Review
Immunology
Rory D. de Vries, Katja Hoschler, Guus F. Rimmelzwaan
Summary: In this review, the results of an assay to detect influenza virus-specific antibodies that mediate ADCC were summarized. The study found that HA-specific ADCC mediating antibodies can be detected in serum samples from individuals vaccinated or infected with influenza viruses. The presence of cross-reactive antibodies and their immunological functionalities were also investigated. The findings suggest that virus-specific antibodies induced by infection or vaccination have additional immunological functionalities that contribute to protective immunity.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Engineering, Biomedical
Yufeng Song, Wandi Zhu, Ye Wang, Lei Deng, Yao Ma, Chunhong Dong, Gilbert X. Gonzalez, Joo Kim, Lai Wei, Sang -Moo Kang, Bao-Zhong Wang
Summary: Influenza B vaccine efficacy is limited by antigenicity changes, but this study developed double-layered protein nanoparticles incorporating structure-stabilized antigens, effectively inducing broad immune responses and providing cross-immune protection against multiple influenza B virus strains.
Article
Microbiology
Huihui Kong, David F. Burke, Tiago Jose da Silva Lopes, Kosuke Takada, Masaki Imai, Gongxun Zhong, Masato Hatta, Shufang Fan, Shiho Chiba, Derek Smith, Gabriele Neumann, Yoshihiro Kawaoka
Summary: The study demonstrates the substantial plasticity of the influenza virus H5 HA protein, which may lead to the emergence of novel antigenic variants.
Article
Immunology
Francesca Ferrara, Joanne Marie M. Del Rosario, Kelly A. S. da Costa, Rebecca Kinsley, Simon Scott, Sasan Fereidouni, Craig Thompson, Paul Kellam, Sarah Gilbert, George Carnell, Nigel Temperton
Summary: Traditional methods to assess influenza vaccine immunogenicity have limitations, leading researchers to develop innovative approaches using pseudotypes to study antibody responses. These pseudotypes show promise as effective tools in influenza research.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Mallory L. Myers, John R. Gallagher, Alexander J. Kim, Walker H. Payne, Samantha Maldonado-Puga, Haralabos Assimakopoulos, Kevin W. Bock, Udana Torian, Ian N. Moore, Audray K. Harris
Summary: Influenza viruses cause worldwide epidemics and yearly reformulation of commercial influenza vaccines (CIV) due to the antigenic variation of Hemagglutinin (HA). This study investigates the structural organization of HA in four current CIVs using electron microscopy, revealing different arrangements including individual HAs, starfish structures, and spiked-nanodisc structures. CIVs with spiked nanodiscs induce the highest levels of cross-reactive antibodies. Therefore, HA structural organization can be an important parameter for CIVs and their efficacy.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Katherine Kaugars, Joseph Dardick, Anna Paula de Oliveira, Kayla A. Weiss, Regy Lukose, John Kim, Lawrence Leung, Saranathan Rajagopalan, Sydney Wolin, Leor Akabas, David M. Knipe, Goran Bajic, William R. Jacobs Jr
Summary: Despite annual vaccination efforts, influenza continues to cause significant morbidity and mortality worldwide. To improve vaccine efficacy, researchers are exploring the use of antibodies that can activate immune cell effector functions, such as ADCC. Evidence suggests that ADCC is crucial for protection against influenza and other infectious diseases, leading to the development of innovative vaccine strategies such as using Delta gD-2 as a vector for a broadly protective influenza vaccine.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Pharmacology & Pharmacy
Chia-Ying Wu, Shao-En Kao, Yung-Chieh Tseng, Yu-Po Lin, Jen-Tzu Hou, Li-Yang Wu, Sharon Chiu, Che Alex Ma, Pei-Wen Hsiao, Jane Hsiao, Juine-Ruey Chen
Summary: Influenza epidemics and pandemics caused by newly emerging virus strains call for the development of a universal vaccine. A monoglycosylated vaccine has been shown to provide broader protection in mice than conventional vaccines, but the challenge lies in developing a robust manufacturing process for mass production and verifying its immunogenicity in inducing cross-protective immunity.
ANTIVIRAL RESEARCH
(2023)
Article
Microbiology
Zhao Wang, Jieshi Yu, Zizhang Sheng, Ben M. Hause, Feng Li, Radhey S. Kaushik, Dan Wang
Summary: The N-terminal B-loop and CD helix of the HA2 protein in swine influenza A virus play a significant role in virus replication, with mutations in these regions attenuating virus replication. These mutations could potentially be explored as attenuated vaccine candidates to prevent the spread of influenza within swine populations.
VETERINARY MICROBIOLOGY
(2021)
Article
Nanoscience & Nanotechnology
Chunhong Dong, Ye Wang, Wandi Zhu, Yao Ma, Joo Kim, Lai Wei, Gilbert X. Gonzalez, Bao-Zhong Wang
Summary: In this study, PEI-HA/CpG nanoparticles were developed as a potential cross-protective influenza vaccine. The nanoparticles significantly enhanced HA immunogenicity, inducing robust and balanced antibody responses and cellular immune responses. These immune responses remained strong even after six months of observation post-immunization.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Medicine, Research & Experimental
Iuliia M. Gilchuk, Sandhya Bangaru, Nurgun Kose, Robin G. Bombardi, Andrew Trivette, Sheng Li, Hannah L. Turner, Robert H. Carnahan, Andrew B. Ward, James E. Crowe Jr
Summary: This study examined the B cell response to H7 HA in individuals who had recovered from natural H7N9 virus infection. Circulating H7-reactive B cells were found to recognize a diverse antigenic landscape on the HA molecule and exhibit broad recognition of unrelated H7 strains. Functional testing of the antibodies revealed diverse patterns of inhibition, including neutralizing and HA trimer-disrupting activities.
Article
Chemistry, Analytical
Rozaleen Dash, Anurag S. Rathore
Summary: Both freeze-thaw and lyophilization induce protein aggregation in therapeutic monoclonal antibody products, leading to decreased biological potency over time. Acidic pools and basic variants increase, while binding affinity and potency decrease with repeated cycles of freeze-thaw and lyophilization. The impact on binding affinity is greater with lyophilization compared to freeze-thaw, affecting both innovator and biosimilar products similarly.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2021)
Article
Biochemical Research Methods
Aditya Narvekar, Apurva Pardeshi, Ratnesh Jain, Prajakta Dandekar
Summary: This article discusses strategies to enhance antibody dependent cell mediated cytotoxicity (ADCC) and improve the therapeutic efficacy of monoclonal antibodies (mAbs). By modifying the elements of the ADCC mechanism, such as the effector cell or the antibody itself, the therapeutic response can be enhanced. Several ADCC enhancement technologies have been developed, but their effectiveness varies depending on the antibody therapy.
Article
Immunology
Aafke Aartse, Daniella Mortier, Petra Mooij, Sam Hofman, Marlies M. van Haaren, Martin Corcoran, Gunilla B. Karlsson Hedestam, Dirk Eggink, Mathieu Claireaux, Willy M. J. M. Bogers, Marit J. van Gils, Gerrit Koopman
Summary: Studies have shown that the initial encounter with influenza virus influences the immune response to subsequent infections or vaccinations. However, there is a lack of detailed analysis on the primary antibody response in humans. This study evaluated the frequency and dynamics of strain-specific hemagglutinin (HA) head- and stem-directed antibody responses following primary influenza virus infection in cynomolgus macaques. The results demonstrated an early induction of HA-stem antibody responses, which decreased over time. In contrast, HA-head antibody responses were initially low but increased later. The study also revealed diverse VH-gene usage and allelic variation within the VH-usage in HA-specific B cell repertoires. Furthermore, HA-head B cells had shorter CDRH3s and higher VH-gene somatic hyper mutation levels compared to HA-stem B cells. Overall, these findings suggest that HA-stem antibodies respond first to the infection, while HA-head antibodies show a delayed response but have a greater potential for affinity maturation in germinal centers.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Engineering, Chemical
Alexandre B. Murad, Marcos Q. Sousa, Ricardo Correia, Ines A. Isidro, Manuel J. T. Carrondo, Antonio Roldao
Summary: By analyzing the metabolic features of insect cells producing different hemagglutinin vaccines, this study found that different hemagglutinin strains and vaccine complexity affect production yield. Higher metabolic rates do not necessarily mean higher vaccine expression, and specific metabolites play a crucial role in central carbon metabolism during vaccine expression.
Article
Multidisciplinary Sciences
Makoto Saito, Yasushi Itoh, Fumihiko Yasui, Tsubasa Munakata, Daisuke Yamane, Makoto Ozawa, Risa Ito, Takayuki Katoh, Hirohito Ishigaki, Misako Nakayama, Shintaro Shichinohe, Kenzaburo Yamaji, Naoki Yamamoto, Ai Ikejiri, Tomoko Honda, Takahiro Sanada, Yoshihiro Sakoda, Hiroshi Kida, Thi Quynh Mai Le, Yoshihiro Kawaoka, Kazumasa Ogasawara, Kyoko Tsukiyama-Kohara, Hiroaki Suga, Michinori Kohara
Summary: Researchers have developed a class of macrocyclic peptides named iHA, which can bind the influenza viral envelope protein hemagglutinin and inhibit virus infection by blocking adsorption and fusion. Particularly, iHA-100 shows powerful efficacy in inhibiting the growth of highly pathogenic influenza viruses and preventing severe pneumonia at later stages of infection in mouse and non-human primate cynomolgus macaque models, indicating its potential as a next-generation, mid-sized biomolecule.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Savannah A. Moritzky, Katherine A. Richards, Maryah A. Glover, Florian Krammer, Francisco A. Chaves, David J. Topham, Angela Branche, Jennifer L. Nayak, Andrea J. Sant
Summary: The influence of preexisting immunity specific for influenza A H1 and H3 proteins on human responses to influenza vaccines was investigated. It was found that this accumulated immunity is associated with diminished future responses to the vaccines, regardless of the vaccine formulation administered and the subjects' influenza vaccine history. The study highlights the importance of yearly vaccination to establish diverse repertoires of B cells, antibodies, and T cells.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Clinical Neurology
Ilana Katz Sand, Sacha Gnjatic, Florian Krammer, Kevin Tuballes, Juan Manuel Carreno, Sammita Satyanarayan, Susan Filomena, Erin Staker, Johnstone Tcheou, Aaron Miller, Michelle Fabian, Neha Safi, Jamie Nichols, Jasmin Patel, Stephen Krieger, Stephanie Tankou, Sam Horng, Sylvia Klineova, Erin Beck, Miriam Merad, Fred Lublin
Summary: This study evaluates humoral and cellular immune responses to a third COVID-19 vaccine dose in patients on anti-CD20 therapy and S1PR modulators, including Omicron-specific assays. The results show that participants on anti-CD20 therapy have lower levels of neutralizing antibodies, particularly against the BA.1 variant, but their cellular immune responses are not significantly different from healthy controls. Participants on S1PR modulator therapy have significantly reduced levels of neutralizing antibodies and cellular immune responses. These findings have clinical implications and require further study.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2023)
Article
Immunology
Paulina Kaplonek, Deniz Cizmeci, Gaurav Kwatra, Alane Izu, Jessica Shih-Lu Lee, Harry L. Bertera, Stephanie Fischinger, Colin Mann, Fatima Amanat, Wenjun Wang, Anthonet L. Koen, Lee Fairlie, Clare L. Cutland, Khatija Ahmed, Keertan Dheda, Shaun L. Barnabas, Qasim Ebrahim Bhorat, Carmen Briner, Florian Krammer, Erica Ollman Saphire, Sarah C. Gilbert, Teresa Lambe, Andrew J. Pollard, Marta Nunes, Manfred Wuhrer, Douglas A. Lauffenburger, Shabir A. Madhi, Galit Alter
Summary: Despite the success of COVID-19 vaccines, breakthrough infections can occur due to SARS-CoV-2 variants. The immune mediators of protection in humans are still unknown. A study on ChAdOx1 nCoV-19 (AZD1222) vaccine recipients in South Africa found different Fc-receptor-binding antibodies among different groups. Individuals who resisted COVID-19 exclusively had Fc gamma R3B-binding antibodies, while those who experienced breakthrough had enhanced IgA and IgG3 with enriched Fc gamma R2B binding. Antibodies unable to bind to Fc gamma R3B led to immune complex clearance and inflammation. The differential antibody binding to Fc gamma R3B was associated with Fc-glycosylation differences in SARS-CoV-2-specific antibodies.
Article
Immunology
Wuji Zhang, Lukasz Kedzierski, Brendon Y. Chua, Mark Mayo, Claire Lonzi, Vanessa Rigas, Bianca F. Middleton, Hayley A. McQuilten, Louise C. Rowntree, Lilith F. Allen, Ruth A. Purcell, Hyon-Xhi Tan, Jan Petersen, Priyanka Chaurasia, Francesca Mordant, Mikhail V. Pogorelyy, Anastasia A. Minervina, Jeremy Chase Crawford, Griffith B. Perkins, Eva Zhang, Stephanie Gras, E. Bridie Clemens, Jennifer A. Juno, Jennifer Audsley, David S. Khoury, Natasha E. Holmes, Irani Thevarajan, Kanta Subbarao, Florian Krammer, Allen C. Cheng, Miles P. Davenport, Branka Grubor-Bauk, P. Toby Coates, Britt Christensen, Paul G. Thomas, Adam K. Wheatley, Stephen J. Kent, Jamie Rossjohn, Amy W. Chung, John Boffa, Adrian Miller, Sarah Lynar, Jane Nelson, Thi H. O. Nguyen, Jane Davies, Katherine Kedzierska
Summary: Kedzierska et al. found that there is an association between low production of receptor-binding domain (RBD) antibodies after mRNA vaccination and altered glycosylation of IgG before vaccination in people with comorbidities. This condition disproportionately affects Australia's First Nations peoples due to their high burden of comorbidities. The study also showed that Indigenous people, including Australian First Nations peoples, have effective immune responses to COVID-19 vaccination.
Article
Obstetrics & Gynecology
Christina L. Marshall, Elianna Kaplowitz, Erona Ibroci, Kyle Chung, Frederieke A. J. Gigase, Molly Lieber, Mara Graziani, Sophie Ohrn, Jezelle Lynch, Juliana Castro, Rushna Tubassum, Farida Mutawakil, Rebecca Jessel, Nina Molenaar, Anna-Sophie Rommel, Rhoda S. Sperling, Elizabeth A. Howell, Hannah Feldman, Florian Krammer, Daniel Stadlbauer, Lotje D. de Witte, Veerle Bergink, Joanne Stone, Teresa Janevic, Siobhan M. Dolan, Whitney Lieb
Summary: We investigated the differences in SARS-CoV-2 antibody responses among pregnant individuals with natural immunity, vaccine-induced immunity, or combined immunity. Our study included 260 participants with seropositive results and information on mRNA vaccination and infection. We found that individuals with combined immunity had significantly higher anti-S titers compared to those with natural or vaccine-induced immunity.
OBSTETRICS AND GYNECOLOGY
(2023)
Article
Cell Biology
Juan Manuel Carreno, Ariel Raskin, Gagandeep Singh, Johnstone Tcheou, Hisaaki Kawabata, Charles Gleason, Komal Srivastava, Vladimir Vigdorovich, Nicholas Dambrauskas, Sneh Lata Gupta, Irene Gonzalez Dominguez, Jose Luis Martinez, Stefan Slamanig, D. Noah Sather, Rama Raghunandan, Ponthip Wirachwong, Sant Muangnoicharoen, Punnee Pitisuttithum, Jens Wrammert, Mehul S. Suthar, Weina Sun, Peter Palese, Adolfo Garcia-Sastre, Viviana Simon, Florian Krammer
Summary: NDV-HXP-S, a recombinant Newcastle disease virus-based vaccine expressing an optimized spike protein, shows comparable neutralizing activity but lower spike protein binding activity than the mRNA BNT162b2 (Pfizer) vaccine in postvaccination serum samples from a phase 1 clinical study in Thailand. Unlike mRNA vaccination, NDV-HXP-S vaccination elicits a focused antibody response to the receptor binding domain (RBD) and has a high proportion of neutralizing antibodies. Overall, NDV-HXP-S vaccination induces a high proportion of neutralizing antibodies similar to that of mRNA vaccination.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
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
Multidisciplinary Sciences
Ana Gonzalez-Reiche, Hala Alshammary, Sarah Schaefer, Gopi F. Patel, Jose C. Polanco, Juan Manuel Carreno, Angela Amoako, Aria Rooker, Christian Cognigni, Daniel Floda, Adriana van de Guchte, Zain Khalil, Keith Farrugia, Nima Assad, Jian Zhang, Bremy A. Alburquerque, Levy Sominsky, Charles Gleason, Komal Srivastava, Robert Sebra, Juan David Ramirez, Radhika Banu, Paras Shrestha, Florian Krammer, Alberto Paniz-Mondolfi, Emilia Mia Sordillo, Viviana Simon, Harm van Bakel
Summary: This study describes sequential persistent SARS-CoV-2 infections in three individuals, leading to the emergence and transmission of a new Omicron BA.1.23 lineage. These infections demonstrate that the Omicron BA.1 lineage can further diverge from its already mutated genome, and patients with persistent infections can transmit these viral variants. Therefore, urgent strategies are needed to prevent prolonged SARS-CoV-2 replication and limit the spread of newly emerging, neutralization-resistant variants in vulnerable patients.
NATURE COMMUNICATIONS
(2023)
Letter
Infectious Diseases
Juan Manuel Carreno, Gagandeep Singh, Viviana Simon, Florian Krammer
Article
Infectious Diseases
Lisa Seekircher, Zoltan Banki, Janine Kimpel, Annika Roessler, Helena Schaefer, Barbara Falkensammer, David Bante, Lukas Forer, Sebastian Schonherr, Teresa Harthaller, Magdalena Sacher, Cornelia Ower, Lena Tschiderer, Hanno Ulmer, Florian Krammer, Dorothee von Laer, Wegene Borena, Peter Willeit
Summary: This study investigated the associations between antibody and T-cell responses after COVID-19 vaccination and the risk of SARS-CoV-2 breakthrough infection, as well as whether measurement of these responses enhances risk prediction.
Review
Immunology
Florian Krammer
SEMINARS IN IMMUNOPATHOLOGY
(2023)
Meeting Abstract
Oncology
Sooyun Tavolacci, Philip C. Mack, Jorge E. Gomez, Nicholas Rohs, Ananda M. Rodilla, Diego De Miguel Perez, Juan Manuel Carreno, Chin-Yuan Hsu, Jazz Cagan, Christian Rolfo, Amy Moore, Rachel I. Brody, Jennifer C. King, David E. Gerber, Claudia I. Henschke, David F. Yankelevitz, John D. Minna, Paul Bunn, Adolfo Garcia-Sastre, Florian Krammer, Yu Shyr, Fred R. Hirsch
JOURNAL OF THORACIC ONCOLOGY
(2023)
Article
Medicine, Research & Experimental
Siriruk Changrob, Peter J. Halfmann, Hejun Liu, Jonathan L. Torres, Joshua J. C. McGrath, Gabriel Ozorowski, Lei Li, G. Dewey Wilbanks, Makoto Kuroda, Tadashi Maemura, Min Huang, Nai-Ying Zheng, Hannah L. Turner, Steven A. Erickson, Yanbin Fu, Atsuhiro Yasuhara, Gagandeep Singh, Brian Monahan, Jacob Mauldin, Komal Srivastava, Viviana Simon, Florian Krammer, D. Noah Sather, Andrew B. Ward, Ian A. Wilson, Yoshihiro Kawaoka, Patrick C. Wilson
Summary: In this study, a broadly neutralizing antibody (bnAb) called S728-1157 was identified, which can neutralize various SARS-CoV-2 variants, including Omicron. The antibody showed therapeutic potential in animal models and may be useful for vaccine design against future SARS-CoV-2 variants.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Immunology
Florian Krammer, Stacey Schultz-Cherry
Summary: Recent evidence of avian H5N1 virus transmission among mammals raises concerns about its potential for a pandemic. We need to increase awareness, preparedness, and adopt safe farming practices to prevent the emergence of concerning pathogens in the future.
NATURE REVIEWS IMMUNOLOGY
(2023)
Meeting Abstract
Oncology
Adolfo Aleman, Morgan van Kesteren, Ariel Kogan-Zajdman, Bhaskar Upadhyaya, Lucia Chen, Annika Oostenink, Kseniya Serebryakova, Komal Srivastava, Katerina Kappes, Hayley Jackson, Charles Gleason, Juan Manuel Carreno Quiroz, Carlos Cordon-Cardo, Ania Wajnberg, Florian Krammer, Sundar Jagannath, Viviana Simon, Samir Parekh
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)