Article
Infectious Diseases
Jose Molto, Miriam Rosas-Umbert, Cristina Miranda, Christian Manzardo, Maria C. Puertas, Marta Ruiz-Riol, Miriam Lopez, Jose M. Miro, Javier Martinez-Picado, Bonaventura Clotet, Christian Brander, Beatriz Mothe, Marta Valle
Summary: The pharmacokinetics of romidepsin as an HIV latency reversing agent were best described by a three-compartment model with linear kinetics. Higher exposure to romidepsin was associated with increased expression of apoptosis markers in T cells and declines in CD4+ count. However, romidepsin exposure did not increase viral reactivation levels.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2021)
Article
Immunology
Jose A. Munoz-Moreno, Sara Carrillo-Molina, Ignacio Martinez-Zalacain, Cristina Miranda, Christian Manzardo, Pep Coll, Michael Meulbroek, Tomas Hanke, Maite Garolera, Josep M. Miro, Christian Brander, Bonaventura Clotet, Carles Soriano-Mas, Jose Molto, Beatriz Mothe
Summary: This study aimed to assess the impact of a kick&kill HIV cure strategy on the central nervous system (CNS) using a therapeutic vaccine and a latency-reversing agent. The results showed no detrimental effects on cognitive status, functional outcomes, or brain imaging parameters in early-treated HIV-infected individuals. The safety of CNS was also confirmed after the treatment.
Review
Virology
Katherine M. Bricker, Ann Chahroudi, Maud Mavigner
Summary: The "shock and kill" strategy for treating HIV-1 involves reactivating latent infected cells with LRAs, exposing them to immune system killing. Progress has been made in this area through the NHP model, which has both advantages and limitations for evaluating treatment efficacy.
Article
Chemistry, Organic
Mizushi Yanagihara, Kenichi Murai, Naoki Kishimoto, Towa Abe, Shogo Misumi, Mitsuhiro Arisawa
Summary: The total synthesis and biological evaluation of the marine sesterterpenoid ansellone A, along with its analogues, were successfully carried out. The key to the success of the synthetic route was the Prins cyclization reaction enabled by the strategic use of the TfO group to stabilize the acid-labile tertiary allylic alcohol. The structure-activity relationship study indicated that the alcohol analogue exhibited more potent activity than compound 1.
Article
Biotechnology & Applied Microbiology
Preethi B. Balakrishnan, Carissa S. Holmberg, Debbie K. Ledezma, Alberto Bosque, Rohan Fernandes
Summary: This study investigates the use of nanoparticles as carriers to deliver drugs for the reactivation of latent HIV infection. The results show that polymeric-coated nanoparticles are more effective than free polymers in activating latent HIV and enhancing immune activation.
Article
Medicine, Research & Experimental
Mohsen Sheykhhasan, Aidin Foroutan, Hamed Manoochehri, Saeideh Gholamzadeh Khoei, Naresh Poondla, Massoud Saidijam
Summary: HIV/AIDS remains a major global public health issue, with gene therapy showing promising results in combating HIV infection. Traditional treatment methods have limitations and side effects, making gene therapy an effective alternative.
Article
Medicine, Research & Experimental
Dennis C. Copertino, Carissa S. Holmberg, Jared Weiler, Adam R. Ward, J. Natalie Howard, Callie Levinger, Alina P. S. Pang, Michael J. Corley, Friederike Duendar, Paul Zumbo, Doron Betel, Rajesh T. Gandhi, Deborah K. McMahon, Ronald J. Bosch, Noemi Linden, Bernard J. Macatangay, Joshua C. Cyktor, Joseph J. Eron, John W. Mellors, Colin Kovacs, Erika Benko, Alberto Bosque, R. Brad Jones
Summary: IL-15 combined with HODHBt enhances HIV-specific cytotoxic T cell responses and reduces HIV latency.
Review
Biochemistry & Molecular Biology
Christopher Zaab-Yen Abana, Helena Lamptey, Evelyn Y. Bonney, George B. Kyei
Summary: Finding a cure for HIV is necessary to address the limitations of current therapy, including lack of complete cure, side effects, high costs, and drug resistance. Current approaches to HIV cure include boosting the host immune system, genetic methods, and clearing cells harboring latent HIV.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Immunology
Jose A. Moran, Shireen R. Turner, Matthew D. Marsden
Summary: This article discusses the biological sex differences in HIV infection and their importance in viral acquisition, pathogenesis, treatment, and cure efforts.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Anna Kula-Pacurar, Anthony Rodari, Gilles Darcis, Carine Van Lint
Summary: The shock-and-kill strategy relies on latency reversing agents (LRAs) to reactivate HIV-1 and induce immune responses or cytopathic effects for elimination of latent virus. LRAs, particularly immunomodulatory ones, show potential for controlling HIV transcription pathways, but the precise mechanisms are not fully understood, complicating efforts to develop more efficient and safer cure strategies. Deciphering these mechanisms is crucial in designing approaches to eliminate latent HIV infection.
SEMINARS IN IMMUNOLOGY
(2021)
Article
Chemistry, Medicinal
Dong Huang, Lian-Shuai Ding, Fang-Yu Yuan, Shu-Qi Wu, Han-Zhuang Weng, Xiao-Qing Tian, Gui-Hua Tang, Cheng-Qi Fan, Xiang Gao, Sheng Yin
Summary: Marine toxins (MTs) are complex natural products with unique toxicological and pharmacological activities. This study isolated okadaic acid (OA) and OA methyl ester from a microalgae strain and conducted structural modifications to develop more tolerable and potent latency reversing agents (LRAs). Compound 7 showed stronger activity and less cytotoxicity, and it was found that the carboxyl group in OA was essential for activity. Mechanistic study revealed that compound 7 promotes the dissociation of P-TEFb to reactivate latent HIV-1.
Article
Immunology
Bright Agbodzi, Francine Berlange Sado Yousseu, Fredy Brice Nemg Simo, Selassie Kumordjie, Clara Yeboah, Mba-Tihssommah Mosore, Ronald E. Bentil, Heather G. Coatsworth, Naiki Attram, Shirley Nimo-Paintsil, Anne T. Fox, Joseph H. K. Bonney, William Ampofo, Rhoel R. Dinglasan, Terrel Sanders, Michael R. Wiley, Maurice Demanou, Andrew G. Letizia
Summary: Dengue fever is a global public health threat, including in African countries. Cameroon has experienced sporadic cases of arboviral infections, including dengue fever. Genomic analyses were conducted to investigate the origin and phylogenetic profile of DENV-1 outbreak strains in Cameroon and predict the impact of emerging therapeutics on these strains.
EMERGING MICROBES & INFECTIONS
(2023)
Review
Immunology
Adam R. Ward, Talia M. Mota, R. Brad Jones
Summary: Combination antiretroviral therapy has proven successful for treating HIV, but a cure remains elusive due to mechanisms of HIV persistence. Different approaches aim for durable viral control or complete eradication, with overcoming barriers such as viral latency and immune resistance being key. Immune-mediated control in some PLWH offers hope for an immunological approach to cure, requiring safe, effective, and scalable strategies.
SEMINARS IN IMMUNOLOGY
(2021)
Review
Medicine, General & Internal
Lilly M. Wong, Guochun Jiang
Summary: HIV cure is hindered by the presence of quiescent yet replication competent HIV-1, but current research in NF-kappa B signaling pathways shows promise. Both canonical and noncanonical NF-kappa B signaling have been found to promote latency reversal and expression of HIV from reservoirs, offering new avenues for potential functional cure strategies.
Article
Infectious Diseases
Philippe Selhorst, Sebastian Lequime, Gytis Dudas, Sam Proesmans, Pascal Lutumba, Freddy Katshongo, Kadrie Ramadan, Isabel Micalessi, Steve Ahuka-Mundeke, Veerle Vanlerberghe, Marjan Van Esbroeck, Kevin K. Arien
Summary: The origin and spread of dengue virus (DENV) circulating in Africa were studied by sequencing serum samples from the Democratic Republic of Congo and febrile travelers returning from Africa. The results showed that DENV in Africa mainly originated from Asia through multiple introductions. Genomic surveillance of DENV in Africa can help with early outbreak response and limit virus spread and human disease burden.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Immunology
Erich S. Tusch, Lene Ryom, Olga Fursa, Lars Peters, Lars Ostergaard, Eric Florence, Simon Edwards, Christian Hoffmann, Helen Sambatakou, Peter Reiss, Eduardo Shahar, Dag Henrik Reikvam, Brigitte Schmied, Dzmitry Paduta, Alexei Yakovlev, Janos Szlavik, Jovan Ranin, Kai Zilmer, Vilma Uzdaviniene, Annegret Pelchen-Matthews, Amanda Mocroft, Joanne Reekie
Summary: This study aimed to investigate the incidence and risk factors of mortality among people with HIV due to suicide, substance use, and violence/accident. The results showed that a recent AIDS diagnosis and HIV infection acquired through injection drug use were associated with an increased risk of death due to substance use and violent/accidental deaths.
Article
Immunology
Maarten van Wijhe, Kamille Fogh, Steen Ethelberg, Kasper Karmark Iversen, Henrik Nielsen, Lars Ostergaard, Berit Andersen, Henning Bundgaard, Charlotte S. Jorgensen, Bibi F. Ss Scharff, Svend Ellermann-Eriksen, Isik S. Johansen, Anders Fomsgaard, Tyra Grove Krause, Lothar Wiese, Thea K. Fischer, Kare Molbak, Thomas Benfield, Fredrik Folke, Freddy Lippert, Sisse R. Ostrowski, Anders Koch, Christian Erikstrup, Anne-Marie Vangsted, Anna Irene Vedel Sorensen, Henrik Ullum, Robert Leo Skov, Lone Simonsen, Susanne Dam Nielsen
Summary: This study assessed the burden of long COVID among nonhospitalized adults with PCR-confirmed SARS-CoV-2 infection. The results showed that 25 out of 100 cases reported at least one long-COVID symptom. Infected individuals had worse general health, higher odds of various symptoms, particularly loss of taste and smell, and significantly reduced physical and mental health. Female sex and severity of infection were identified as major risk factors for long COVID.
OPEN FORUM INFECTIOUS DISEASES
(2023)
Article
Microbiology
Kamille Fogh, Alexandra R. R. Eriksen, Tine Graakjaer Larsen, Rasmus B. Hasselbalch, Henning Bundgaard, Bibi F. S. S. Scharff, Susanne D. Nielsen, Charlotte S. Jorgensen, Christian Erikstrup, Lars ostergaard, Svend Ellermann-Eriksen, Berit Andersen, Henrik Nielsen, Isik S. Johansen, Lothar Wiese, Lotte Hindhede, Susan Mikkelsen, Susanne G. Saekmose, Bitten Aagaard, Dorte K. Holm, Lene Harritshoj, Lone Simonsen, Thea K. Fischer, Fredrik Folke, Freddy Lippert, Sisse R. Ostrowski, Thomas Benfield, Kare Molbak, Steen Ethelberg, Anders Koch, Anne-Marie Vangsted, Tyra Grove Krause, Anders Fomsgaard, Henrik Ullum, Robert Skov, Kasper Iversen
Summary: This study investigated the immunity against COVID-19, risk factors, and behavior among employees in day care facilities and preschools (DCS) in Denmark. The study found that DCS staff had a higher risk of exposure within their own household than at their workplace. The study also found that most employees expressed fear of contracting COVID-19 and there was limited use of personal protective equipment at work.
MICROBIOLOGY SPECTRUM
(2023)
Article
Endocrinology & Metabolism
Anton Lund Andersen, Sigrid Bjerge Gribsholt, Lars Pedersen, Reimar Wernich Thomsen, Thomas Lars Benfield, Ole Sogaard, Stig Lonberg Nielsen, Lars Haukali Omland, Birgitte Lindegaard, Bjorn Richelsen, Jacob Bodilsen, Jens Meldgaard Bruun
Summary: This study examines the association between obesity and severity of infection in a Danish cohort hospitalized with COVID-19. The results show that compared to non-obese patients, obese patients have a slightly increased risk of ICU admission, invasive mechanical ventilation, and death, although these relationships are not statistically significant. In addition, COVID-19 patients who are both obese and under the age of 60 have an almost doubled risk of ICU admission and invasive mechanical ventilation.
OBESITY SCIENCE & PRACTICE
(2023)
Article
Biochemistry & Molecular Biology
Xianglei Yan, Sebastian Ols, Rodrigo Arcoverde Cerveira, Klara Lenart, Fredrika Hellgren, Kewei Ye, Alberto Cagigi, Marcus Buggert, Falk Nimmerjahn, Jesper Falkesgaard Hojen, Daniel Parera, Ulrich Pessara, Stephan Fischer, Karin Lore
Summary: Targeting CD40 with agonistic antibodies can stimulate immune responses and be used as vaccine adjuvants or for cancer immunotherapy. A specific agonistic anti-human CD40 monoclonal IgG1 antibody (MAB273) lacking Fc gamma-receptor binding was introduced. MAB273 rapidly bound to B cells and dendritic cells, resulting in activation in vitro and in vivo. It enhanced antigen-specific T cell responses and could be a promising immunostimulatory adjuvant for therapeutic and prophylactic vaccination strategies.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Medicine, Research & Experimental
Maria Lange Pedersen, Dennis Vestergaard Pedersen, Mikael Becher Lykkegaard Winkler, Heidi Gytz Olesen, Ole Schmeltz Sogaard, Lars Ostergaard, Nick Stub Laursen, Anna Halling Folkmar Rahimic, Martin Tolstrup
Summary: The complement system, an important part of the innate immune response, can be utilized to eliminate HIV-1-infected cells. Researchers developed a new therapeutic approach, a bispecific complement engager (BiCE), which can direct complement activity to the surface of HIV-1-infected cells. This BiCE has shown the ability to increase complement deposition and mediate complement-dependent cytotoxicity (CDC) of HIV-1-infected cells.
EMBO MOLECULAR MEDICINE
(2023)
Article
Infectious Diseases
Caecilie Leding, Jacob Bodilsen, Christian Brieghel, Zitta Barrella Harboe, Marie Helleberg, Claire Holm, Simone Bastrup Israelsen, Janne Jensen, Tomas Ostergaard Jensen, Isik Somuncu Johansen, Stine Johnsen, Ole Kirk, Birgitte Lindegaard, Christian Niels Meyer, Rajesh Mohey, Lars Pedersen, Henrik Nielsen, Stig Lonberg Nielsen, Lars Haukali Omland, Daria Podlekareva, Pernille Ravn, Jonathan Starling, Merete Storgaard, Christian Soborg, Ole Schmeltz Sogaard, Torben Tranborg, Lothar Wiese, Signe Heide Westring Worm, Hanne Rolighed Christensen, Thomas Benfield
Summary: This nationwide retrospective cohort study found that COVID-19 hospitalized patients treated with remdesivir and dexamethasone had a lower risk of progression to invasive mechanical ventilation and 30-day mortality compared to those treated with standard of care alone. The reduced risk of mortality was observed in elderly patients, overweight patients, and patients requiring supplemental oxygen at admission, regardless of sex, comorbidities, and symptom duration.
INFECTIOUS DISEASES
(2023)
Article
Virology
Kristoffer Skaalum Hansen, Sofie Eg Jorgensen, Morten Kelder Skouboe, Jane Agergaard, Berit Schiottz-Christensen, Line Khalidan Vibholm, Martin Tolstrup, Lars Ostergaard, Steffen Leth, Trine H. Mogensen
Summary: Long COVID is an emerging global health concern, and its underlying mechanism and pathophysiology are still unclear. This study found that autoantibodies against type 1 interferons in patients with Long COVID do not contribute to the symptoms.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jesper D. Gunst, Jesper F. Hojen, Marie H. Pahus, Miriam Rosas-Umbert, Birgitte Stiksrud, James H. Mcmahon, Paul W. Denton, Henrik Nielsen, Isik S. Johansen, Thomas Benfield, Steffen Leth, Jan Gerstoft, Lars Ostergaard, Mariane H. Schleimann, Rikke Olesen, Henrik Stovring, Line Vibholm, Nina Weis, Anne M. Dyrhol-Riise, Karen B. H. Pedersen, Jillian S. Y. Lau, Dennis C. Copertino, Noemi Linden, Tan T. Huynh, Victor Ramos, R. Brad Jones, Sharon R. Lewin, Martin Tolstrup, Thomas A. Rasmussen, Michel C. Nussenzweig, Marina Caskey, Dag Henrik Reikvam, Ole S. Sogaard
Summary: In people with HIV-1 undergoing antiretroviral treatment interruption, combining lefitolimod with broadly neutralizing antibodies (bNAbs) did not delay viral rebound beyond that achieved with bNAbs alone, raising the question of how to optimize combination immunotherapy to control HIV-1.
Article
Medicine, Research & Experimental
Lisa Lokso Dietz, Anna Karina Juhl, Ole Schmeltz Sogaard, Joanne Reekie, Henrik Nielsen, Isik Somuncu Johansen, Thomas Benfield, Lothar Wiese, Nina Breinholt Staerke, Tomas Ostergaard Jensen, Stine Finne Jakobsen, Rikke Olesen, Kasper Iversen, Kamille Fogh, Jacob Bodilsen, Kristine Toft Petersen, Lykke Larsen, Lone Wulff Madsen, Susan Olaf Lindvig, Inge Kristine Holden, Dorthe Raben, Sidsel Dahl Andersen, Astrid Korning Hvidt, Signe Rode Andreasen, Eva Anna Marianne Baerends, Jens Lundgren, Lars Ostergaard, Martin Tolstrup
Summary: This study examines the immune response to SARS-CoV-2 vaccination in older Danish citizens and finds that age and disease burden can impact the vaccine-induced T cell immunity. These findings contribute to the understanding of immune responses in individuals at increased risk of severe COVID-19.
COMMUNICATIONS MEDICINE
(2023)
Article
Immunology
Astrid Korning Hvidt, Huaijian Guo, Rebecca Andersen, Stine Sofie Frank Lende, Line Khalidan Vibholm, Ole Schmeltz Sogaard, Marianne Hoegsbjerg Schleimann, Victoria Russell, Angela Man-Wei Cheung, Eustache Paramithiotis, Rikke Olesen, Martin Tolstrup
Summary: The study on long-term immune response to SARS-CoV-2 infection in 93 recovered individuals found that a majority maintained stable immune responses 20 months after infection, especially in T cell responses. Vaccination boosted Spike-specific immune responses, indicating understanding of immune contraction and durability of protection.