Review
Oncology
Myriam Ben Khelil, Yann Godet, Syrine Abdeljaoued, Christophe Borg, Olivier Adotevi, Romain Loyon
Summary: CD4(+) T cells play a crucial role in antitumor immunity, either by promoting or suppressing cytotoxic T cell responses. This review highlights the role of CD4(+) T subsets within the tumor microenvironment and discusses the latest developments in modulating CD4(+) T responses for cancer immunotherapy and improving cancer strategies.
Article
Immunology
Kamal El Bissati, Paulette A. Krishack, Ying Zhou, Christopher R. Weber, Joseph Lykins, Dragana Jankovic, Karen L. Edelblum, Laura Fraczek, Harshita Grover, Aziz A. Chentoufi, Gurminder Singh, Catherine Reardon, J. P. Dubey, Steve Reed, Jeff Alexander, John Sidney, Alessandro Sette, Nilabh Shastri, Rima Mcleod
Summary: CD4(+) T cells play critical roles in controlling Toxoplasma infection. The combination of AS15 and GLA-SE can protect mice against Toxoplasma parasites, but can also cause severe pathology. The introduction of PADRE reverses the harmful effects of AS15.
Article
Virology
Jacob K. Files, Sarah Sterrett, Sebastian Henostroza, Christopher Fucile, Kevin Maroney, Tim Fram, Simon Mallal, Spyros Kalams, Jonathan Carlson, Alexander Rosenberg, Nathan Erdmann, Anju Bansal, Paul A. Goepfert
Summary: HLA-II-associated viral adaptation reduces CD4(+) T-cell responses in HIV-1 vaccine recipients, potentially affecting HIV-specific antibody production and vaccine efficacy.
JOURNAL OF VIROLOGY
(2022)
Article
Immunology
Xiao-Peng Dai, Feng-Ying Wu, Cheng Cui, Xue-Jiao Liao, Yan-Mei Jiao, Chao Zhang, Jin-Wen Song, Xing Fan, Ji-Yuan Zhang, Qing He, Fu-Sheng Wang
Summary: Platelet-T cell aggregates play a critical role in maintaining inflammation in chronic HIV-1 infection. The formation of platelet-CD4(+) T cell aggregates was increased in treatment-naive HIV-1-infected individuals compared to healthy controls. Higher levels of these aggregates were associated with HIV-1 permissiveness and immune activation during HIV-1 infection.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Noemia S. Lima, Damee Moon, Samuel Darko, Rafael A. De La Barrera, Leyi Lin, Michael A. Koren, Richard G. Jarman, Kenneth H. Eckels, Stephen J. Thomas, Nelson L. Michael, Kayvon Modjarrad, Daniel C. Douek, Lydie Trautmann
Summary: The study found that prior immunization with JEV has a positive impact on CD4 T cell responses to the ZPIV vaccine, generating more durable responses primarily directed towards conserved epitopes. T cell receptor repertoire analysis revealed preferential expansion of cross-reactive clonotypes between JEV and ZIKV.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Laura Amaya, Lilit Grigoryan, Zhijian Li, Audrey Lee, Paul A. Wender, Bali Pulendran, Howard Y. Chang
Summary: Circular RNAs (circRNAs) are highly stable RNAs that can be engineered to provide durable protein expression. This study shows that circRNA encoding antigenic protein sequences delivered by a charge-altering releasable transporter can serve as both an adjuvant and an immunogen, inducing potent cellular immunity and leading to tumor clearance as a therapeutic vaccine. These results suggest the potential utility of engineered circRNAs for the development of vaccines and therapeutics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Immunology
Yusuf Dolen, Uzi Gileadi, Ji-Li Chen, Michael Valente, Jeroen H. A. Creemers, Eric A. W. Van Dinther, N. Koen van Riessen, Eliezer Jager, Martin Hruby, Vincenzo Cerundolo, Mustafa Diken, Carl G. Figdor, I. Jolanda M. de Vries
Summary: A PLGA-based nanoparticle vaccine containing immunogenic cancer germline antigen NY-ESO-1 and iNKT cell agonist was developed, which efficiently induced antigen-specific T cell responses in vivo without systemic toxicity at high doses.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Kunal Dhume, Brandon Kaye, K. Kai McKinstry
Summary: CD4 T cells have both positive and negative impacts in infectious disease, cancer, autoimmunity, and allergy. They can differentiate into distinct effector subsets with specialized functions. Eomesodermin (Eomes) is an important transcription factor that may be targeted to improve clinical outcomes in CD4 T cell responses.
Article
Immunology
Lorenzo Federico, Tor Henrik Anderson Tvedt, Murat Gainullin, Julie Rokke Osen, Viktoriia Chaban, Katrine Persgard Lund, Lisa Tietze, Trung The Tran, Fridtjof Lund-Johansen, Hassen Kared, Andreas Lind, John Torgils Vaage, Richard Stratford, Simen Tennoe, Brandon Malone, Trevor Clancy, Anders Eivind Leren Myhre, Tobias Gedde-Dahl, Ludvig Andre Munthe
Summary: This study examined the relationship between humoral and T cell response in 48 HSCT recipients who received two doses of Moderna's mRNA-1273 or Pfizer/BioNTech's BNT162b2 vaccines. The results showed that nearly all HSCT patients had robust T cell immunity regardless of protective humoral responses. The data suggests that HSCT recipients with poor serological responses were protected from severe COVID-19 by vaccine-induced T cell responses.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Ying Waeckerle-Men, Zuzanna K. Kotkowska, Geraldine Bono, Agathe Duda, Isabel Kolm, Eleni M. Varypataki, Beat Amstutz, Michael Meuli, Anders Hogset, Thomas M. Kuendig, Cornelia Halin, Peter Sander, Pal Johansen
Summary: This study demonstrates the use of photochemical internalization (PCI) to improve the immunogenicity of live bacterial vaccines. By combining a photosensitizer with Mycobacterium bovis BCG and activating it with light, stronger CD4 and CD8 T-cell responses were induced. This approach also facilitated antigen presentation and caused local inflammation, enhancing the stimulation of antigen-specific immune responses.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Constance Renault, Nicolas Veyrenche, Franck Mennechet, Anne-Sophie Bedin, Jean-Pierre Routy, Philippe Van de Perre, Jacques Reynes, Edouard Tuaillon
Summary: Th17 cells play a crucial role in defending against pathogens at mucosal barriers, but they are also vulnerable to HIV-1 infection and depletion from gut mucosal sites. The imbalance caused by the loss of Th17 cells impairs cytokine production and leads to damage in the gut mucosal barrier, promoting HIV-1 disease progression. The expression of specific receptors by Th17 cells contributes to their susceptibility to HIV infection. Moreover, Th17 cells serve as long-lived viral reservoirs in HIV patients receiving antiretroviral therapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Isabela de Andrade Ferraz, Ana Maria Ravena Severino Carvalho, Rory Cristiane Fortes de Brito, Bruno Mendes Roatt, Vivian Tamietti Martins, Daniela Pagliara Lage, Luiza dos Reis Cruz, Fernanda Alvarenga Cardoso Medeiros, Denise Utsch Goncalves, Manoel Otavio da Costa Rocha, Eduardo Antonio Ferraz Coelho, Tiago Antonio de Oliveira Mendes, Mariana Costa Duarte, Daniel Menezes-Souza
Summary: A gene encoding a chimeric protein with multiple T-cell epitopes was developed as a potential vaccine for tegumentary leishmaniasis. Vaccinated mice showed an increased production of key immunological biomarkers associated with protection against TL and a reduction in cells associated with TL. The vaccine also induced the development of memory T-cells and led to lower parasite burdens.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2022)
Article
Materials Science, Multidisciplinary
Brianna L. Scotland, Andrea L. Cottingham, Jackline Joy M. Lasola, Stephen W. Hoag, Ryan M. Pearson
Summary: In this study, bioconjugate nanoparticles composed of poly(lactic-co-glycolic acid) and ovalbumin were developed to investigate the modulation of immune cell responses. The results showed that the antigen loading and formulation parameters of the nanoparticles played a crucial role in determining the T cell activation and differentiation. This work provides important insights for the design of nanoparticle-based immunotherapies.
ACS APPLIED POLYMER MATERIALS
(2023)
Article
Microbiology
Federica Zavaglio, Irene Cassaniti, Jose Camilla Sammartino, Stelvio Tonello, Pier Paolo Sainaghi, Viola Novelli, Federica Meloni, Daniele Lilleri, Fausto Baldanti
Summary: By comparing the development and persistence of antibody and T-cell responses, we found that the mRNA BNT162b2 vaccine and SARS-CoV-2 infection can induce strong immune responses. Vaccinated subjects and patients with pneumonia had higher levels of antibodies and T-cell responses, while mild COVID-19 patients had weaker immune responses. The antibody response declined over time in vaccinated subjects but could be restored with a booster dose, while the proliferative CD4(+) T-cell response persisted.
Article
Oncology
Michael C. Brown, Georgia M. Beasley, Zachary P. McKay, Yuanfan Yang, Annick Desjardins, Dina M. Randazzo, Daniel Landi, David M. Ashley, Darell D. Bigner, Smita K. Nair, Matthias Gromeier
Summary: This study reveals the contribution of pre-existing anti-polio immunity to the effectiveness of polio virotherapy for cancer treatment. Childhood vaccines such as polio and tetanus can enhance antitumor immune responses, particularly by activating CD4(+) T cells and eosinophils.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Immunology
Jorge A. Masso-Silva, Alexander Moshensky, Michael T. Y. Lam, Mazen F. Odish, Arjun Patel, Le Xu, Emily Hansen, Samantha Trescott, Celina Nguyen, Roy Kim, Katherine Perofsky, Samantha Perera, Lauren Ma, Josephine Pham, Mark Rolfsen, Jarod Olay, John Shin, Jennifer M. Dan, Robert K. Abbott, Sydney Ramirez, Thomas H. Alexander, Grace Y. Lin, Ana Lucia Fuentes, Ira Advani, Deepti Gunge, Victor Pretorius, Atul Malhotra, Xin Sun, Jason Duran, Mark Hepokoski, Shane Crotty, Nicole G. Coufal, Angela Meier, Laura E. Crotty Alexander
Summary: Recent research indicates that COVID-19 patients exhibit increased neutrophil levels in both blood and lung tissue, with activated neutrophils correlating with disease severity. Neutrophils in COVID-19 patients show functional changes, including enhanced neutrophil extracellular trap formation, phagocytosis, and oxidative burst, suggesting a more aggressive antimicrobial and proinflammatory response.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Alison Tarke, Camila H. Coelho, Zeli Zhang, Jennifer M. Dan, Esther Dawen Yu, Nils Methot, Nathaniel Bloom, Benjamin Goodwin, Elizabeth Phillips, Simon Mallal, John Sidney, Gilberto Filaci, Daniela Weiskopf, Ricardo da Silva Antunes, Shane Crotty, Alba Grifoni, Alessandro Sette
Summary: T cell responses induced by different vaccine platforms cross-recognize early SARS-CoV-2 variants, while memory B cells and neutralizing antibodies show significant decreases. The majority of memory T cell responses are preserved against variants, with lower recognition of Omicron by memory B cells.
Article
Multidisciplinary Sciences
John E. Bowen, Amin Addetia, Ha Dang, Cameron Stewart, Jack T. Brown, William K. Sharkey, Kaitlin R. Sprouse, Alexandra C. Walls, Ignacio G. Mazzitelli, Jennifer K. Logue, Nicholas M. Franko, Nadine Czudnochowski, Abigail E. Powell, Exequiel Jr Dellota Jr, Kumail Ahmed, Asefa Shariq Ansari, Elisabetta Cameroni, Andrea Gori, Alessandra Bandera, Christine M. Posavad, Jennifer M. Dan, Zeli Zhang, Daniela Weiskopf, Alessandro Sette, Shane Crotty, Najeeha Talat Iqbal, Davide Corti, Jorge Geffner, Gyorgy Snell, Renata Grifantini, Helen Y. Chu, David Veesler
Summary: The Omicron variant of concern, characterized by numerous spike mutations, exhibits enhanced binding to ACE2, reduced fusogenicity, and reduced neutralizing activity against plasma induced by infection or vaccines. However, booster doses based on the Wuhan-Hu-1 spike sequence significantly increase neutralizing antibody titers and breadth against multiple Omicron sublineages.
Article
Cell Biology
Wan-Ting He, Meng Yuan, Sean Callaghan, Rami Musharrafieh, Ge Song, Murillo Silva, Nathan Beutler, Wen-Hsin Lee, Peter Yong, Jonathan L. Torres, Mariane Melo, Panpan Zhou, Fangzhu Zhao, Xueyong Zhu, Linghang Peng, Deli Huang, Fabio Anzanello, James Ricketts, Mara Parren, Elijah Garcia, Melissa Ferguson, William Rinaldi, Stephen A. Rawlings, David Nemazee, Davey M. Smith, Bryan Briney, Yana Safonova, Thomas F. Rogers, Jennifer M. Dan, Zeli Zhang, Daniela Weiskopf, Alessandro Sette, Shane Crotty, Darrell J. Irvine, Andrew B. Ward, Ian A. Wilson, Dennis R. Burton, Raiees Andrabi
Summary: Immunization of macaques with SARS-CoV-2 spike protein generated potent cross-neutralizing antibody responses, effective against both SARS-CoV-2 and SARS-CoV-1, as well as most SARS-CoV-2 variants.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Immunology
Simon Belanger, Sonya Haupt, Brian L. Freeman, Adam J. Getzler, Huitian Diao, Matthew E. Pipkin, Shane Crotty
Summary: The study revealed that Yin Yang 1 (YY-1) is a novel positive regulator involved in the differentiation of TFH cells. The absence of YY-1 significantly impairs TFH differentiation, leading to compromised immune system function.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Jennifer M. Dan, Susan M. Lehman, Rita Al-kolla, Samuel Penziner, Kamyar Afshar, Gordon Yung, Eugene Golts, Nancy Law, Cathy Logan, Zsuzsanna Kovach, Gill Mearns, Robert T. Schooley, Saima Aslam, Shane Crotty
Summary: Bacteriophage therapy involves using viruses to kill antibiotic-resistant bacteria. In this case study, we observed the development of phage-specific CD4 T cells, immunoglobulin G, and neutralizing antibodies in response to bacteriophage therapy for a lung transplant recipient with multidrug-resistant Pseudomonas aeruginosa pneumonia. Despite the development of phage-specific immune responses, the treatment was considered successful. We provide a detailed profile of the immune responses in this case.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Multidisciplinary Sciences
Jeong Hyun Lee, Henry J. Sutton, Christopher A. Cottrell, Ivy Phung, Gabriel Ozorowski, Leigh M. Sewall, Rebecca Nedellec, Catherine Nakao, Murillo Silva, Sara T. Richey, Jonathan L. Torre, Wen-Hsin Lee, Erik Georgeson, Michael Kubitz, Sam Hodges, Tina-Marie Mullen, Yumiko Adachi, Kimberly M. Cirelli, Amitinder Kaur, Carolina Allers, Marissa Fahlberg, Brooke F. Grasperge, Jason P. Dufour, Faith Schiro, Pyone P. Aye, Oleksandr Kalyuzhniy, Alessia Liguori, Diane G. Carnathan, Guido Silvestri, Xiaoying Shen, David C. Montefiori, Ronald S. Veazey, Andrew B. Ward, Lars Hangartner, Dennis R. Burton, Darrell J. Irvine, William R. Schief, Shane Crotty
Summary: This study demonstrates the presence of long-lasting germinal centre B cells in rhesus monkeys after a long period of immunization without further exposure to antigens. The B cells generated under these conditions show higher levels of antibody somatic hypermutation and are more likely to recognize non-immunodominant epitopes. The findings suggest that a long-prime, slow-delivery immunization approach holds promise for difficult vaccine targets.
Article
Microbiology
Mohammad M. Sajadi, Amber Myers, James Logue, Saman Saadat, Narjes Shokatpour, James Quinn, Michelle Newman, Meagan Deming, Zahra Rikhtegaran Tehrani, Laurence S. Magder, Maryam Karimi, Abdolrahim Abbasi, Mike Shlyak, Lauren Baracco, Matthew B. Frieman, Shane Crotty, Anthony D. Harris
Summary: Understanding the immune responses to the SARS-CoV-2 spike protein is crucial in controlling the COVID-19 pandemic. This study examines the responses to SARS-CoV-2 mRNA vaccines in individuals with and without prior infection, revealing that the severity of infection impacts the IgA responses in primary infection and vaccination response (peak responses and durability), which has implications for protection against reinfection.
Article
Multidisciplinary Sciences
Peifang Sun, Irene Ramos, Camila H. Coelho, Alba Grifoni, Corey A. Balinsky, Sindhu Vangeti, Alison Tarke, Nathaniel I. Bloom, Vihasi Jani, Silvia J. Jakubski, David A. Boulifard, Elizabeth Cooper, Carl W. Goforth, Jan Marayag, Amethyst Marrone, Edgar Nunez, Lindsey White, Chad K. Porter, Victor A. Sugiharto, Megan Schilling, S. Avinash, S. Mahajan, Charmagne Beckett, Alessandro Sette, Stuart C. Sealfon, Shane Crotty, Andrew G. Letizia
Summary: This cross-sectional study examined the immune responses of 18-21-year-old Marines who had previously been infected with SARS-CoV-2, including the Omicron variant. The results showed that vaccination significantly enhanced the immune responses of previously infected individuals, including the recognition of Omicron, compared to those who were infected but not vaccinated. Additionally, there were no significant differences in immune memory for ancestral or variant strains among young adults with previous symptomatic or asymptomatic infections.
Correction
Multidisciplinary Sciences
Jeong Hyun Lee, Henry J. J. Sutton, Christopher A. A. Cottrell, Ivy Phung, Gabriel Ozorowski, Leigh M. M. Sewall, Rebecca Nedellec, Catherine Nakao, Murillo Silva, Sara T. T. Richey, Jonathan L. L. Torres, Wen-Hsin Lee, Erik Georgeson, Michael Kubitz, Sam Hodges, Tina-Marie Mullen, Yumiko Adachi, Kimberly M. M. Cirelli, Amitinder Kaur, Carolina Allers, Marissa Fahlberg, Brooke F. F. Grasperge, Jason P. P. Dufour, Faith Schiro, Pyone P. P. Aye, Oleksandr Kalyuzhniy, Alessia Liguori, Diane G. G. Carnathan, Guido Silvestri, Xiaoying Shen, David C. C. Montefiori, Ronald S. S. Veazey, Andrew B. B. Ward, Lars Hangartner, Dennis R. R. Burton, Darrell J. J. Irvine, William R. R. Schief, Shane Crotty
Correction
Immunology
Amy C. Palin, Galit Alter, Shane Crotty, Ali H. Ellebedy, M. Chelsea Lane, F. Eun-Hyung Lee, Michela Locci, Angela Malaspina, Conrad Mallia, M. Juliana McElrath, Bali Pulendran, Anjali Singh, M. Patricia D'Souza
Meeting Abstract
Immunology
Alba Grifoni, Alison Tarke, Jennifer Dan, Camila Coelho, Zeli Zhang, Daniela Weiskopf, Ricardo Da Silva Antunes, Shane Crotty
JOURNAL OF IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Carolyn Rydyznski Moderbacher, Christina Kim, Jose Mateus, Joyce Plested, Mingzhu Zhu, Shane Cloney-Clark, Daniela Weiskopf, Alessandro Sette, Louis Fries, Gregory Glenn, Shane Crotty
Summary: NVX-CoV2373 vaccine induces CD4(+) and CD8+ T cell responses, and the production of CD4(+) T cells is correlated with the generation of neutralizing antibodies. This suggests that robust CD4(+) T cell generation may be a key characteristic of NVX-CoV2373 in supporting humoral immune responses.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Immunology
Jennifer M. Dan, Susan M. Lehman, Rita Al-Kolla, Samuel Penziner, Kamyar Afshar, Gordon Yung, Eugene Golts, Nancy Law, Cathy Logan, Zsuzsanna Kovach, Gill Mearns, Robert T. Schooley, Saima Aslam, Shane Crotty
Summary: This study reported a case of successful treatment of multidrug-resistant Pseudomonas aeruginosa pneumonia in a lung transplant recipient using phage therapy. The development of phage-specific immune response was observed.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Multidisciplinary Sciences
Aleksandar Antanasijevic, Charles A. Bowman, Robert N. Kirchdoerfer, Christopher A. Cottrell, Gabriel Ozorowski, Amit A. Upadhyay, Kimberly M. Cirelli, Diane G. Carnathan, Chiamaka A. Enemuo, Leigh M. Sewall, Bartek Nogal, Fangzhu Zhao, Bettina Groschel, William R. Schief, Devin Sok, Guido Silvestri, Shane Crotty, Steven E. Bosinger, Andrew B. Ward
Summary: A hybrid approach combining structural and bioinformatic methods is presented for the identification and synthesis of monoclonal antibodies from serum-derived polyclonal antibodies, allowing for analysis of immune responses and iterative vaccine design.