A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial

doi:10.1038/s41591-020-1118-7

Clinical Trial

. 2021 Jan;27(1):106-114.

doi: 10.1038/s41591-020-1118-7. Epub 2020 Dec 7.

A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial

Raffael Nachbagauer^{1

2}, Jodi Feser³, Abdollah Naficy³, David I Bernstein^{4

5}, Jeffrey Guptill⁶, Emmanuel B Walter^{6

7}, Franceso Berlanda-Scorza^{3

8}, Daniel Stadlbauer¹, Patrick C Wilson^{9

10}, Teresa Aydillo^{1

11}, Mohammad Amin Behzadi¹, Disha Bhavsar¹, Carly Bliss¹, Christina Capuano¹, Juan Manuel Carreño¹, Veronika Chromikova¹, Carine Claeys^{12

13}, Lynda Coughlan¹, Alec W Freyn^{1

14}, Christopher Gast³, Andres Javier¹, Kaijun Jiang¹, Chiara Mariottini¹, Meagan McMahon¹, Monica McNeal^{4

5}, Alicia Solórzano^{1

15}, Shirin Strohmeier^{1

16}, Weina Sun¹, Marie Van der Wielen¹², Bruce L Innis³, Adolfo García-Sastre^{1

11

17

18}, Peter Palese^{1

17

18}, Florian Krammer¹⁹

Affiliations

¹ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
² Moderna, Cambridge, MA, USA.
³ Center for Vaccine Innovation and Access, PATH, Seattle, WA, USA.
⁴ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
⁵ Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁶ Duke Early Phase Clinical Research Unit, Duke Clinical Research Institute, Durham, NC, USA.
⁷ Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
⁸ GSK, Siena, Italy.
⁹ Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, IL, USA.
¹⁰ The Committee on Immunology, University of Chicago, Chicago, IL, USA.
¹¹ Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹² GSK, Wavre, Belgium.
¹³ Spmt-Arista Asbl, Brussels, Belgium.
¹⁴ Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁵ Pfizer, Pearl River, NY, USA.
¹⁶ Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria.
¹⁷ Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁸ The Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁹ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. florian.krammer@mssm.edu.

PMID: 33288923
DOI: 10.1038/s41591-020-1118-7

Clinical Trial

A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial

Raffael Nachbagauer et al. Nat Med. 2021 Jan.

. 2021 Jan;27(1):106-114.

doi: 10.1038/s41591-020-1118-7. Epub 2020 Dec 7.

Authors

Affiliations

¹ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
² Moderna, Cambridge, MA, USA.
³ Center for Vaccine Innovation and Access, PATH, Seattle, WA, USA.
⁴ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
⁵ Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁶ Duke Early Phase Clinical Research Unit, Duke Clinical Research Institute, Durham, NC, USA.
⁷ Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
⁸ GSK, Siena, Italy.
⁹ Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, IL, USA.
¹⁰ The Committee on Immunology, University of Chicago, Chicago, IL, USA.
¹¹ Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹² GSK, Wavre, Belgium.
¹³ Spmt-Arista Asbl, Brussels, Belgium.
¹⁴ Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁵ Pfizer, Pearl River, NY, USA.
¹⁶ Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria.
¹⁷ Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁸ The Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹⁹ Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA. florian.krammer@mssm.edu.

PMID: 33288923
DOI: 10.1038/s41591-020-1118-7

Abstract

Seasonal influenza viruses constantly change through antigenic drift and the emergence of pandemic influenza viruses through antigenic shift is unpredictable. Conventional influenza virus vaccines induce strain-specific neutralizing antibodies against the variable immunodominant globular head domain of the viral hemagglutinin protein. This necessitates frequent re-formulation of vaccines and handicaps pandemic preparedness. In this completed, observer-blind, randomized, placebo-controlled phase I trial (NCT03300050), safety and immunogenicity of chimeric hemagglutinin-based vaccines were tested in healthy, 18-39-year-old US adults. The study aimed to test the safety and ability of the vaccines to elicit broadly cross-reactive antibodies against the hemagglutinin stalk domain. Participants were enrolled into five groups to receive vaccinations with live-attenuated followed by AS03-adjuvanted inactivated vaccine (n = 20), live-attenuated followed by inactivated vaccine (n = 15), twice AS03-adjuvanted inactivated vaccine (n = 16) or placebo (n = 5, intranasal followed by intramuscular; n = 10, twice intramuscular) 3 months apart. Vaccination was found to be safe and induced a broad, strong, durable and functional immune response targeting the conserved, immunosubdominant stalk of the hemagglutinin. The results suggest that chimeric hemagglutinins have the potential to be developed as universal vaccines that protect broadly against influenza viruses.

PubMed Disclaimer

Cited by

The antibody landscapes following AS03 and MF59 adjuvanted H5N1 vaccination.
Goll JB, Jain A, Jensen TL, Assis R, Nakajima R, Jasinskas A, Coughlan L, Cherikh SR, Gelber CE, Khan S, Huw Davies D, Meade P, Stadlbauer D, Strohmeier S, Krammer F, Chen WH, Felgner PL. Goll JB, et al. NPJ Vaccines. 2022 Aug 30;7(1):103. doi: 10.1038/s41541-022-00524-7. NPJ Vaccines. 2022. PMID: 36042229 Free PMC article.
ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies.
Low JS, Jerak J, Tortorici MA, McCallum M, Pinto D, Cassotta A, Foglierini M, Mele F, Abdelnabi R, Weynand B, Noack J, Montiel-Ruiz M, Bianchi S, Benigni F, Sprugasci N, Joshi A, Bowen JE, Stewart C, Rexhepaj M, Walls AC, Jarrossay D, Morone D, Paparoditis P, Garzoni C, Ferrari P, Ceschi A, Neyts J, Purcell LA, Snell G, Corti D, Lanzavecchia A, Veesler D, Sallusto F. Low JS, et al. Science. 2022 Aug 12;377(6607):735-742. doi: 10.1126/science.abq2679. Epub 2022 Jul 12. Science. 2022. PMID: 35857703 Free PMC article.
Single-Cell Transcriptome Analysis of H5N1-HA-Stimulated Alpaca PBMCs.
Lyu M, Shi X, Liu Y, Zhao H, Yuan Y, Xie R, Gu Y, Dong Y, Wang M. Lyu M, et al. Biomolecules. 2022 Dec 28;13(1):60. doi: 10.3390/biom13010060. Biomolecules. 2022. PMID: 36671445 Free PMC article.
Genomics serology to inform therapies and vaccines for arthritogenic alphaviruses.
García-Sastre A. García-Sastre A. Proc Natl Acad Sci U S A. 2021 Oct 12;118(41):e2114687118. doi: 10.1073/pnas.2114687118. Proc Natl Acad Sci U S A. 2021. PMID: 34625494 Free PMC article. No abstract available.
A Review on Equine Influenza from a Human Influenza Perspective.
Whitlock F, Murcia PR, Newton JR. Whitlock F, et al. Viruses. 2022 Jun 15;14(6):1312. doi: 10.3390/v14061312. Viruses. 2022. PMID: 35746783 Free PMC article. Review.

See all "Cited by" articles

References

1. Palese, P. Influenza: old and new threats. Nat. Med. 10, S82–S87 (2004). - PubMed
1. Chan, M. C. W. et al. Frequent genetic mismatch between vaccine strains and circulating seasonal influenza viruses, Hong Kong, China, 1996–2012. Emerg. Infect. Dis. 24, 1825–1834 (2018). - PubMed - PMC
1. Flannery, B. et al. Spread of antigenically drifted influenza A(H3N2) viruses and vaccine effectiveness in the United States during the 2018–2019 season. J. Infect. Dis. 221, 8–15 (2020). - PubMed
1. Skowronski, D. M. et al. Paradoxical clade- and age-specific vaccine effectiveness during the 2018/19 influenza A(H3N2) epidemic in Canada: potential imprint-regulated effect of vaccine (I-REV). Euro Surveill. 24, 1900585 (2019). - PMC
1. Owusu, D. et al. Early season pediatric influenza B/Victoria virus infections associated with a recently emerged virus subclade—Louisiana, 2019. MMWR Morb. Mortal. Wkly Rep. 69, 40–43 (2020). - PubMed - PMC

Publication types

Actions
Actions
Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions

Associated data

Actions
- Search in PubMed
- Search in ClinicalTrials.gov

Grants and funding

LinkOut - more resources

Full Text Sources
- Nature Publishing Group
Other Literature Sources
- H1 Connect
Medical
- MedlinePlus Health Information

[1] Palese, P. Influenza: old and new threats. Nat. Med. 10, S82–S87 (2004). - PubMed

[2] Palese, P. Influenza: old and new threats. Nat. Med. 10, S82–S87 (2004). - PubMed

[3] Chan, M. C. W. et al. Frequent genetic mismatch between vaccine strains and circulating seasonal influenza viruses, Hong Kong, China, 1996–2012. Emerg. Infect. Dis. 24, 1825–1834 (2018). - PubMed - PMC

[4] Chan, M. C. W. et al. Frequent genetic mismatch between vaccine strains and circulating seasonal influenza viruses, Hong Kong, China, 1996–2012. Emerg. Infect. Dis. 24, 1825–1834 (2018). - PubMed - PMC

[5] Flannery, B. et al. Spread of antigenically drifted influenza A(H3N2) viruses and vaccine effectiveness in the United States during the 2018–2019 season. J. Infect. Dis. 221, 8–15 (2020). - PubMed

[6] Flannery, B. et al. Spread of antigenically drifted influenza A(H3N2) viruses and vaccine effectiveness in the United States during the 2018–2019 season. J. Infect. Dis. 221, 8–15 (2020). - PubMed

[7] Skowronski, D. M. et al. Paradoxical clade- and age-specific vaccine effectiveness during the 2018/19 influenza A(H3N2) epidemic in Canada: potential imprint-regulated effect of vaccine (I-REV). Euro Surveill. 24, 1900585 (2019). - PMC

[8] Skowronski, D. M. et al. Paradoxical clade- and age-specific vaccine effectiveness during the 2018/19 influenza A(H3N2) epidemic in Canada: potential imprint-regulated effect of vaccine (I-REV). Euro Surveill. 24, 1900585 (2019). - PMC

[9] Owusu, D. et al. Early season pediatric influenza B/Victoria virus infections associated with a recently emerged virus subclade—Louisiana, 2019. MMWR Morb. Mortal. Wkly Rep. 69, 40–43 (2020). - PubMed - PMC

[10] Owusu, D. et al. Early season pediatric influenza B/Victoria virus infections associated with a recently emerged virus subclade—Louisiana, 2019. MMWR Morb. Mortal. Wkly Rep. 69, 40–43 (2020). - PubMed - PMC

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial

Affiliations

A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial

Authors

Affiliations

Abstract

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Abstract

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Associated data

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical