Article
Immunology
Sabrina Helmold Hait, Christopher James Hogge, Mohammad Arif Rahman, Ruth Hunegnaw, Zuena Mushtaq, Tanya Hoang, Marjorie Robert-Guroff
Summary: T follicular helper (T-FH) cells play a crucial role in B cell affinity maturation in lymph nodes. Meanwhile, circulating CXCR5(+) CD4(+) T (cT(FH)) cells support memory B cell activation and broadly neutralizing antibodies in HIV controllers. This study investigated the contribution of LN SIV-specific T-FH and cT(FH) cells to Env-specific humoral immunity in female rhesus macaques under different vaccination and SIV challenge conditions, revealing the importance of T-FH responses in blood and secondary lymphoid organs for protective efficacy of HIV vaccines.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Justin Harper, Nicolas Huot, Luca Micci, Gregory Tharp, Colin King, Philippe Rascle, Neeta Shenvi, Hong Wang, Cristin Galardi, Amit A. Upadhyay, Francois Villinger, Jeffrey Lifson, Guido Silvestri, Kirk Easley, Beatrice Jacquelin, Steven Bosinger, Michaela Muller-Trutwin, Mirko Paiardini
Summary: The study demonstrated that sequential interleukin-21 and interferon alpha therapy can generate terminally differentiated natural killer cells with potent activity in SIV-infected rhesus macaques, reducing SIV dissemination in lymph nodes. This suggests that the differentiation profiles of natural killer cells seen in African green monkeys can be rescued in rhesus macaques to promote viral clearance in tissues.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Siqi Liu, Lanlan Yang, Shengnan Jia, Rui Zhao, Zhenjing Jin
Summary: In patients with hepatocellular carcinoma (HCC), the levels of NKB cells and IL-18 secretion were decreased in both peripheral blood and liver-infiltrating sites. Elevated IL-35 levels were negatively correlated with the percentage of NKB cells and IL-18 production in HCC, suggesting a suppressive role of IL-35 on NKB cell activity.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Immunology
Brianna C. Davey, Mary S. Pampusch, Emily K. Cartwright, Hadia M. Abdelaal, Eva G. Rakasz, Aaron Rendahl, Edward A. Berger, Pamela J. Skinner
Summary: T cells expressing a SIV-specific chimeric antigen receptor (CAR) and CXCR5 were infused into SIV-infected rhesus macaques on antiretroviral therapy (ART) to assess their ability to control the virus. These cells showed evidence of functionality but failed to persist in the animals beyond 28 days, possibly due to the development of anti-CAR antibodies. The study suggests that the CD4 and CD28 domains of the CAR are immunogenic and could impact the long-term persistence of CAR immunotherapies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Victoria E. K. Walker-Sperling, Noe B. Mercado, Abishek Chandrashekar, Erica N. Borducchi, Jinyan Liu, Joseph P. Nkolola, Mark Lewis, Jeffrey P. Murry, Yunling Yang, Romas Geleziunas, Merlin L. Robb, Nelson L. Michael, Maria G. Pau, Frank Wegmann, Hanneke Schuitemaker, Emily J. Fray, Mithra R. Kumar, Janet D. Siliciano, Robert F. Siliciano, Dan H. Barouch
Summary: This study suggests that combining active and passive immunization may have the potential in curing HIV-1. In SHIV-infected rhesus macaques, a combination of therapeutic vaccination and antibody administration with vesatolimod resulted in 70% post-ART virologic control.
NATURE COMMUNICATIONS
(2022)
Article
Virology
Siva Thirugnanam, Edith M. Walker, Faith Schiro, Pyone P. Aye, Jay Rappaport, Namita Rout
Summary: Previous studies have shown that the loss of CD161-expressing CD4(+) Th17 cells is associated with the progression of chronic HIV infection. These cells are significantly reduced in the peripheral blood and gut mucosa of HIV-infected individuals, leading to inflammation and disruption of the gut barrier. However, the impact of HIV infection on CD161-expressing CD8(+) T cells is still unclear.
Article
Multidisciplinary Sciences
Vijayakumar Velu, Kehmia Titanji, Hasan Ahmed, Ravi Dyavar Shetty, Lakshmi S. Chennareddi, Gordon J. Freeman, Rafi Ahmed, Rama Rao Amara
Summary: The study demonstrated that PD-1 blockade following ART interruption significantly enhances the function of anti-viral CD8 T cells and improves viral control. It suggests the potential synergistic effects of PD-1 blockade with other immunotherapies inducing functional CD8 T-cell responses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Mary S. Pampusch, Emily N. Sevcik, Zoe E. Quinn, Brianna C. Davey, James M. Berg, Ian Gorrell-Brown, Hadia M. Abdelaal, Eva G. Rakasz, Aaron Rendahl, Pamela J. Skinner
Summary: This study found that SIV-infected rhesus macaques treated with CXCR5-expressing SIV-specific CD4-MBL-CAR-T cells showed reduced viral loads. The temporary disruption of lymphoid follicles increased the abundance and persistence of CAR-T cells. These findings have important implications for the development of cellular immunotherapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Arshi Khanam, Natarajan Ayithan, Lydia Tang, Bhawna Poonia, Shyam Kottilil
Summary: Chronic Hepatitis B affects over 350 million people worldwide, and current treatments do reduce complications but do not provide a cure. Humoral responses in CHB rely on T-FH cells to support B cell response, with IL-21 playing a key role. However, defective T-FH cells in CHB can efficiently support B cell responses by producing IL-27, which aids in viral clearance and improving antibody production.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Sanghita Sarkar, David A. Spencer, Philip Barnette, Shilpi Pandey, William F. Sutton, Madhubanti Basu, Reuben E. Burch, John D. Cleveland, Alexander F. Rosenberg, Javier Rangel-Moreno, Michael C. Keefer, Ann J. Hessell, Nancy L. Haigwood, James J. Kobie
Summary: The study found that HIV neutralizing antibodies were still generated even in the absence of CD4+ T cell help, and the effectiveness of HIV vaccine may still exist in the presence of diminished CD4+ T cell help.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Evan S. Walsh, Tammy S. Tollison, Hayden N. Brochu, Brian Shaw, Kayleigh R. Diveley, Hsuan Chou, Lynn Law, Allan D. Kirk, Michael Gale, Xinxia Peng
Summary: Recent advancements in microfluidics and high-throughput sequencing technologies have made it possible to analyze the immune repertoire of rhesus macaques at the single-cell level. Custom primers and a commercial solution were used to sequence the Ig and TCR repertoires, allowing for the recovery of every antibody isotype and TCR chain. The study also measured clonal expansion in T cells and paired the immune repertoire with gene expression profiles.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Microbiology
Roslyn A. Taylor, Michael D. McRaven, Ann M. Carias, Meegan R. Anderson, Edgar Matias, Mariluz Arainga, Edward J. Allen, Kenneth A. Rogers, Sandeep Gupta, Viraj Kulkarni, Samir Lakhashe, Ramon Lorenzo-Redondo, Yanique Thomas, Amanda Strickland, Francois J. Villinger, Ruth M. Ruprecht, Thomas J. Hope
Summary: The study showed that HIV rapidly spread and penetrated the entire gastrointestinal tract in neonatal rhesus macaques as early as four hours after oral viral challenge, with the largest number of infected cells found in the small and large intestine at 96 hours, predominantly T cells. These findings highlight the importance of understanding viral distribution and infection dynamics in neonates.
Article
Biochemistry & Molecular Biology
Patrick M. McTernan, Robert W. Siggins, Anna Catinis, Angela M. Amedee, Liz Simon, Patricia E. Molina
Summary: Effective antiretroviral therapy has turned HIV into a chronic disease, leading to a growing population of people over 50 living with HIV. Animal experiments have shown that chronic binge alcohol consumption and ovariectomy result in increased expression of SIV co-receptors in peripheral activated CD4(+) T cells and dysregulation of mitochondrial homeostasis.
Article
Immunology
Nongthombam Boby, Xuewei Cao, Alyssa Ransom, Barcley T. Pace, Christopher Mabee, Monica N. Shroyer, Arpita Das, Peter J. Didier, Sudesh K. Srivastav, Edith Porter, Qiuying Sha, Bapi Pahar
Summary: Research has shown that under SIV infection, intestinal epithelial regeneration decreases, certain cell types increase, and differentially expressed genes in important pathways are downregulated. Despite the lack of significant reduction in stem cell population, dysregulation of intestinal stem cell niche factors, presence of inflammatory factors, and loss of epithelial barrier function, suggest that SIV infection impacts epithelial cell proliferation and intestinal homeostasis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Virology
Xinjie Li, Liyan Zhu, Yue Yin, Xueying Fan, Linting Lv, Yuqi Zhang, Yijin Pan, Yangxuanyu Yan, Hua Liang, Jing Xue, Tao Shen
Summary: This study investigates the impact of NK cells on the viral levels of SIV-infected macaques and finds a significant positive correlation between the frequency of NK cells and the ratios of cellular SIV DNA/RNA. However, the limited abundance of NK cells in lymph nodes restricts their cytotoxicity effect on the latent SIV viral load.
Article
Immunology
Violeta J. Rodriguez, John M. Abbamonte, Manasi S. Parrish, Deborah L. Jones, Stephen Weiss, Suresh Pallikkuth, Michal Toborek, Maria L. Alcaide, Dushyantha Jayaweera, Savita Pahwa, Tatjana Rundek, Barry E. Hurwitz, Mahendra Kumar
Summary: The study found that in young to middle-age adults, cocaine use was associated with greater relative cardiovascular risk scores, but biomarkers were not associated with cardiovascular risk. Age and cardiovascular risk scores were related to carotid atherosclerotic plaque, while HIV status did not show any associations with cardiovascular risk scores or carotid atherosclerotic plaque.
INTERNATIONAL JOURNAL OF STD & AIDS
(2022)
Article
Immunology
Daniela Frasca, Suresh Pallikkuth, Savita Pahwa
Summary: Metabolic changes are common signs of aging and can increase the risk of developing age-related diseases. The impact of aging on the metabolic phenotype of immune cells, particularly B cells, is not well understood. However, preliminary research suggests that targeting metabolic pathways could be a potential novel therapeutic approach to reduce inflammaging and enhance humoral immunity.
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
(2022)
Article
Immunology
Suresh Pallikkuth, Savita Pahwa
Summary: Our understanding of HIV/AIDS has undergone a transformation due to the use of novel antiretroviral therapy, allowing clinicians and patients to control the progression of the disease. This supplement presents an overview of the virtual symposium on HIV and Aging in the Era of ART and COVID-19, held on February 8-9, 2021, organized by the Miami Center for AIDS Research, including articles contributed by speakers and members of the organizing committee, as well as presentations by junior investigators.
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
(2022)
Article
Immunology
Stefano Rinaldi, Suresh Pallikkuth, Lesley De Armas, Brian Richardson, Li Pan, Rajendra Pahwa, Sion Williams, Mark Cameron, Savita Pahwa
Summary: This study aimed to identify molecular signatures of aging in HIV-infected individuals compared with age-matched healthy control participants. The researchers found that metabolic and innate immune activation pathways were associated with increasing age in both HIV and healthy control groups. Additionally, age was associated with pathways involved with T-cell immune activation in healthy controls and with interferon signaling pathways in HIV-infected individuals.
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
(2022)
Editorial Material
Immunology
Monty Montano, Alan Landay, Molly Perkins, Marcia Holstad, Suresh Pallikkuth, Savita Pahwa
Summary: Antiretroviral therapy has changed the clinical environment of HIV, resulting in similar common morbidities and causes of death between HIV-infected and noninfected individuals. However, these conditions manifest earlier in people living with HIV, and the emergence of SARSCoV-2 infection has further complicated the accelerated aging process in HIV.
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
(2022)
Article
Immunology
Bagavathi Kausalya, Shanmugam Saravanan, Suresh Pallikkuth, Rajendra Pahwa, Shelly Rani Saini, Syed Iqbal, Sunil Solomon, Kailapuri G. Murugavel, Selvamuthu Poongulali, Nagalingeswaran Kumarasamy, Savita Pahwa
Summary: This study investigated the effects of systemic inflammation, microbial translocation, T cell immune activation, and nadir CD4 counts on cardiac function and arterial stiffness in HIV-infected individuals. The authors found that initiation of antiretroviral therapy (ART) even at low CD4 counts may improve cardiac function and reduce arterial stiffness, and decrease inflammation and microbial translocation. Participants who were not receiving ART were most affected, while those on ART had similar measures to uninfected individuals, even with low CD4 counts.
Article
Immunology
Stanley Kimbung Mbandi, Hannah Painter, Adam Penn-Nicholson, Asma Toefy, Mzwandile Erasmus, Willem A. Hanekom, Thomas J. Scriba, Rachel P. J. Lai, Suzaan Marais, Helen A. Fletcher, Graeme Meintjes, Robert J. Wilkinson, Mark F. Cotton, Savita Pahwa, Mark J. Cameron, Elisa Nemes
Summary: Immune reconstitution inflammatory syndrome (IRIS) is a complication of antiretroviral therapy (ART) in patients with advanced HIV, but its pathogenesis is uncertain. This study found that immune-based blood transcriptomic signatures (RISK6 and Sweeney3) have the potential to predict and diagnose IRIS in HIV+ children and adults.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Stephen Morris, Shweta Anjan, Suresh Pallikkuth, Paola Frattaroli, Steve Courel, Anmary Fernandez, Akina Natori, Lilian Abbo, Savita Pahwa, Giselle Guerra, Yoichiro Natori
Summary: Solid organ transplant recipients infected with SARS-CoV-2 remain at high risk for reinfection even after generating cellular and humoral immune responses.
TRANSPLANT INFECTIOUS DISEASE
(2022)
Article
Immunology
Sara Dominguez-Rodriguez, Alfredo Tagarro, Caroline Foster, Paolo Palma, Nicola Cotugno, Sonia Zicari, Alessandra Ruggiero, Anita de Rossi, Annalisa Dalzini, Savita Pahwa, Stefano Rinaldi, Eleni Nastouli, Anne-Genevieve Marcelin, Karim Dorgham, Delphine Sauce, Kathleen Gartner, Paolo Rossi, Carlo Giaquinto, Pablo Rojo
Summary: This study aimed to assess different subphenotypes in children with HIV-1. Three subphenotypes with different virological and immunological features were identified, with one characterized by a faster immune reconstitution and slower disease progression, while another characterized by more senescent cells and a high reservoir size.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Viviana Simon, Vamsi Kota, Ryan F. Bloomquist, Hannah B. Hanley, David Forgacs, Savita Pahwa, Suresh Pallikkuth, Loren G. Miller, Joanna Schaenman, Michael R. Yeaman, David Manthei, Joshua Wolf, Aditya H. Gaur, Jeremie H. Estepp, Komal Srivastava, Juan Manuel Carreno, Frans Cuevas, Ali H. Ellebedy, Aubree Gordon, Riccardo Valdez, Sarah Cobey, Elaine F. Reed, Ravindra Kolhe, Paul G. Thomas, Stacey Schultz-Cherry, Ted M. Ross, Florian Krammer
Summary: This study provides a detailed description of the PARIS/SPARTA cohorts, harmonized assays, and analysis methods, as well as case definitions for SARS-CoV-2 infection and reinfection. Determining reinfection rates and correlates of protection against SARS-CoV-2 infection induced by both natural infection and vaccination is of high significance for the prevention and control of COVID-19.
Article
Immunology
Katrine Schou Sandgaard, Triantafylia Gkouleli, Teresa Attenborough, Stuart Adams, Deena Gibbons, Mette Holm, Sarah Eisen, Helen Baxendale, Anita De Rossi, Savita Pahwa, Benny Chain, Athina S. Gkazi, Nigel Klein
Summary: Current ART guidelines recommend treating all children with HIV-1 infection to improve morbidity and minimize mortality. This study provides new insights into the unique pediatric immune system and immunological changes when HIV-1 replication is ongoing.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Health Policy & Services
Maria Grazia Lain, Sergio Chicumbe, Anna Cantarutti, Gloria Porcu, Loide Cardoso, Nicola Cotugno, Paolo Palma, Rajendra Pahwa, Suresh Pallikkuth, Stefano Rinaldi, Paula Vaz, Savita Pahwa
Summary: Psychosocial support (PSS) for caregivers of HIV-infected infants is crucial for ART adherence and long-term viral suppression. This study in Mozambique found that the standard PSS approach alone was insufficient in identifying barriers to adherence, highlighting the need for a comprehensive, patient-centered PSS package of care tailored to caregivers and their children.
AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV
(2023)
Article
Infectious Diseases
Catherine K. Koofhethile, Stefano Rinaldi, Yelizaveta Rassadkina, Vinh B. Dinh, Ce Gao, Suresh Pallikkuth, Pilar Garcia-Broncano, Lesley R. de Armas, Rajendra Pahwa, Nicola Cotugno, Paula Vaz, Maria Grazia Lain, Paolo Palma, Xu G. Yu, Roger Shapiro, Savita Pahwa, Mathias Lichterfeld
Summary: This study longitudinally analyzed the proviral landscape in infants with HIV-1 infection and found that early initiation of antiretroviral therapy led to a rapid decline in intact proviruses. The results also suggest that the vulnerability of intact proviruses to antiviral immunity may contribute to their disproportionate under-representation.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Immunology
Erin C. Williams, Alexander Kizhner, Valerie S. Stark, Aria Nawab, Daniel D. Muniz, Felipe Echeverri Tribin, Juan Manuel Carreno, Dominika Bielak, Gagandeep Singh, Michael E. Hoffer, Florian Krammer, Suresh Pallikkuth, Savita Pahwa
Summary: This study used LASSO and linear mixed effects models to evaluate the influence of pre-existing immunity, demographic factors, and vaccine reactogenicity on antibody responses to COVID vaccination. The results showed that previously infected individuals had more durable and robust antibodies after vaccination compared to natural infection alone. Experiencing symptoms during natural infection and post-vaccine were predictive of higher antibody levels. The findings suggest that vaccination in COVID+ individuals can lead to a more robust immune response.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Alessandra Ruggiero, Giuseppe Rubens Pascucci, Nicola Cotugno, Sara Dominguez-Rodriguez, Stefano Rinaldi, Alfredo Tagarro, Pablo Rojo, Caroline Foster, Alasdair Bamford, Anita De Rossi, Eleni Nastouli, Nigel Klein, Elena Morrocchi, Benoit Fatou, Kinga K. Smolen, Al Ozonoff, Michela Di Pastena, Katherine Luzuriaga, Hanno Steen, Carlo Giaquinto, Philip Goulder, Paolo Rossi, Ofer Levy, Savita Pahwa, Paolo Palma
Summary: Children with perinatally acquired HIV (PHIV) exhibit signs of B-cell hyperactivation despite successful antiretroviral therapy (ART), which may result in reduced cell functionality and loss of vaccine-induced immunity. This hyperactivation is associated with proteins involved in immune inflammation and complement activation pathways.
FRONTIERS IN IMMUNOLOGY
(2022)