Article
Microbiology
Hannah M. Schapiro, Mukta D. Khasnis, Koree Ahn, Alexandra Karagiaridi, Stephanie Hayden, Maria E. Cilento, Michael J. Root
Summary: Surface glycoprotein Env of HIV-1 plays a crucial role in viral entry and is a key target for neutralizing antibodies. This study investigated the regulation of the exposure of the gp41 membrane-proximal external region (MPER) by inter- and intra-gp120 interactions mediated by the V1/V2 and V3 loops. The results revealed that swapping V3 loops and altering V3-loop charge had significant effects on antibody access to the MPER epitope and suggested a new structural fluctuation during Env activation.
Article
Virology
Soohyun Kim, Maria V. Filsinger V. Interrante, Peter S. S. Kim
Summary: The trimeric glycoprotein Env on the surface of HIV-1 is the target of broadly neutralizing antibodies and vaccine development efforts. Antibodies that target the membrane proximal external region (MPER) of Env show lipid-binding characteristics and increasing their local concentration through binding to the Fc receptor Fc gamma RI can potentiate their ability to prevent viral entry. This study shows that lipid-binding activity and Fc gamma RI-mediated potentiation work together to improve the potency of MPER-directed antibodies by increasing their local concentration near the site of viral fusion.
JOURNAL OF VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Nuno Taveira, Ines Figueiredo, Rita Calado, Francisco Martin, Ines Bartolo, Jose M. Marcelino, Pedro Borrego, Fernando Cardoso, Helena Barroso
Summary: Developing immunogens that can elicit broadly neutralizing antibodies (bNAbs) is crucial for the development of an effective HIV vaccine. In this study, a prime-boost vaccination strategy using vaccinia virus expressing the gp120 envelope glycoprotein of HIV-2 and a polypeptide comprising specific regions of the envelope glycoprotein was shown to elicit bNAbs against both HIV-1 and HIV-2. The findings suggest that a chimeric envelope glycoprotein containing specific regions from both viruses could be a potential vaccine immunogen to target neutralizing epitopes in both HIV-1 and HIV-2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Jord C. Stam, Steven de Maat, Dorien de Jong, Mathia Arens, Fenna van Lint, Lavina Gharu, Mark H. van Roosmalen, Rob C. Roovers, Nika M. Strokappe, Ralf Wagner, Alexander Kliche, Hans J. de Haard, Paul M. van Bergen en Henegouwen, Monique Nijhuis, C. Theo Verrips
Summary: The researchers propose a novel approach to clear HIV-1 by capturing the virus and redirecting it to non-target cells for internalization and degradation using bispecific antibodies. This method may provide an alternative strategy for treatment.
SCIENTIFIC REPORTS
(2022)
Review
Virology
Emma Parker Miller, Maxwell T. Finkelstein, Molly C. Erdman, Paul C. Seth, Daniela Fera
Summary: Approximately 10-20% of HIV-1 infected individuals develop antibodies that can neutralize diverse HIV-1 strains, which are crucial for vaccine design and therapy. Structural analyses reveal a limited number of vulnerable sites on the HIV-1 spike, providing insights for vaccine design and combination therapy strategies to reduce viral resistance mutations. Recent updates on spike structures in complex with broadly neutralizing antibodies are discussed in the context of all epitopes identified to date.
Article
Virology
David Sacks, Kevin Wiehe, Lynn Morris, Penny L. Moore
Summary: A major focus in the search for an HIV vaccine is understanding the ontogeny of broadly neutralizing antibodies (bNAbs) that can prevent HIV infection. This study investigated the mutations in the CAP256-VRC26 bNAb lineage that confer neutralization capacity to the unmutated common ancestor (CAP256.UCA). The heavy and light chains of the antibody were found to have complementary roles in neutralization breadth and potency, with the heavy chain responsible for conferring breadth. Mutations in previously uninvestigated regions also contributed to breadth. Vaccine approaches that promote affinity maturation at key sites could more rapidly produce antibodies with neutralization breadth.
JOURNAL OF VIROLOGY
(2022)
Article
Microbiology
Wenqi Tang, Zhenzhen Yuan, Zheng Wang, Li Ren, Dan Li, Shuhui Wang, Yanling Hao, Jing Li, Xiuli Shen, Yuhua Ruan, Yiming Shao, Ying Liu
Summary: The MPER of HIV-1 is an attractive vaccine target due to its neutralizing epitopes and conserved amino acids. By studying a patient with neutralizing activity against MPER, it was found that mutations in the MPER significantly decreased the neutralization sensitivity of the virus to autologous plasma.
Article
Immunology
Jeffrey L. Nordstrom, Guido Ferrari, David M. Margolis
Summary: A major strategy to target persistent HIV infection is to induce HIV provirus expression using drugs and then eliminate infected cells through enhanced immune responses. Bispecific antibody molecules can recognize infected cells and recruit immune cells to eliminate them, based on conserved viral epitopes.
JOURNAL OF VIRUS ERADICATION
(2022)
Article
Multidisciplinary Sciences
Larance Ronsard, Ashraf S. Yousif, Faez Amokrane Nait Mohamed, Jared Feldman, Vintus Okonkwo, Caitlin McCarthy, Julia Schnabel, Timothy Caradonna, Ralston M. Barnes, Daniel Rohrer, Nils Lonberg, Aaron Schmidt, Daniel Lingwood
Summary: Low affinity is common for germline B cell receptors (BCR) that develop broadly neutralizing antibodies (bnAbs) against hypervariable viruses like HIV. The non-homogenizing antibody affinity selection ensures the survival of low affinity B cell clones. By using transgenic mice mimicking human antibody diversity and somatic hypermutation (SHM), researchers demonstrate an immunization regimen that focuses B cell memory on the conserved CD4 binding site (CD4bs) through both traditional affinity maturation and the expansion of low affinity BCR clones with shared SHM patterns. This suggests that permissive B cell selection enables the discovery of antibody epitopes, such as an HIV bnAb site.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Rory Henderson, Ye Zhou, Victoria Stalls, Kevin Wiehe, Kevin O. Saunders, Kshitij Wagh, Kara Anasti, Maggie Barr, Robert Parks, S. Munir Alam, Bette Korber, Barton F. Haynes, Alberto Bartesaghi, Priyamvada Acharya
Summary: Antibody affinity maturation plays a crucial role in adaptive immune responses to pathogens. This study focuses on the development of broadly neutralizing antibodies against rapidly mutating pathogens such as HIV-1. By determining the structures of antibodies at different stages of development, the researchers identify key mutations and potential solutions for improving affinity maturation, which can inform the design of effective vaccines.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Simone Conti, Kevin J. Kaczorowski, Ge Song, Katelyn Porter, Raiees Andrabi, Dennis R. Burton, Arup K. Chakraborty, Martin Karplus
Summary: Developing a vaccine that can generate broadly neutralizing antibodies against HIV is crucial in combating the HIV epidemic, but it requires at least three stages. The challenge lies in designing an optimal panel of antigens that can elicit such antibodies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Simone Conti, Kevin J. Kaczorowski, Ge Song, Katelyn Porter, Raiees Andrabi, Dennis R. Burton, Arup K. Chakraborty, Martin Karplus
Summary: Research has shown that a vaccine capable of eliciting broadly neutralizing antibodies against HIV has potential to protect against the virus, involving at least three separate stages. This vaccine may require immunization with a mixture of Envs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Gabriel Siracusano, Lucia Lopalco
Summary: Full HIV-1 remission has not been achieved since its discovery 35 years ago. Combined antiretroviral therapy (cART) can control viral replication, but is unable to eradicate latent reservoirs and may lead to side effects. Antibody-based treatments, such as anti-CCR5 antibodies, have emerged as alternative approaches to target early stages of infection.
Article
Virology
Daniel J. Sheward, Tandile Hermanus, Ben Murrell, Nigel Garrett, Salim S. Abdool Karim, Lynn Morris, Penny L. Moore, Carolyn Williamson
Summary: The development of broadly neutralizing antibodies (bNAbs) to HIV and other diverse pathogens may require the use of multiple immunogens. This study characterizes the antibody responses in individuals coinfected with multiple HIV variants, revealing interference and the potential role of conserved neutralizing epitopes in guiding broad antibody responses.
JOURNAL OF VIROLOGY
(2022)
Article
Biology
Christophe Caillat, Delphine Guilligay, Johana Torralba, Nikolas Friedrich, Jose L. Nieva, Alexandra Trkola, Christophe J. Chipot, Francois L. Dehez, Winfried Weissenhorn
Summary: The study presents the crystal structure of HIV-1 gp41 locked in a fusion intermediate state by a neutralizing antibody, showing the structural plasticity and conformational flexibility of membrane anchors. Molecular dynamics simulation suggests a possible transition pathway into the final post-fusion conformation, highlighting the potential of MPER-specific broadly neutralizing antibodies to block membrane fusion.
Article
Multidisciplinary Sciences
Fritz Obermeyer, Martin Jankowiak, Nikolaos Barkas, Stephen F. Schaffner, Jesse D. Pyle, Leonid Yurkovetskiy, Matteo Bosso, Daniel J. Park, Mehrtash Babadi, Bronwyn L. MacInnis, Jeremy Luban, Pardis C. Sabeti, Jacob E. Lemieux
Summary: This study developed a model called PyR0 for rapid detection and characterization of new SARS-CoV-2 lineages, and identified mutations relevant to fitness. By applying PyR0 to all publicly available SARS-CoV-2 genomes, the researchers discovered mutations that increase fitness and predicted the growth of new lineages based on their mutational profile. The model also prioritizes mutations of biological and public health concern for further study.
Article
Biology
Noah J. Silverstein, Yetao Wang, Zachary Manickas-Hill, Claudia Carbone, Ann Dauphin, Brittany P. Boribong, Maggie Loiselle, Jameson Davis, Maureen M. Leonard, Leticia Kuri-Cervantes, Nuala J. Meyer, Michael R. Betts, Jonathan Z. Li, Bruce D. Walker, Xu G. Yu, Lael M. Yonker, Jeremy Luban
Summary: This study suggests that the abundance of specific lymphoid cell types is associated with the severity and recovery of COVID-19. Innate lymphoid cells (ILCs) decrease in number with age and in males, and their decreased abundance is seen in COVID-19 patients and children with MIS-C. However, the numbers of ILCs gradually recover in children with MIS-C. These results indicate that the abundance of lymphoid cell subsets plays a significant role in COVID-19 severity and recovery, potentially contributing to disease tolerance and tissue homeostasis.
Article
Microbiology
Anise N. Happi, Testimony J. Olumade, Olusola A. Ogunsanya, Ayotunde E. Sijuwola, Seto C. Ogunleye, Judith U. Oguzie, Cecilia Nwofoke, Chinedu A. Ugwu, Samuel J. Okoro, Patricia I. Otuh, Louis N. Ngele, Oluwafemi O. Ojo, Ademola Adelabu, Roseline F. Adeleye, Nicholas E. Oyejide, Clinton S. Njaka, Jonathan L. Heeney, Christian T. Happi
Summary: In Lassa fever endemic areas of Nigeria, the prevalence of Lassa virus is high in different species of rodents, indicating complex transmission dynamics and increased environmental contact in reservoirs. This has direct implications for understanding the transmission risk, mitigation, and prevention of Lassa fever in humans.
MICROBIOLOGY SPECTRUM
(2022)
Article
Infectious Diseases
Ana Atti, Ferdinando Insalata, Edward J. Carr, Ashley D. Otter, Javier Castillo-Olivares, Mary Wu, Ruth Harvey, Michael Howell, Andrew Chan, Jonathan Lyall, Nigel Temperton, Diego Cantoni, Kelly da Costa, Angalee Nadesalingam, Andrew Taylor-Kerr, Nipunadi Hettiarachchi, Caio Tranquillini, Jacqueline Hewson, Michelle J. Cole, Sarah Foulkes, Katie Munro, Edward J. M. Monk, Iain D. Milligan, Ezra Linley, Meera A. Chand, Colin S. Brown, Jasmin Islam, Amanda Semper, Andre Charlett, Jonathan L. Heeney, Rupert Beale, Maria Zambon, Susan Hopkins, Tim Brooks, Victoria Hall
Summary: This study investigated the serological differences between SARS-CoV-2 reinfection cases and controls, and identified antibody correlates of protection against reinfection. The results showed that before vaccination, protection against reinfection was directly correlated with anti-S levels, PV-N and LV-N titres, but not with anti-N levels.
JOURNAL OF INFECTION
(2022)
Article
Immunology
Kelly A. S. da Costa, Joanne Marie M. Del Rosario, Matteo Ferrari, Sneha Vishwanath, Benedikt Asbach, Rebecca Kinsley, Ralf Wagner, Jonathan L. Heeney, George W. Carnell, Nigel J. Temperton
Summary: By using NA pseudoviruses and developing the pELLA assay, we successfully measured neuraminidase inhibition levels in different influenza sera and found that pELLA is more sensitive than the commercially available NA-Fluor(TM). These studies may lead to the design of more potent, longer-lasting, and broader protective vaccines that can be used in a pre-pandemic approach in combination with HA vaccines.
Editorial Material
Infectious Diseases
Angalee Nadesalingam, Diego Cantoni, Ernest T. Aguinam, Andrew C. Y. Chan, Minna Paloniemi, Luis Ohlendorf, Charlotte George, George Carnell, Jon Lyall, Matteo Ferrari, Nigel Temperton, Ralf Wagner, Javier Castillo-Olivares, Helen Baxendale, Jonathan L. Heeney
Article
Microbiology
Balaji Olety, Yoshiko Usami, Yuanfei Wu, Paul Peters, Heinrich Gottlinger, Stephen P. Goff
Summary: The HIV-1 Nef protein downregulates the viral receptor CD4 and the antiviral proteins SERINC3 and SERINC5. In the absence of SERINC3 and SERINC5, Nef is no longer required for viral infectivity and replication in Jurkat Tag T cells, but remains crucial for HIV-1 replication in MOLT-3 cells. The Nef-mediated enhancement of HIV-1 replication in MOLT-3 cells is independent of the Nef-interacting kinases LCK and PAK2.
Article
Medicine, General & Internal
Felicity Liew, Shubha Talwar, Andy Cross, Brian J. Willett, Sam Scott, Nicola Logan, Matthew K. Siggins, Dawid Swieboda, Jasmin K. Sidhu, Claudia Efstathiou, Shona C. Moore, Chris Davis, Noura Mohamed, Jose Nunag, Clara King, A. A. Roger Thompson, Sarah L. Rowland-Jones, Annemarie B. Docherty, James D. Chalmers, Ling-Pei Ho, Alexander Horsley, Betty Raman, Krisnah Poinasamy, Michael Marks, Onn Min Kon, Luke Howard, Daniel G. Wootton, Susanna Dunachie, Jennifer K. Quint, Rachael A. Evans, Louise V. Wain, Sara Fontanella, Thushan I. de Silva, Antonia Ho, Ewen Harrison, J. Kenneth Baillie, Malcolm G. Semple, Christopher Brightling, Ryan S. Thwaites, Lance Turtle, Peter J. M. Openshaw
Summary: This study examined the nasal and plasma antibody responses in COVID-19 hospitalized patients one year after discharge and vaccination. The findings showed sustained elevated antibody responses in both nasal and plasma samples for at least 12 months, but the nasal antibody response was minimally influenced by vaccination. These findings highlight the importance of developing vaccines that enhance nasal immunity.
Review
Immunology
Kristine A. Moore, Tabitha Leighton, Julia T. Ostrowsky, Cory J. Anderson, Richard N. Danila, Angela K. Ulrich, Eve M. Lackritz, Angela J. Mehr, Ralph S. Baric, Norman W. Baylor, Bruce G. Gellin, Jennifer L. Gordon, Florian Krammer, Stanley Perlman, Helen Rees, Melanie Saville, Charlotte L. Weller, Michael T. Osterholm
Summary: Broadly protective coronavirus vaccines are crucial for future protection from SARS-CoV-2 variants and future outbreaks caused by novel coronaviruses. The Coronavirus Vaccines Research and Development (R&D) Roadmap aims to promote their development. It is funded by the Bill & Melinda Gates Foundation and The Rockefeller Foundation and involves collaboration with international experts. The roadmap outlines major research areas, milestones, and priorities for funding and research campaigns.
Article
Immunology
George W. Carnell, Martina Billmeier, Sneha Vishwanath, Maria Suau Sans, Hannah Wein, Charlotte L. George, Patrick Neckermann, Joanne Marie M. Del Rosario, Alexander T. Sampson, Sebastian Einhauser, Ernest T. Aguinam, Matteo Ferrari, Paul Tonks, Angalee Nadesalingam, Anja Schuetz, Chloe Qingzhou Huang, David A. Wells, Minna Paloniemi, Ingo Jordan, Diego Cantoni, David Peterhoff, Benedikt Asbach, Volker Sandig, Nigel Temperton, Rebecca Kinsley, Ralf Wagner, Jonathan L. Heeney
Summary: The rapid development of the first generation COVID-19 vaccines has saved millions of lives and potentially prevented long-term complications from SARS-CoV-2 infection. Successful vaccines have used the full-length SARS-CoV-2 spike protein as an immunogen. However, new variants have emerged, necessitating the development of next generation vaccines that target multiple neutralizing epitopes on the spike protein to provide broad protection against variant strains.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Hamish J. C. McAuley, Rachael A. Evans, Charlotte E. Bolton, Christopher E. Brightling, James D. Chalmers, Annemarie B. Docherty, Omer Elneima, Paul L. Greenhaff, Ayushman Gupta, Victoria C. Harris, Ewen M. Harrison, Ling-Pei Ho, Alex Horsley, Linzy Houchen-Wolloff, Caroline J. Jolley, Olivia C. Leavy, Nazir I. Lone, William D. C. Man, Michael Marks, Dhruv Parekh, Krisnah Poinasamy, Jennifer K. Quint, Betty Raman, Matthew Richardson, Ruth M. Saunders, Marco Sereno, Aarti Shikotra, Amisha Singapuri, Sally J. Singh, Michael Steiner, Ai Lyn Tan, Louise Wain, Carly Welch, Julie Whitney, Miles D. Witham, Janet Lord, Neil J. Greening, HOSP-COVID Study Collaborat Grp
Summary: This study recruited COVID-19 survivors in the UK and objectively measured frailty using FFP. The results showed that frailty and pre-frailty are common after hospitalization with COVID-19, and comprehensive assessment and interventions targeting frailty are needed beyond the initial illness.
Article
Biochemistry & Molecular Biology
Yetao Wang, Lawrence Lifshitz, Noah J. Silverstein, Esther Mintzer, Kevin Luk, Pamela StLouis, Michael A. Brehm, Scot A. Wolfe, Steven G. Deeks, Jeremy Luban
Summary: Innate lymphoid cells (ILCs) are a diverse population of cells that include NK cells and play important roles in tissue homeostasis and repair, inflammation, and protection from infection. This study used transcriptional and chromatin profiling to investigate the interplay between human blood ILCs and their responses to HIV-1 infection. The findings reveal the existence of four main ILC subsets in human blood and provide insights into how HIV-1 infection disrupts NK cells and their homeostatic function.
Article
Multidisciplinary Sciences
Guangai Xue, Hyun Jae Yu, Cindy Buffone, Szu-Wei Huang, KyeongEun Lee, Shih Lin Goh, Anna T. T. Gres, Mehmet Hakan Guney, Stefan G. G. Sarafianos, Jeremy Luban, Felipe Diaz-Griffero, Vineet N. N. KewalRamani
Summary: The entry of HIV-1 into the nucleus is regulated by the interaction between the viral capsid protein CA and nuclear pore complex proteins Nup35 and POM121. This interaction is also influenced by soluble host factors such as Cyclophilin A. These findings highlight the role of CA as a macromolecular nuclear transport receptor and provide insights into the mechanism of HIV-1 nuclear invasion.
NATURE COMMUNICATIONS
(2023)
Article
Engineering, Biomedical
Sneha Vishwanath, George William Carnell, Matteo Ferrari, Benedikt Asbach, Martina Billmeier, Charlotte George, Maria Suau Sans, Angalee Nadesalingam, Chloe Qingzhou Huang, Minna Paloniemi, Hazel Stewart, Andrew Chan, David Arthur Wells, Patrick Neckermann, David Peterhoff, Sebastian Einhauser, Diego Cantoni, Martin Mayora Neto, Ingo Jordan, Volker Sandig, Paul Tonks, Nigel Temperton, Simon Frost, Katharina Sohr, Maria Teresa Lluesma Ballesteros, Farzad Arbabi, Johannes Geiger, Christian Dohmen, Christian Plank, Rebecca Kinsley, Ralf Wagner, Jonathan Luke Heeney
Summary: A computationally designed antigen based on the spike protein of sarbecoviruses elicits broad humoral responses against severe acute respiratory syndrome viruses in mice, rabbits, and guinea pigs.
NATURE BIOMEDICAL ENGINEERING
(2023)
Article
Immunology
Alberto Grandi, Michele Tomasi, Irfan Ullah, Cinzia Bertelli, Teresa Vanzo, Silvia Accordini, Assunta Gagliardi, Ilaria Zanella, Mattia Benedet, Riccardo Corbellari, Gabriele Di Lascio, Silvia Tamburini, Elena Caproni, Lorenzo Croia, Micol Rava, Valeria Fumagalli, Pietro Di Lucia, Davide Marotta, Eleonora Sala, Matteo Iannacone, Priti Kumar, Walther Mothes, Pradeep D. Uchil, Peter Cherepanov, Martino Bolognesi, Massimo Pizzato, Guido Grandi
Summary: The study demonstrates that engineered OMVs vaccines can induce effective immune responses, producing neutralizing antibodies and protecting animals from SARS-CoV-2 infection. Furthermore, the vaccine can also elicit immune responses against the Omicron BA.1 and BA.5 variants. OMV-based SARS-CoV-2 vaccines, with the convenience of engineering, production, and distribution, can be a crucial addition to the currently available vaccines.