular medicine (Berlin, Germany)

2020 Volume 98, Issue 10, Page(s) 1369–1383

Abstract: Occasional zoonotic viral attacks on immunologically naive populations result in massive death tolls that are capable of threatening human survival. Currently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infectious agent that causes ...

Abstract	Occasional zoonotic viral attacks on immunologically naive populations result in massive death tolls that are capable of threatening human survival. Currently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infectious agent that causes coronavirus disease (COVID-19), has spread from its epicenter in Wuhan China to all parts of the globe. Real-time mapping of new infections across the globe has revealed that variable transmission patterns and pathogenicity are associated with differences in SARS-CoV-2 lineages, clades, and strains. Thus, we reviewed how changes in the SARS-CoV-2 genome and its structural architecture affect viral replication, immune evasion, and transmission within different human populations. We also looked at which immune dominant regions of SARS-CoV-2 and other coronaviruses are recognized by Major Histocompatibility Complex (MHC)/Human Leukocyte Antigens (HLA) genes and how this could impact on subsequent disease pathogenesis. Efforts were also placed on understanding immunological changes that occur when exposed individuals either remain asymptomatic or fail to control the virus and later develop systemic complications. Published autopsy studies that reveal alterations in the lung immune microenvironment, morphological, and pathological changes are also explored within the context of the review. Understanding the true correlates of protection and determining how constant virus evolution impacts on host-pathogen interactions could help identify which populations are at high risk and later inform future vaccine and therapeutic interventions.
MeSH term(s)	Betacoronavirus/immunology ; COVID-19 ; Coronavirus Infections/epidemiology ; Coronavirus Infections/immunology ; Coronavirus Infections/physiopathology ; Coronavirus Infections/virology ; Host-Pathogen Interactions/immunology ; Humans ; Immune Evasion/immunology ; Pandemics ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/immunology ; Pneumonia, Viral/physiopathology ; Pneumonia, Viral/virology ; SARS-CoV-2 ; Virus Replication/immunology
Keywords	covid19
Language	English
Publishing date	2020-08-18
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1223802-8
ISSN	1432-1440 ; 0946-2716
ISSN (online)	1432-1440
ISSN	0946-2716
DOI	10.1007/s00109-020-01961-4
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Article ; Online: Therapeutic implications of SARS-CoV-2 dysregulation of the gut-brain-lung axis.

Johnson, Samuel D / Olwenyi, Omalla A / Bhyravbhatla, Namita / Thurman, Michellie / Pandey, Kabita / Klug, Elizabeth A / Johnston, Morgan / Dyavar, Shetty Ravi / Acharya, Arpan / Podany, Anthony T / Fletcher, Courtney V / Mohan, Mahesh / Singh, Kamal / Byrareddy, Siddappa N

World journal of gastroenterology

2021 Volume 27, Issue 29, Page(s) 4763–4783

Abstract: The emergence and rapid spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 180 million confirmed cases resulting in over 4 million deaths worldwide with no clear end in sight for the coronavirus disease 19 (COVID- ...

Abstract	The emergence and rapid spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over 180 million confirmed cases resulting in over 4 million deaths worldwide with no clear end in sight for the coronavirus disease 19 (COVID-19) pandemic. Most SARS-CoV-2 exposed individuals experience mild to moderate symptoms, including fever, cough, fatigue, and loss of smell and taste. However, many individuals develop pneumonia, acute respiratory distress syndrome, septic shock, and multiorgan dysfunction. In addition to these primarily respiratory symptoms, SARS-CoV-2 can also infiltrate the central nervous system, which may damage the blood-brain barrier and the neuron's synapses. Resultant inflammation and neurodegeneration in the brain stem can further prevent efferent signaling to cranial nerves, leading to the loss of anti-inflammatory signaling and normal respiratory and gastrointestinal functions. Additionally, SARS-CoV-2 can infect enterocytes resulting in gut damage followed by microbial dysbiosis and translocation of bacteria and their byproducts across the damaged epithelial barrier. As a result, this exacerbates pro-inflammatory responses both locally and systemically, resulting in impaired clinical outcomes. Recent evidence has highlighted the complex interactions that mutually modulate respiratory, neurological, and gastrointestinal function. In this review, we discuss the ways SARS-CoV-2 potentially disrupts the gut-brain-lung axis. We further highlight targeting specific responses to SARS-CoV-2 for the development of novel, urgently needed therapeutic interventions. Finally, we propose a prospective related to the individuals from Low- and Middle-Income countries. Here, the underlying propensity for heightened gut damage/microbial translocation is likely to result in worse clinical outcomes during this COVID-19 pandemic.
MeSH term(s)	Brain ; COVID-19 ; Humans ; Lung ; Pandemics ; Prospective Studies ; SARS-CoV-2
Language	English
Publishing date	2021-08-18
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2185929-2
ISSN	2219-2840 ; 1007-9327
ISSN (online)	2219-2840
ISSN	1007-9327
DOI	10.3748/wjg.v27.i29.4763
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Article ; Online: Chronic morphine administration differentially modulates viral reservoirs in SIVmac251 infected rhesus macaque model.

Acharya, Arpan / Olwenyi, Omalla A / Thurman, Michellie / Pandey, Kabita / Morsey, Brenda M / Lamberty, Benjamin / Ferguson, Natasha / Callen, Shannon / Fang, Qiu / Buch, Shilpa J / Fox, Howard S / Byrareddy, Siddappa N

Journal of virology

2020 Volume 95, Issue 5

Abstract: HIV persists in cellular reservoirs despite effective combined antiretroviral therapy (cART) and there is viremia flare up upon therapy interruption. Opioids modulate the immune system and suppress antiviral gene responses, which significantly impact ... ...

Abstract	HIV persists in cellular reservoirs despite effective combined antiretroviral therapy (cART) and there is viremia flare up upon therapy interruption. Opioids modulate the immune system and suppress antiviral gene responses, which significantly impact people living with HIV (PLWH). However, the effect of opioids on viral reservoir dynamics remain elusive. Herein, we developed a morphine dependent SIVmac251 infected
Language	English
Publishing date	2020-12-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.01657-20
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Article ; Online: Immuno-epidemiology and pathophysiology of coronavirus disease 2019 (COVID-19)

Olwenyi, Omalla A. / Dyavar, Shetty Ravi / Acharya, Arpan / Podany, Anthony T. / Fletcher, Courtney V. / Ng, Caroline L. / Reid, St Patrick / Byrareddy, Siddappa N.

Journal of Molecular Medicine

2020 Volume 98, Issue 10, Page(s) 1369–1383

Keywords	Genetics(clinical) ; Molecular Medicine ; Drug Discovery ; covid19
Language	English
Publisher	Springer Science and Business Media LLC
Publishing country	us
Document type	Article ; Online
ZDB-ID	1223802-8
ISSN	1432-1440 ; 0946-2716
ISSN (online)	1432-1440
ISSN	0946-2716
DOI	10.1007/s00109-020-01961-4
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