Review
Immunology
Rina Fajri Nuwarda, Abdulsalam Abdullah Alharbi, Veysel Kayser
Summary: Influenza is a major public health concern, and vaccines are an effective method for prevention and control. New vaccine platforms and advancements in vaccine manufacturing processes are being explored to improve effectiveness and stability.
Review
Immunology
Christopher L. D. McMillan, Paul R. Young, Daniel Watterson, Keith J. Chappell
Summary: Current influenza virus vaccines mainly induce antibodies against the highly variable head domain of the hemagglutinin protein, but these antibodies are often strain-specific, resulting in limited cross-protection. Therefore, the annual update of vaccine formulations to counteract the challenge of influenza virus evolution is crucial.
Review
Immunology
Claudia Maria Trombetta, Otfried Kistner, Emanuele Montomoli, Simonetta Viviani, Serena Marchi
Summary: Influenza is a vaccine preventable disease and vaccination is the most effective method of controlling the morbidity and mortality of seasonal influenza, especially among risk groups. The effectiveness of current influenza vaccines is suboptimal, but they are still effective against morbidity and mortality in all age and risk groups, particularly in young children and older adults.
Article
Virology
Atsushi Kawai, Yasuyuki Yamamoto, Takuto Nogimori, Kohei Takeshita, Takuya Yamamoto, Yasuo Yoshioka
Summary: The study demonstrates that intranasal immunization with NA provides broad cross-protection against both homologous and heterologous influenza viruses by inducing NA-specific IgA that recognizes a wider range of epitopes, indicating the potential of NA as an antigen for nasal vaccines to provide broad cross-protection.
JOURNAL OF VIROLOGY
(2021)
Review
Immunology
Maya Sangesland, Daniel Lingwood
Summary: Influenza virus remains a serious public health burden due to ongoing viral evolution. Current seasonal vaccines elicit strain-specific responses, but universal vaccine development aims to redirect immune responses to conserved sites for broad coverage, which is challenging due to immunological barriers.
Article
Virology
Hae-Ji Kang, Ki-Back Chu, Keon-Woong Yoon, Gi-Deok Eom, Jie Mao, Min-Ju Kim, Su-Hwa Lee, Eun-Kyung Moon, Fu-Shi Quan
Summary: Research suggests that avian influenza VLP vaccines expressing multiple neuraminidases can provide both homologous and heterosubtypic protection against different subtypes, offering a promising approach for developing a universal influenza A vaccine against avian and human influenza virus infections.
Review
Immunology
Yo Han Jang, Baik L. Seong
Summary: Influenza virus infection poses a major public health challenge, with current vaccines potentially compromised by viral antigenic changes. Efforts are underway to develop a universal influenza vaccine that provides long-lasting and broad protection. Immune responses induced by live attenuated influenza vaccines (LAIVs), including neutralizing antibodies, T cell responses, and mucosal immunity, show promising potential for serving as attractive platforms for a universal influenza vaccine.
Review
Virology
Jiali Li, Yifan Zhang, Xinglong Zhang, Longding Liu
Summary: China has a high number of influenza cases and deaths, and the effectiveness of the flu vaccine is reduced due to viral antigenic drift. Therefore, the development of a universal influenza vaccine is necessary.
Review
Immunology
SangJoon Lee, Jin-Hyeob Ryu
Summary: The innate immune system serves as the first line of defense against influenza viruses, and mRNA vaccines are being explored as a promising alternative to traditional approaches due to their safety, cost-effectiveness, rapid development capabilities, and high efficacy. This review provides insights into the innate immune response to mRNA vaccination, as well as discusses the future directions and challenges in advancing this promising therapeutic approach.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Vasilis C. Pliasas, Zach Menne, Virginia Aida, Ji-Hang Yin, Maria C. Naskou, Peter J. Neasham, J. Fletcher North, Dylan Wilson, Katharine A. Horzmann, Joshy Jacob, Ioanna Skountzou, Constantinos S. Kyriakis
Summary: This study evaluated the immunogenicity and efficacy of a novel vaccine against influenza virus infection in a pig model. The results showed that the vaccine induced high levels of anti-NA antibodies and provided protection comparable to a commercial vaccine.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Eduard Puente-Massaguer, Annika Beyer, Madhumathi Loganathan, Iden Sapse, Juan Manuel Carreno, Goran Bajic, Weina Sun, Peter Palese, Florian Krammer
Summary: Seasonal influenza viruses cause 1 billion infections per year, with millions of severe cases and hundreds of thousands of deaths. Current influenza vaccines have varying effectiveness and target the HA and NA surface glycoproteins. This study developed a bioprocess to manufacture inactivated split cHA and mHA vaccines and a method to quantify HA with a prefusion stalk. The process demonstrated high yield and low levels of impurities, providing a basis for pre-clinical and future clinical trials.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Virology
Amanda L. Skarlupka, Anne-Gaelle Bebin-Blackwell, Spencer F. Sumner, Ted M. Ross
Summary: The N1-I COBRA NA vaccine antigen showed cross-reactivity with various influenza viruses, providing protection and lower lung viral titers in mice challenged with different viral strains. This research suggests that the NA antigen has the potential to enhance the breadth of protection in a universal influenza vaccine formulation.
JOURNAL OF VIROLOGY
(2021)
Article
Multidisciplinary Sciences
Daniel Ellis, Julia Lederhofer, Oliver J. Acton, Yaroslav Tsybovsky, Sally Kephart, Christina Yap, Rebecca A. Gillespie, Adrian Creanga, Audrey Olshefsky, Tyler Stephens, Deleah Pettie, Michael Murphy, Claire Sydeman, Maggie Ahlrichs, Sidney Chan, Andrew J. Borst, Young-Jun Park, Kelly K. Lee, Barney S. Graham, David Veesler, Neil P. King, Masaru Kanekiyo
Summary: This study reveals the conformational stability of influenza virus neuraminidase (NA) and demonstrates how recombinant NA antigens can be strengthened through structure-based design.
NATURE COMMUNICATIONS
(2022)
Article
Microbiology
Xiren Deng, Qimin Wang, Mei Liu, Qinwen Zheng, Fan Wu, Jinghe Huang
Summary: In this study, it was found that tetrameric NA with natural conformation is necessary to induce protective anti-NA immunity. The NA tetramer provides homologous protection and subtype-specific cross-protection. Additionally, aluminum adjuvant is preferred in recombinant NA protein vaccination.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Virology
Nada Abbadi, Jarrod J. Mousa
Summary: Neuraminidase (NA) is an important surface protein on influenza virions, playing a crucial role in the viral life cycle and being a target of the immune system. Vaccines currently focus on the hemagglutinin (HA) protein, but NA-specific antibodies have shown promise in reducing infection severity. This review summarizes the characteristics of NA, NA-specific antibodies, NA inhibition mechanism, and recent developments in NA-based influenza vaccines.
Article
Multidisciplinary Sciences
Jennifer Cable, Siddharth Balachandran, Lisa P. Daley-Bauer, Arjun Rustagi, Ferrin Antony, Justin J. Frere, Jamie Strampe, Katherine Kedzierska, Judy L. Cannon, Maureen A. McGargill, Daniela Weiskopf, Robert C. Mettelman, Julia Niessl, Paul G. Thomas, Bryan Briney, Sophie A. Valkenburg, Jesse D. Bloom, Pamela J. Bjorkman, Sho Iketani, C. Garrett Rappazzo, Chelsea M. Crooks, Kali F. Crofts, Stefan Pohlmann, Florian Krammer, Andrea J. Sant, Gary J. Nabel, Stacey Schultz-Cherry
Summary: Millions of people are infected by viruses each year, which pose ongoing threats to global public health. To develop more effective tools against viruses, a comprehensive understanding of the virus itself and our immune system's response to infection is necessary. The Keystone symposium Viral Immunity: Basic Mechanisms and Therapeutic Applications, held from June 29 to July 2, 2022, brought together researchers to discuss these topics, and this report provides concise summaries from several presenters at the symposium.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Laura Klenow, Rageia Elfageih, Jin Gao, Hongquan Wan, Stephen G. Withers, Jan-Willem de Gier, Robert Daniels
Summary: Influenza A viruses and pneumococci both express neuraminidases that catalyze release of sialic acid residues. The enzymatic properties of neuraminidases from both pathogens were compared, and it was found that they have evolved similar yet distinct strategies to optimize their catalytic activity.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Robert Haupt, Lauren Baracco, Erin M. Harberts, Madhumathi Loganathan, Lucas J. Kerstetter, Florian Krammer, Lynda Coughlan, Robert K. Ernst, Matthew B. Frieman
Summary: The BECC438 and BECC470 adjuvants formulated with an influenza virus hemagglutinin (HA) protein vaccine provide enhanced protection against influenza virus in adult mouse respiratory models. Immunization with HA + BECC adjuvants also broadens the epitopes targeted on HA and increases antibody titers against the conserved HA stalk domain. Furthermore, BECC470 combined with an influenza virus HA protein antigen achieves complete protection in a aged mouse model.
SCIENTIFIC REPORTS
(2023)
Article
Engineering, Biomedical
Steven J. Frey, Juan Manuel Carreno, Dominika Bielak, Ammar Arsiwala, Clara G. Altomare, Chad Varner, Tania Rosen-Cheriyan, Goran Bajic, Florian Krammer, Ravi S. Kane
Summary: Despite licensed vaccines being available, influenza still leads to significant illness and death globally. Current vaccines mainly target the head domain of the viral protein hemagglutinin (HA), but influenza viruses can easily evade this response by acquiring mutations in the head domain. This study demonstrates that nanoparticles presenting HA in an inverted orientation generate higher levels of antibodies and a broader immune response against the conserved stalk domain, providing better protection against the virus. By controlling antigen orientation, it may be possible to design nanovaccines that offer broad protection against influenza and other potential pandemic pathogens.
ADVANCED HEALTHCARE MATERIALS
(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
Gagandeep Singh, Anass Abbad, Johnstone Tcheou, Demodara Rao Mendu, Adolfo Firpo-Betancourt, Charles Gleason, Komal Srivastava, Carlos Cordon-Cardo, Viviana Simon, Florian Krammer, Juan Manuel Carreno
Summary: This study investigates the impact of exposures to SARS-CoV-2 infection and vaccine antigens on the antibody response. The results show that binding and avidity of antibodies increase with the number of exposures to infection and/or vaccination. However, cross-reactivity of the antibody response after BA.1 breakthroughs is affected by the number of prior exposures.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Virology
Fatima Amanat, Jordan Clark, Juan Manuel Carreno, Shirin Strohmeier, Temima Yellin, Philip S. Meade, Disha Bhavsar, Hiromi Muramatsu, Weina Sun, Lynda Coughlan, Norbert Pardi, Florian Krammer
Summary: Seasonal coronaviruses have been circulating widely in the human population and it has been hypothesized that immunity to these viruses may provide partial protection against SARS-CoV-2 infection. COVID-19 vaccination has also been shown to boost immunity against seasonal betacoronaviruses.
JOURNAL OF VIROLOGY
(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
Biotechnology & Applied Microbiology
Eduard Puente-Massaguer, Annika Beyer, Madhumathi Loganathan, Iden Sapse, Juan Manuel Carreno, Goran Bajic, Weina Sun, Peter Palese, Florian Krammer
Summary: Seasonal influenza viruses cause 1 billion infections per year, with millions of severe cases and hundreds of thousands of deaths. Current influenza vaccines have varying effectiveness and target the HA and NA surface glycoproteins. This study developed a bioprocess to manufacture inactivated split cHA and mHA vaccines and a method to quantify HA with a prefusion stalk. The process demonstrated high yield and low levels of impurities, providing a basis for pre-clinical and future clinical trials.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(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.
Article
Infectious Diseases
Hallie Cohn, Nathaniel Bloom, Gianna Y. Cai, Jordan J. Clark, Alison Tarke, Maria C. Bermudez-Gonzalez, Deena R. Altman, Luz Amarilis Lugo, Francisco Pereira Lobo, Susanna Marquez, Jin-Qiu Chen, Wenlin Ren, Lili Qin, Jennifer L. Yates, Danielle T. Hunt, William T. Lee, Shane Crotty, Florian Krammer, Alba Grifoni, Alessandro Sette, Viviana Simon, Camila H. Coelho
Summary: This study compares human immune responses to JYNNEOS vaccination and monkeypox virus infection. The results show that infection with monkeypox virus elicits robust B-cell and T-cell responses, while JYNNEOS vaccination mainly induces T-cell responses.
LANCET INFECTIOUS DISEASES
(2023)
Article
Multidisciplinary Sciences
Eduard Puente-Massaguer, Kirill Vasilev, Annika Beyer, Madhumathi Loganathan, Benjamin Francis, Michael J. Scherm, Guha Asthagiri Arunkumar, Irene Gonzalez-Dominguez, Xueyong Zhu, Ian A. Wilson, Lynda Coughlan, Weina Sun, Peter Palese, Florian Krammer
Summary: In this study, it was shown that immunization with group 2 cHA split vaccines in combination with the CpG 1018 adjuvant elicited broadly cross-reactive antibodies against various influenza A viruses, providing immune protection.