Transcriptome signatures preceding the induction of anti-stalk antibodies elicited after universal influenza vaccination by Teresa Aydillo, Ana S. Gonzalez-Reiche, Daniel Stadlbauer, Mary Anne Amper, Venugopalan D. Nair, Chiara Mariottini, Stuart C. Sealfon, Harm van Bakel, Peter Palese, Florian Krammer, Adolfo García-Sastre

“…Abstract A phase 1 clinical trial to test the immunogenicity of a chimeric group 1 HA (cHA) universal influenza virus vaccine targeting the conserved stalk domain of the hemagglutinin of influenza viruses was carried out. …”
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An Inactivated Influenza Virus Vaccine Approach to Targeting the Conserved Hemagglutinin Stalk and M2e Domains by Weina Sun, Allen Zheng, Robert Miller, Florian Krammer, Peter Palese

“…Sequential immunization with inactivated viruses containing these modified cHAs substantially enhanced M2e antibody responses while simultaneously boosting stalk antibody responses. The combination of additional M2e antibodies with HA stalk antibodies resulted in superior antibody-mediated protection in mice against challenge viruses expressing homologous or heterosubtypic hemagglutinin and neuraminidase compared to vaccination strategies that targeted the HA stalk or M2e epitopes in isolation.…”
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A carboxy-terminal trimerization domain stabilizes conformational epitopes on the stalk domain of soluble recombinant hemagglutinin substrates. by Florian Krammer, Irina Margine, Gene S Tan, Natalie Pica, Jens C Krause, Peter Palese

“…Recently, a new class of broadly neutralizing anti-influenza virus antibodies that target the stalk domain of the viral hemagglutinin was discovered. …”
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Introduction of Cysteines in the Stalk Domain of Recombinant Influenza Virus N1 Neuraminidase Enhances Protein Stability and Immunogenicity in Mice by Shirin Strohmeier, Juan Manuel Carreño, Ruhi Nichalle Brito, Florian Krammer

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Development and Assessment of a Pooled Serum as Candidate Standard to Measure Influenza A Virus Group 1 Hemagglutinin Stalk-Reactive Antibodies by Juan Manuel Carreño, Jacqueline U. McDonald, Tara Hurst, Peter Rigsby, Eleanor Atkinson, Lethia Charles, Raffael Nachbagauer, Mohammad Amin Behzadi, Shirin Strohmeier, Lynda Coughlan, Teresa Aydillo, Boerries Brandenburg, Adolfo García-Sastre, Krisztian Kaszas, Min Z. Levine, Alessandro Manenti, Adrian B. McDermott, Emanuele Montomoli, Leacky Muchene, Sandeep R. Narpala, Ranawaka A. P. M. Perera, Nadine C. Salisch, Sophie A. Valkenburg, Fan Zhou, Othmar G. Engelhardt, Florian Krammer

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Bioprocess development for universal influenza vaccines based on inactivated split chimeric and mosaic hemagglutinin viruses by Eduard Puente-Massaguer, Annika Beyer, Madhumathi Loganathan, Iden Sapse, Juan Manuel Carreño, Juan Manuel Carreño, Goran Bajic, Weina Sun, Peter Palese, Peter Palese, Florian Krammer, Florian Krammer, Florian Krammer

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Chimeric Hemagglutinin-Based Live-Attenuated Vaccines Confer Durable Protective Immunity against Influenza A Viruses in a Preclinical Ferret Model by Wen-Chun Liu, Raffael Nachbagauer, Daniel Stadlbauer, Shirin Strohmeier, Alicia Solórzano, Francesco Berlanda-Scorza, Bruce L. Innis, Adolfo García-Sastre, Peter Palese, Florian Krammer, Randy A. Albrecht

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A Universal Influenza Virus Vaccine Candidate Tested in a Pig Vaccination-Infection Model in the Presence of Maternal Antibodies by Sun-Young Sunwoo, Michael Schotsaert, Igor Morozov, Anne Sally Davis, Yuhao Li, Jinhwa Lee, Chester McDowell, Philip Meade, Raffael Nachbagauer, Adolfo García-Sastre, Wenjun Ma, Florian Krammer, Juergen A. Richt

“…The antigenically conserved hemagglutinin stalk region is a target for universal influenza virus vaccines since antibodies against it can provide broad protection against influenza viruses of different subtypes. …”
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Broad cross-reactive IgG responses elicited by adjuvanted vaccination with recombinant influenza hemagglutinin (rHA) in ferrets and mice. by Jiong Wang, Shannon P Hilchey, Marta DeDiego, Sheldon Perry, Ollivier Hyrien, Aitor Nogales, Jessica Garigen, Fatima Amanat, Nelson Huertas, Florian Krammer, Luis Martinez-Sobrido, David J Topham, John J Treanor, Mark Y Sangster, Martin S Zand

“…We have also found that adjuvant plays a critical role in the generation of long-lived ASCs and MBCs cross-reactive to influenza viruses as a result of vaccination with rHA of influenza virus, and the observed increase in stalk-reactive antibodies likely contributes to this IgG mediated broad cross-reactivity.…”
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No evidence of antigenic seniority in hemagglutinin specific antibody responses after adjuvanted pandemic 2009 influenza vaccination by Anders Madsen, Linda Azimi, Sarah Tete, Fan Zhou, Florian Krammer, Rebecca Jane Cox, Åsne Jul-Larsen

“…We found that the more antigenically experienced individuals had higher pre-vaccination antibody-levels towards the stalk domain of the HA. We also demonstrated that despite their inferior pre-vaccination antibody levels, the younger individuals reached similar antibody levels as the older birth-cohorts after pandemic vaccination. …”
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A Live-Attenuated Prime, Inactivated Boost Vaccination Strategy with Chimeric Hemagglutinin-Based Universal Influenza Virus Vaccines Provides Protection in Ferrets: A Confirmatory... by Raffael Nachbagauer, Florian Krammer, Randy A. Albrecht

“…Novel influenza virus vaccines that aim to elicit antibodies against conserved epitopes like the hemagglutinin stalk could not only reduce the burden of drifted seasonal viruses but potentially also protect humans from infection with zoonotic and emerging pandemic influenza viruses. …”
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Enhancing the protection of influenza virus vaccines with BECC TLR4 adjuvant in aged mice by Robert Haupt, Lauren Baracco, Erin M. Harberts, Madhumathi Loganathan, Lucas J. Kerstetter, Florian Krammer, Lynda Coughlan, Robert K. Ernst, Matthew B. Frieman

“…In this study, we determined that immunization with HA + BECC adjuvants also significantly broadened the epitopes targeted on HA as compared with other adjuvants, resulting in increased titers of antibodies directed against the highly conserved HA stalk domain. Importantly, we demonstrate that BECC470 combined with an influenza virus HA protein antigen in a prime-only immunization regimen was able to achieve complete protection from challenge in a ~ 12-month-old mouse aged model. …”
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The antibody landscapes following AS03 and MF59 adjuvanted H5N1 vaccination by Johannes B. Goll, Aarti Jain, Travis L. Jensen, Rafael Assis, Rie Nakajima, Algis Jasinskas, Lynda Coughlan, Sami R. Cherikh, Casey E. Gelber, S. Khan, D. Huw Davies, Philip Meade, Daniel Stadlbauer, Shirin Strohmeier, Florian Krammer, Wilbur H. Chen, Philip L. Felgner

“…The adjuvanted vaccine was also associated with the elicitation of stalk-directed antibody. We established good correlation of the array antibody responses to H5 antigens with standard HA inhibition and microneutralization titers.…”
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Persistently high antibody responses after AS03-adjuvanted H1N1pdm09 vaccine: Dissecting the HA specific antibody response by Anders Madsen, Åsne Jul-Larsen, Mai-Chi Trieu, Florian Krammer, Rebecca J. Cox

“…All groups had similar levels of antibodies towards the conserved HA stalk domain. The level of HA head-specific antibodies gradually increased over time with annual vaccination in the transient responders. …”
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