Bivalent H1 and H3 COBRA Recombinant Hemagglutinin Vaccines Elicit Seroprotective Antibodies against H1N1 and H3N2 Influenza Viruses from 2009 to 2019
James D. Allen,Ted M. Ross +1 more
TLDR
Overall, the newly generated COBRA HA antigens had the ability to induce broadly reactive antibodies in influenza-naive and preimmune animals in both monovalent and bivalent formulations, and these antIGens outperformed H1 and H3 WT rHA vaccine antigen by eliciting seroprotective antibodies against panels of antigenically drifted historical H1N1 andH3N2 vaccine strains from 2009 to 2019.Abstract:
Standard-of-care influenza virus vaccines are composed of a mixture of antigens from different influenza viral subtypes. For the first time, lead COBRA H1 and H3 HA antigens, formulated as a bivalent vaccine, have been investigated in animals with preexisting immunity to influenza viruses. ABSTRACT Commercial influenza virus vaccines often elicit strain-specific immune responses and have difficulties preventing illness caused by antigenically drifted viral variants. In the last 20 years, the H3N2 component of the annual vaccine has been updated nearly twice as often as the H1N1 component, and in 2019, a mismatch between the wild-type (WT) H3N2 vaccine strain and circulating H3N2 influenza strains led to a vaccine efficacy of ∼9%. Modern methods of developing computationally optimized broadly reactive antigens (COBRAs) for H3N2 influenza viruses utilize current viral surveillance information to design more broadly reactive vaccine antigens. Here, 7 new recombinant hemagglutinin (rHA) H3 COBRA hemagglutinin (HA) antigens were evaluated in mice. Subsequently, two candidates, J4 and NG2, were selected for further testing in influenza-preimmune animals based on their ability to elicit broadly reactive antibodies against antigenically drifted H3N2 viral isolates. In the preimmune model, monovalent formulations of J4 and NG2 elicited broadly reactive antibodies against recently circulating H3N2 influenza viruses from 2019. Bivalent mixtures of COBRA H1 and H3 rHA, Y2 + J4, and Y2 + NG2 outperformed multiple WT H1+H3 bivalent rHA mixtures by eliciting seroprotective antibodies against H1N1 and H3N2 isolates from 2009 to 2019. Overall, the newly generated COBRA HA antigens, namely, Y2, J4, and NG2, had the ability to induce broadly reactive antibodies in influenza-naive and preimmune animals in both monovalent and bivalent formulations, and these antigens outperformed H1 and H3 WT rHA vaccine antigens by eliciting seroprotective antibodies against panels of antigenically drifted historical H1N1 and H3N2 vaccine strains from 2009 to 2019. IMPORTANCE Standard-of-care influenza virus vaccines are composed of a mixture of antigens from different influenza viral subtypes. For the first time, lead COBRA H1 and H3 HA antigens, formulated as a bivalent vaccine, have been investigated in animals with preexisting immunity to influenza viruses. The cocktail of COBRA HA antigens elicited more broadly reactive anti-HA antibodies than those elicited by a comparator bivalent wild-type HA vaccine against H1 and H3 influenza viruses isolated between 2009 and 2019.read more
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Computational design of vaccine immunogens.
TL;DR: Computational protein engineering has enabled the rational design of customized proteins, which has propelled both sequence-based and structure-based immunogen engineering and delivery as discussed by the authors , which has driven both sequence based and structure based immunogen development and delivery.
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Differential Recognition of Computationally Optimized H3 Hemagglutinin Influenza Vaccine Candidates by Human Antibodies
TL;DR: Overall, these studies determined that COBRA H3 HA proteins have correct antigenic and structural features, and the proteins are recognized by B cells and monoclonal antibodies isolated from seasonally vaccinated humans.
Journal ArticleDOI
Kinetic of the Antibody Response Following AddaVax-Adjuvanted Immunization with Recombinant Influenza Antigens
Ted M. Ross,Naveen Gokanapudi,Pan Ge,Hua Shi,Robert A. Richardson,Spencer R. Pierce,P. Sanchez,Subhan Ullah,Eliana De Luca,Giuseppe A. Sautto +9 more
TL;DR: The monitoring and characterization of the antibody response associated with the administration of adjuvanted vaccines has been evaluated in this study in order to shed light on the kinetic, magnitude and subclass usage of antibody secreting cells (ASCs) as well as of circulating antigen-specific serum antibodies.
Journal ArticleDOI
Evaluation of Pre-Pandemic Trivalent COBRA HA Vaccine in Mice Pre-Immune to Historical H1N1 and H3N2 Influenza Viruses
Pan Ge,Ted M. Ross +1 more
TL;DR: In this article , the effect of pre-immunization on pre-pandemic influenza virus vaccination was explored in mice that were pre-immune to historical H1N1 and H3N2 seasonal influenza viruses.
Journal ArticleDOI
Recombinant Protein Vaccines Formulated with Enantio-Specific Cationic Lipid R-DOTAP Induce Protective Cellular and Antibody-Mediated Immune Responses in Mice
Siva K. Gandhapudi,Hua Shi,Martin Ward,John Peyton C Bush,Margarita G. Avdiushko,Karuna Sundarapandiyan,Lauren V. Wood,Mania Dorrani,Afsheen Fatima,Joe J. Dervan,Frank K. Bedu-Addo,Greg Conn,Ted M. Ross,Jerold G. Woodward +13 more
TL;DR: In this paper , a pure enantio-specific cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (R-DOTAP) was used as an immunomodulator for subunit vaccines capable of inducing both humoral and cellular-mediated immunity.
References
More filters
Journal ArticleDOI
Estimates of global seasonal influenza-associated respiratory mortality: a modelling study
A. Danielle Iuliano,Katherine Roguski,Howard H. Chang,David Muscatello,Rakhee Palekar,Stefano Tempia,Cheryl Cohen,Jon Michael Gran,Jon Michael Gran,Dena L. Schanzer,Benjamin J. Cowling,Peng Wu,Jan Kynčl,Li Wei Ang,Minah Park,Monika Redlberger-Fritz,Hongjie Yu,Laura Espenhain,Anand Krishnan,Gideon O. Emukule,Liselotte van Asten,Susana Silva,Suchunya Aungkulanon,Udo Buchholz,Marc-Alain Widdowson,Joseph S. Bresee,Eduardo Azziz-Baumgartner,Po-Yung Cheng,Fatimah S. Dawood,Ivo M. Foppa,Sonja J. Olsen,Michael Haber,Caprichia Jeffers,C. Raina MacIntyre,Anthony T. Newall,James G. Wood,Michael Kundi,Therese Popow-Kraupp,Makhdum Ahmed,Mahmudur Rahman,Fatima Marinho,C Viviana Sotomayor Proschle,Natalia Vergara Mallegas,Feng Luzhao,Li Sa,Juliana Barbosa-Ramírez,Diana Malo Sanchez,Leandra Abarca Gomez,Xiomara Badilla Vargas,aBetsy Acosta Herrera,María Josefa Llanés,Thea Kølsen Fischer,Tyra Grove Krause,Kåre Mølbak,Jens Nielsen,Ramona Trebbien,Alfredo Bruno,Jenny Ojeda,Hector Ramos,Matthias an der Heiden,Leticia del Carmen Castillo Signor,Carlos Enrique Serrano,Rohit Bhardwaj,Mandeep S. Chadha,Venkatesh Vinayak Narayan,Soewarta Kosen,Michal Bromberg,Aharona Glatman-Freedman,Zalman Kaufman,Yuzo Arima,Kazunori Oishi,Sandra S. Chaves,Bryan O. Nyawanda,Reem Abdullah Al-Jarallah,Pablo A Kuri-Morales,Cuitláhuac Ruiz Matus,Maria Eugenia Jimenez Corona,Alexander Burmaa,Oyungerel Darmaa,Majdouline Obtel,Imad Cherkaoui,Cees C van den Wijngaard,Wim van der Hoek,Michael G Baker,Don Bandaranayake,Ange Bissielo,Sue Huang,Liza Lopez,Claire Newbern,Elmira Flem,Gry M Grøneng,Siri Hauge,Federico G de Cosío,Yadira De Molto,Lourdes Moreno Castillo,María Agueda Cabello,Marta Von Horoch,José L. Medina Osis,Ausenda Machado,Baltazar Nunes,Ana Paula Rodrigues,Emanuel Rodrigues,Cristian Calomfirescu,Emilia Lupulescu,Rodica Popescu,Odette Popovici,Dragan Bogdanovic,Marina Kostic,Konstansa Lazarevic,Zoran Milosevic,Branislav Tiodorovic,Mark I-Cheng Chen,Jeffery Cutter,Vernon J. Lee,Raymond T. P. Lin,Stefan Ma,Adam L. Cohen,Florette K. Treurnicht,Woo Joo Kim,Concha Delgado-Sanz,Salvador de mateo Ontañón,Amparo Larrauri,Inmaculada León,Fernando Vallejo,Rita Born,Christoph Junker,Daniel Koch,Jen-Hsiang Chuang,Wan-Ting Huang,Hung-Wei Kuo,Yi-Chen Tsai,Kanitta Bundhamcharoen,Malinee Chittaganpitch,Helen K. Green,Richard Pebody,Natalia Goñi,Hector Chiparelli,Lynnette Brammer,Desiree Mustaquim +138 more
TL;DR: These global influenza-associated respiratory mortality estimates are higher than previously reported, suggesting that previous estimates might have underestimated disease burden.
Journal ArticleDOI
Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices - United States, 2020-21 Influenza Season.
Lisa A. Grohskopf,Leslie Z. Sokolow,Leslie Z. Sokolow,Sonja J. Olsen,Joseph S. Bresee,Karen R. Broder,Ruth A. Karron +6 more
TL;DR: This report updates the 2017–18 recommendations of the Advisory Committee on Immunization Practices regarding the use of seasonal influenza vaccines in the United States and focuses on the recommendations for use of vaccines for the prevention and control of influenza during the 2018–19 season.
Journal ArticleDOI
Considerations for formulating the second-generation pneumococcal capsular polysaccharide vaccine with emphasis on the cross-reactive types within groups.
JohnB Robbins,Robert Austrian,Lee Cj,Suresh C. Rastogi,Gerald Schiffman,J. Henrichsen,P. H. Mäkelä,Claire V. Broome,Richard R. Facklam,Tiesjema Rh +9 more
Journal ArticleDOI
New low-viscosity overlay medium for viral plaque assays
TL;DR: Plaque assay under Avicel-containing overlay media is easier, faster and more sensitive than assays under agar- and methylcellulose overlays and seems particularly suitable for high-throughput virus titrations, serological studies and experiments on viral drug sensitivity.
Journal ArticleDOI
Potent protection against H5N1 and H7N9 influenza via childhood hemagglutinin imprinting.
TL;DR: Using data from all known human cases of these viruses, it is shown that an individual’s first IAV infection confers lifelong protection against severe disease from novel hemagglutinin (HA) subtypes in the same phylogenetic group, and statistical modeling shows that protective HA imprinting is the crucial explanatory factor.