Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses

Main text

(Immunity 54, 2877–2892.e1–e7, December 14, 2021)

Due to an oversight, two authors were omitted from the author list. The author list, the author contribution section, and the acknowledgments have been updated and corrected online and in print. The authors apologize for the error.

Original text:

Mohamad-Gabriel Alameh,^1,9 István Tombácz,^1,9 Emily Bettini,^2,9 Katlyn Lederer,² Chutamath Sittplangkoon,³ Joel R. Wilmore,⁴ Brian T. Gaudette,⁴ Ousamah Y. Soliman,¹ Matthew Pine,¹ Philip Hicks,^2,5 Tomaz B. Manzoni,² James J. Knox,⁴ John L. Johnson,⁴ Dorottya Laczkó,¹ Hiromi Muramatsu,¹ Benjamin Davis,¹ Wenzhao Meng,⁴ Aaron M. Rosenfeld,⁴ Shirin Strohmeier,⁶ Paulo J.C. Lin,⁷ Barbara L. Mui,⁷ Ying K. Tam,⁷ Katalin Karikó,^1,8 Alain Jacquet,³ Florian Krammer,⁶ Paul Bates,² Michael P. Cancro,⁴ Drew Weissman,¹ Eline T. Luning Prak,⁴ David Allman,⁴ Michela Locci,² and Norbert Pardi^1,10

¹Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA

²Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

³Center of Excellence in Vaccine Research and Development, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

⁴Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

⁵School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA

⁶Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

⁷Acuitas Therapeutics, Vancouver, BC, Canada

⁸BioNTech RNA Pharmaceuticals, Mainz, Germany

⁹These authors contributed equally

¹⁰Lead Contact

Corrected text:

Mohamad-Gabriel Alameh,^1,10 István Tombácz,^1,10 Emily Bettini,^2,10 Katlyn Lederer,² Sonia Ndeupen,³ Chutamath Sittplangkoon,⁴ Joel R. Wilmore,⁵ Brian T. Gaudette,⁵ Ousamah Y. Soliman,¹ Matthew Pine,¹ Philip Hicks,^2,6 Tomaz B. Manzoni,² James J. Knox,⁵ John L. Johnson,⁵ Dorottya Laczkó,¹ Hiromi Muramatsu,¹ Benjamin Davis,¹ Wenzhao Meng,⁵ Aaron M. Rosenfeld,⁵ Shirin Strohmeier,⁷ Paulo J.C. Lin,⁸ Barbara L. Mui,⁸ Ying K. Tam,⁸ Katalin Karikó,^1,9 Alain Jacquet,⁴ Florian Krammer,⁷ Paul Bates,² Michael P. Cancro,⁵ Drew Weissman,¹ Eline T. Luning Prak,⁵ David Allman,⁵ Botond Z. Igyártó,³ Michela Locci,² and Norbert Pardi^1,11

¹Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA

²Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

³Thomas Jefferson University, Department of Microbiology and Immunology, Philadelphia, PA, USA

⁴Center of Excellence in Vaccine Research and Development, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

⁵Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

⁶School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA

⁷Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA

⁸Acuitas Therapeutics, Vancouver, BC, Canada

⁹BioNTech RNA Pharmaceuticals, Mainz, Germany

¹⁰These authors contributed equally

¹¹Lead contact

Original text:

Acknowledgments

N.P. was supported by the National Institute of Allergy and Infectious Diseases (NIAID, R01AI146101 and R01AI153064). M.L. was supported by NIAID (R01AI123738 and R01AI153064). D.W. is supported by NIH/NIAID (UM1-AI-144371, 1U19AI135902, U19-AI142596, R01-AI124429, HHS-NIH-NIAID-BAA2018) and an SRA from BioNTech. E.L.P., W.M., J.K.K., and A.M.R. were supported by P01 AI106697. F.K. was supported by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051. D.A. was supported by NIAID (R01AI139123 and R01AI154932). We thank the NIH Tetramer Core Facility for producing the I-A(d) Influenza A HA PE-conjugated tetramer (HNTNGVTAACSHE) used in this study and the Human Immunology Core facility for assistance with immunoglobulin gene rearrangement sequencing (with infrastructure support from P30 CA016520 and P30-AI 0450080). We thank Dr. Florin Tuluc and Jennifer Murray of the Children’s Hospital of Philadelphia (CHOP) Flow Cytometry core facility for technical assistance. PR8 HA probes for initial LLPC and MBC studies were provided by Scott E. Hensley (University of Pennsylvania). Mouse-adapted A/Puerto Rico/8/1934 influenza virus for challenge studies was provided by Michael J. Hogan and Laurence C. Eisenlohr (CHOP). We thank Michael J. Hogan for the critical reading of the manuscript. The graphical abstract was created with BioRender.

Corrected text:

Acknowledgments

N.P. was supported by the National Institute of Allergy and Infectious Diseases (NIAID, R01AI146101 and R01AI153064). M.L. was supported by NIAID (R01AI123738 and R01AI153064). D.W. is supported by NIH/NIAID (UM1-AI-144371, 1U19AI135902, U19-AI142596, R01-AI124429, HHS-NIH-NIAID-BAA2018) and an SRA from BioNTech. E.L.P., W.M., J.K.K., and A.M.R. were supported by P01 AI106697. F.K. was supported by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051. D.A. was supported by NIAID (R01AI139123 and R01AI154932). The Igyártó lab is supported by NIAID (R01AI146420 and R01AI146101). We thank the NIH Tetramer Core Facility for producing the I-A(d) Influenza A HA PE-conjugated tetramer (HNTNGVTAACSHE) used in this study and the Human Immunology Core facility for assistance with immunoglobulin gene rearrangement sequencing (with infrastructure support from P30 CA016520 and P30-AI 0450080). We thank Dr. Florin Tuluc and Jennifer Murray of the Children’s Hospital of Philadelphia (CHOP) Flow Cytometry core facility for technical assistance. PR8 HA probes for initial LLPC and MBC studies were provided by Scott E. Hensley (University of Pennsylvania). Mouse-adapted A/Puerto Rico/8/1934 influenza virus for challenge studies was provided by Michael J. Hogan and Laurence C. Eisenlohr (CHOP). We thank Michael J. Hogan for the critical reading of the manuscript. The graphical abstract was created with BioRender.

Original text:

Author contributions

N.P. and M.L. conceptualized the study. M.L, D.A. and M.P.C. designed B cell studies. N.P, M.L., M.G.A, I.T., and E.B. wrote the paper with help from co-authors. I.T., E.B., and K.L. graphed data and produced figures. H.M. produced mRNA vaccine antigens. Y.K.T., B.L.M., and P.J.C.L. produced empty LNP and encapsulated mRNAs into LNP and performed the physicochemical characterization of LNP. N.P., M.G.A., I.T., K.L., C.S., E.B., and A.J. performed immunizations. K.K. designed the untranslated region of the mRNA. D.L., M.G.A., M.P., B.D., and I.T. performed HAI assays. M.G.A., E.B., O.S., and I.T. performed ELISAs. M.L., K.L., D.A., J.R.W., M.G.A, E.B., and B.T.G. performed Tfh and B cell flow cytometry analyses. M.G.A designed and performed, M.G.A. and I.T. analyzed the Luminex assay. E.T.L.P., W.M., A.M.R., M.P.C., J.J.K., and J.L.J. performed B cell sorting and B cell receptor sequencing experiments and analyzed the immune repertoire profiling data. P.B., P.H., and T.B.M performed pseudovirus neutralization assays. F.K. and S.S. produced recombinant PR8 HA and RBD proteins used to produce fluorescently labeled probes. M.L., M.G.A, E.B., and K.L., produced fluorescently labeled probes. I.T. and N.P. performed challenge studies.

Corrected text:

Author contributions

N.P., M.L., and B.Z.I. conceptualized the study. M.L, D.A., and M.P.C. designed B cell studies. N.P, M.L., M.G.A, I.T., and E.B. wrote the paper with help from co-authors. I.T., E.B., and K.L. graphed data and produced figures. H.M. produced mRNA vaccine antigens. Y.K.T., B.L.M., and P.J.C.L. produced empty LNP and encapsulated mRNAs into LNP and performed the physicochemical characterization of LNP. N.P., M.G.A., I.T., K.L., S.N., C.S., E.B., and A.J. performed immunizations. S.N. and B.Z.I. contributed to the design of studies investigating the inflammatory properties of lipid nanoparticles. K.K. designed the untranslated region of the mRNA. D.L., M.G.A., M.P., B.D., and I.T. performed HAI assays. M.G.A., E.B., O.S., and I.T. performed ELISAs. M.L., K.L., D.A., J.R.W., M.G.A, E.B., and B.T.G. performed Tfh and B cell flow cytometry analyses. M.G.A designed and performed, M.G.A. and I.T. analyzed the Luminex assay. E.T.L.P., W.M., A.M.R., M.P.C., J.J.K., and J.L.J. performed B cell sorting and B cell receptor sequencing experiments and analyzed the immune repertoire profiling data. P.B., P.H., and T.B.M performed pseudovirus neutralization assays. F.K. and S.S. produced recombinant PR8 HA and RBD proteins used to produce fluorescently labeled probes. M.L., M.G.A, E.B., and K.L., produced fluorescently labeled probes. I.T. and N.P. performed challenge studies.