Review
Medical Laboratory Technology
Sita Awasthi, Harvey M. Friedman
Summary: The rapid development of two nucleoside-modified mRNA vaccines has revolutionized the field of COVID-19 vaccines with their safety and high effectiveness. The mRNA technology offers advantages such as accelerated immunogen discovery, robust immune response induction, and rapid manufacturing scale-up. Developing a genital herpes vaccine has been a longstanding public health priority, and the advent of mRNA technology holds promise in changing the narrative. The development of nucleoside-modified mRNA-lipid nanoparticle vaccines for genital herpes shows great potential in inducing higher levels of neutralizing antibodies and more durable immune responses compared to protein-adjuvanted vaccines.
TRANSLATIONAL RESEARCH
(2022)
Article
Medicine, Research & Experimental
Sita Awasthi, James J. Knox, Angela Desmond, Mohamad-Gabriel Alameh, Brian T. Gaudette, John M. Lubinski, Alexis Naughton, Lauren M. Hook, Kevin P. Egan, Ying K. Tam, Norbert Pardi, David Allman, Eline T. Luning Prak, Michael P. Cancro, Drew Weissman, Gary H. Cohen, Harvey M. Friedman
Summary: Nucleoside-modified mRNA vaccines show more durable protection in animal models compared to protein vaccines, with higher neutralizing antibody titers and robust B cell immune memory. The correlation between high neutralizing titers and B cell immune memory likely explains the more lasting protection provided by the mRNA vaccine.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Immunology
Jingjing Zhang, Xingli Xu, Suqin Duan, Yang Gao, Danjing Ma, Rong Yue, Fengyuan Zeng, Xueqi Li, Ziyan Meng, Xinghang Li, Zhenye Niu, Guorun Jiang, Li Yu, Yun Liao, Dandan Li, Lichun Wang, Heng Zhao, Ying Zhang, Qihan Li
Summary: This study revealed the strategy of how HSV-1 infection of dendritic cells interferes with the immune system, by investigating the impact of virus infection on both innate and adaptive immunity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Cooper K. Hayes, Christopher K. Villota, Fiona B. McEnany, Stacey Ceron, Sita Awasthi, Moriah L. Szpara, Harvey M. Friedman, David A. Leib, Richard Longnecker, Matthew D. Weitzman, Lisa N. Akhtar
Summary: Clinical HSV-2 isolates collected from neonates with encephalitis are more neurovirulent in human neuronal cell culture and murine models as compared to isolates from neonates with skin-limited disease, suggesting that viral factors contribute to neurologic outcome following human neonatal infection.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Review
Immunology
Christine Johnston
Summary: This article discusses the management of genital herpes infection and provides recommendations based on a systematic literature review, serving as a basis for updating the treatment guidelines.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Virology
Lucas Khellaf, Fabrice Bouscarat, Sonia Burrel, Nadhira Fidouh, Lorry Hachon, Margot Bucau, Sylvie Lariven, David Boutolleau, Veronique Joly, Jade Ghosn, Diane Le Pluart, Michael Thy
Summary: This study described two novel potential HSV-2 resistance mutations in an obese patient with a pseudotumoral genital HSV-related lesion, outlining consecutive antiviral treatments and the emergence of resistance. The research highlights the need for further data on antiviral dosage adaptation based on patient profiles.
JOURNAL OF MEDICAL VIROLOGY
(2022)
Review
Virology
Hemant Borase, Deepak Shukla
Summary: This review summarizes the pathogenesis of HSV-2 and its cellular interactions, explores new strategies and challenges in regulating HSV-2 replication and influencing the cell cycle through host cellular components, and presents a fresh perspective on the treatment of HSV-2 by targeting cellular proteins and pathways.
Article
Public, Environmental & Occupational Health
Noor Motea Abdo, Irfan Aslam, Shazia Irfan, Junu A. A. George, Ahmed R. R. Alsuwaidi, Luai A. A. Ahmed, Rami H. H. Al-Rifai
Summary: This study investigated the prevalence of HSV-2 infection among patients seeking fertility treatment in the UAE and found that approximately 10% of patients were exposed to HSV-2. HSV-2 infection was more common in males, patients with secondary infertility, and those with abnormal semen analysis.
FRONTIERS IN PUBLIC HEALTH
(2022)
Article
Virology
Tajanna Stinn, Steve Kuntz, Dana Varon, Meei-Li Huang, Stacy Selke, Samuel Njikan, Emily S. Ford, Joan Dragavon, Robert W. Coombs, Christine Johnston, Marta E. Bull
Summary: This study suggests that subclinical HSV shedding in HIV/HSV-coinfected women during ART may sustain HIV tissue reservoirs through antigen exposure or HIV replication. Frequent subclinical HSV DNA shedding was associated with increased HIV DNA tissue concentrations and increased divergence from ancestral sequences, indicating a potential role of immune responses to common coinfections in sustaining HIV tissue reservoirs during suppressive ART.
JOURNAL OF VIROLOGY
(2021)
Article
Ophthalmology
Sanya Yadav, Patrick Commiskey, Regis P. Kowalski, Vishal Jhanji
Summary: This study retrospectively reviewed cases of HSV-2 blepharokeratoconjunctivitis between 1995 and 2021, finding that while HSV-2 is an uncommon cause of keratitis, recurrence can still occur despite antiviral prophylaxis.
CURRENT EYE RESEARCH
(2022)
Review
Microbiology
Hongyan Guo, Heather S. Koehler, Richard D. Dix, Edward S. Mocarski
Summary: HSV1 is a common human pathogen that can cause oral and ocular diseases. Host immune mechanisms and cell death pathways play important roles in controlling HSV1 infection, while the virus has evolved strategies to evade host cell death.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Bishajit Sarkar, Md. Asad Ullah, Yusha Araf, Sowmen Das, Md. Hasanur Rahman, Abu Tayab Moin
Summary: HSV is a highly infectious virus with two types, HSV-1 and HSV-2, infecting millions worldwide. This study designed three polyvalent subunit vaccines targeting multiple strains of HSV, which showed stability and potential effectiveness through molecular docking and simulation studies. Validation of these vaccines in wet lab-based studies is still needed.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Virology
Abigail L. Whitford, Corinne A. Clinton, E. B. Lane Kennedy, Sara A. Dochnal, Jon B. Suzich, Anna R. Cliffe
Summary: The cellular protein DLK plays an essential role in the reactivation of herpes simplex virus, and the mechanisms of gene expression during reactivation are distinct from replication.
JOURNAL OF VIROLOGY
(2022)
Review
Immunology
Iara M. M. Backes, David A. A. Leib, Margaret E. E. Ackerman
Summary: The fetal/neonatal period is a critical stage for interventions and also a vulnerable period for viral infections. Maternal transfer of antibodies can reduce the risk of neonatal herpes simplex virus (nHSV) infections. Exploring the combination of antibody-based interventions and antiviral therapy is important for reducing infant mortality and long-term morbidity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Dor Rafael, Enosh Tomer, Oren Kobiler
Summary: Latent infection is a characteristic feature of herpesviruses, where the number of latent viral genomes reactivating per cell is limited and typically only one genome reactivates in each cell.
MICROBIOLOGY SPECTRUM
(2022)
Article
Multidisciplinary Sciences
Charlotte A. James, Yuexin Xu, Melissa S. Aguilar, Lichen Jing, Erik D. Layton, Martine Gilleron, Adriaan J. Minnaard, Thomas J. Scriba, Cheryl L. Day, Edus H. Warren, David M. Koelle, Chetan Seshadri
Summary: This study reveals the importance of CD4 and CD8 co-receptors in recognizing mycobacterial glycolipid antigens. The expression of either CD4 or CD8 increases the avidity of T cell receptors for mycolipids, leading to a higher intensity of fluorescence and decreased secretion threshold for interferon-gamma. Furthermore, CD8+ T cells show greater cytotoxicity compared to CD4+ T cells in individuals with active tuberculosis.
NATURE COMMUNICATIONS
(2022)
Article
Virology
Kerry J. Laing, Victoria L. Campbell, Lichun Dong, David M. Koelle
Summary: HLA-B*57:01 is associated with positive outcomes during viral infections through interactions with T cells and NK cells, but can lead to severe disease when treated with the anti-HIV-1 drug abacavir. In this study, a CD8 T-cell epitope in the ICP22 (US1) protein of HSV-2 that is restricted by HLA-B*57:01 was identified. The tetramer of this epitope was found to bind both CD8 T cells and NK cells, suggesting a mechanism for the recognition of HSV infection by NK cells or KIR-expressing T cells via KIR3DL1.
Article
Medicine, Research & Experimental
Oriol Mitja, Gilmar Reis, David R. Boulware, Adam M. Spivak, Ammar Sarwar, Christine Johnston, Brandon Webb, Michael D. Hill, Davey Smith, Peter Kremsner, Marla Curran, David Carter, Jim Alexander, Marc Corbacho, Todd C. Lee, Katherine Huppler Hullsiek, Emily G. McDonald, Rachel Hess, Michael Hughes, Jared M. Baeten, Ilan Schwartz, Luanne Metz, Lawrence Richer, Kara W. Chew, Eric Daar, David Wohl, Michael Dunne
Summary: This study conducted a pooled analysis of individual participant data from 11 randomized controlled trials to evaluate the efficacy of hydroxychloroquine (HCQ) in outpatients with mild COVID-19. The results suggest that HCQ does not show significant effects on viral clearance and hospitalization rate, and therefore, the use of HCQ in mild COVID-19 outpatients should be discontinued to reduce the risk of disease progression.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Article
Medicine, General & Internal
Sachin Silva, Houssein H. Ayoub, Christine Johnston, Rifat Atun, Laith J. Abu-Raddad
Summary: This study estimated the economic and quality-of-life losses due to genital herpes in low- and middle-income countries (LMICs) and the potential contribution of herpes simplex virus type 2 (HSV-2) infections to HIV transmission. The findings showed that the economic losses caused by genital herpes can be substantial, and the quality-of-life losses outweigh the spending on treatment and productivity reduction. If HSV-2 has indeed contributed to the spread of HIV, then a significant proportion of the costs associated with HIV treatment and wage losses can be attributed to HSV-2. Therefore, developing a vaccine against HSV-2 should be a global priority.
Article
Hematology
Chaitra Ujjani, Ted A. Gooley, Stephen E. Spurgeon, Deborah M. Stephens, Catherine Lai, Catherine M. Broome, Susan O'Brien, Haiying Zhu, Kerry J. Laing, Allison M. Winter, Georgios Pongas, Alexander L. Greninger, David M. Koelle, Tanya Siddiqi, Matthew S. Davids, Kerry A. Rogers, Alexey V. Danilov, Amy Sperling, Brian Tu, Tyler Sorensen, Kelsey Launchbury, Carlissa J. Burrow, Genesis Quezada, Joshua A. Hill, Mazyar Shadman, Philip A. Thompson
Summary: This study aimed to analyze the immune responses of patients with chronic lymphocytic leukemia (CLL) to the COVID-19 vaccine, including T-cell responses, and the impact of CLL therapeutics. The study found that patients receiving B-cell-directed therapy were less likely to have immune conversion. Additionally, the immune response persisted at 6 months, and administration of booster vaccinations enhanced the immune response. However, caution should be exercised as newer variants emerge and escape vaccine-induced immunity.
Article
Biochemistry & Molecular Biology
Yashpal S. Chhonker, Nusrat Ahmed, Christine M. Johnston, Ruanne V. Barnabas, Daryl J. Murry
Summary: Vitamin D is crucial for bone development and maintenance, as well as other physiological functions. Lower levels of serum vitamin D have been associated with severity of infection in COVID-19 patients. We developed and validated a robust LC-MS/MS method for quantitation of vitamin D and its metabolites in human dried blood spot samples. This method provides sensitive and accurate measurement, and can be applied to investigate the role of these compounds in various physiological processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Michiel van Gent, Werner J. D. Ouwendijk, Victoria L. Campbell, Kerry J. Laing, Georges M. G. M. Verjans, David M. Koelle
Summary: This study suggests that VZV-specific CD8 T-cells play a limited role in maintaining latent infection of varicella-zoster virus in human trigeminal ganglia.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Virology
Linhui Hao, Tien-Ying Hsiang, Ronit R. Dalmat, Renee Ireton, Jennifer F. Morton, Caleb Stokes, Jason Netland, Malika Hale, Chris Thouvenel, Anna Wald, Nicholas M. Franko, Kristen Huden, Helen Y. Chu, Alex Sigal, Alex L. Greninger, Sasha Tilles, Lynn K. Barrett, Wesley C. Van Voorhis, Jennifer Munt, Trevor Scobey, Ralph S. Baric, David J. Rawlings, Marion Pepper, Paul K. Drain, Michael Gale
Summary: New variants of SARS-CoV-2 continue to emerge and evade immunity. Convalescence from the ancestral virus provides limited protection against variants. Vaccination enhances immunity against viral variants, but the protection is weaker against Omicron BA.1, and a three-dose vaccine regimen provides significantly better protection against it compared to a two-dose.
Article
Medicine, Research & Experimental
Daniel Corey, Francoise Haeseleer, Joe Hou, Lawrence Corey
Summary: Adoptive therapy using genetically engineered T cells shows promise in treating infectious diseases in immunocompromised individuals. In this study, chimeric engulfment receptor (CER) T cells designed to recognize phosphatidylserine (PS)-expressing cells successfully eliminated SIV-infected cells. The introduction of innate immune functions into T cells enhances the elimination of SIV-infected cells, and further in vivo studies are needed to evaluate their effectiveness.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Editorial Material
Ethics
Tara M. Babu, Anna Wald
AMERICAN JOURNAL OF BIOETHICS
(2023)
Editorial Material
Pharmacology & Pharmacy
Jia Zhu, Hasan E. Abaci
Summary: The timely intervention of preventative and therapeutic measures has mitigated the global outbreak of mpox in 2022. However, further investigation is needed due to the high transmissibility and unique pathological characteristics of mpox. This article discusses the potential of a human skin-on-a-chip model for evaluating mpox disease, aiming to achieve a comprehensive understanding of its physiology and improve therapeutic predictions.
TRENDS IN PHARMACOLOGICAL SCIENCES
(2023)
Article
Immunology
Deborah Donnell, Fei Gao, James P. Hughes, Brett Hanscom, Lawrence Corey, Myron S. Cohen, Srilatha Edupuganti, Nyaradzo Mgodi, Helen Rees, Jared M. Baeten, Glenda Gray, Linda-Gail Bekker, Mina Hosseinipour, Sinead Delany-Moretlwe
Summary: This study used counterfactual placebo comparisons using other data sources to evaluate the efficacy of antiretroviral agents for HIV pre-exposure prophylaxis. The findings showed that injectable cabotegravir (CAB-LA) and daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) can significantly reduce the risk of HIV infection compared to no intervention, and the efficacy of FTC/TDF against counterfactual placebo was consistent with previous placebo-controlled trials.
JOURNAL OF THE INTERNATIONAL AIDS SOCIETY
(2023)
Article
Immunology
Emily S. Ford, Koshlan Mayer-Blackwell, Lichen Jing, Kerry J. Laing, Anton M. Sholukh, Russell St. Germain, Emily L. Bossard, Hong Xie, Thomas H. Pulliam, Saumya Jani, Stacy Selke, Carlissa J. Burrow, Christopher L. McClurkan, Anna Wald, Alexander L. Greninger, Michael R. Holbrook, Brett Eaton, Elizabeth Eudy, Michael Murphy, Elena Postnikova, Harlan S. Robins, Rebecca Elyanow, Rachel M. Gittelman, Matyas Ecsedi, Elise Wilcox, Aude G. Chapuis, Andrew Fiore-Gartland, David M. Koelle
Summary: Hybrid immunity, resulting from a combination of vaccination and previous infection, offers greater protection against SARS-CoV-2 than either vaccination or prior infection alone. This study investigated the dynamics of spike-reactive T cells in individuals with hybrid immunity, following either SARS-CoV-2 infection or mRNA vaccination. The findings show that vaccination leads to expansions of memory T cell clones, while also generating diverse new T cell clones. The study provides insights into T cell responses to vaccines and emerging pathogens.
Article
Multidisciplinary Sciences
Sijie Sun, Lei Jin, Ying Zheng, Jia Zhu
Summary: A vascularized 3D "skin-on-chip" model has been developed to mimic human skin architecture and investigate Herpes simplex virus (HSV) infection, showing that perfusion with an antiviral drug can inhibit the infection.
NATURE COMMUNICATIONS
(2022)
Meeting Abstract
Medicine, General & Internal
S. Wanner, V. L. Campbell, S. Selke, D. M. Koelle
JOURNAL OF INVESTIGATIVE MEDICINE
(2022)