Nucleoside-modified mRNA immunization elicits influenza virus hemagglutinin stalk-specific antibodies

Nature Communications

Volumn 9, Issue 1, 2018, Pages

  Pardi, Norbert ^a   Parkhouse, Kaela ^b   Kirkpatrick, Ericka ^c   McMahon, Meagan ^c   Zost, Seth J ^b   Mui, Barbara L ^d   Tam, Ying K ^d   Karikó, Katalin ^e   Barbosa, Christopher J ^d   Madden, Thomas D ^d   Hope, Michael J ^d   Krammer, Florian ^c   Hensley, Scott E ^b   Weissman, Drew ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^d Acuitas Therapeutics   (Canada)

^e BIONTECH AG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

INFLUENZA VACCINE; LIPID NANOPARTICLE; MESSENGER RNA; NANOPARTICLE; NUCLEOSIDE; RECOMBINANT PROTEIN; UNCLASSIFIED DRUG; VIRUS HEMAGGLUTININ; HEMAGGLUTININ; VIRUS ANTIBODY;

ANTIBODY; ANTIGEN; IMMUNE RESPONSE; IMMUNIZATION; INFLUENZA; LIPID; NANOPARTICLE; NUCLEIC ACID; PROTEIN; RNA; RODENT; VACCINE; VIRUS;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBODY RESPONSE; ARTICLE; CONTROLLED STUDY; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; FLOW CYTOMETRY; IMMUNIZATION; IMMUNOGENICITY; INFLUENZA; INFLUENZA VACCINATION; INFLUENZA VIRUS; LEPORIDAE; MOUSE; MUSTELA PUTORIUS FURO; NONHUMAN; SEASONAL INFLUENZA; SPLEEN CELL; VIRUS STRAIN; ANIMAL; BAGG ALBINO MOUSE; CELL CULTURE; CHEMISTRY; DOG; IMMUNOLOGY; INFLUENZA A VIRUS (H5N1); MDCK CELL LINE; ORTHOMYXOVIRIDAE; PHYLOGENY;

MUS; MUSTELA; ORTHOMYXOVIRIDAE; ORYCTOLAGUS CUNICULUS;

ANIMALS; ANTIBODIES, VIRAL; CELLS, CULTURED; DOGS; ENZYME-LINKED IMMUNOSORBENT ASSAY; FEMALE; FERRETS; FLOW CYTOMETRY; HEMAGGLUTININS; INFLUENZA A VIRUS, H5N1 SUBTYPE; MADIN DARBY CANINE KIDNEY CELLS; MICE; MICE, INBRED BALB C; ORTHOMYXOVIRIDAE; PHYLOGENY; RABBITS; RNA, MESSENGER;

EID: 85052075576     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/s41467-018-05482-0     Document Type: Article

References (49)

1. Krammer, F. & Palese, P. Advances in the development of influenza virus vaccines. Nat. Rev. Drug Discov. 14, 167–182 (2015)
2. Krammer, F. & Palese, P. Influenza virus hemagglutinin stalk-based antibodies and vaccines. Curr. Opin. Virol. 3, 521–530 (2013)
3. Yassine, H. M. et al. Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection. Nat. Med. 21, 1065–1070 (2015)
4. Impagliazzo, A. et al. A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. Science 349, 1301–1306 (2015)
5. Valkenburg, S. A. et al. Stalking influenza by vaccination with pre-fusion headless HA mini-stem. Sci. Rep. 6, 22666 (2016)
6. Ermler, M. E. et al. Chimeric hemagglutinin constructs induce broad protection against influenza B virus challenge in the mouse model. J. Virol. 91, e00286-17 (2017)
7. Nachbagauer, R. et al. A universal influenza virus vaccine candidate confers protection against pandemic H1N1 infection in preclinical ferret studies. NPJ Vaccines 2, 1–13 (2017)
8. Wei, C. J. et al. Induction of broadly neutralizing H1N1 influenza antibodies by vaccination. Science 329, 1060–1064 (2010)
9. Babu, T. M. et al. Live attenuated H7N7 influenza vaccine primes for a vigorous antibody response to inactivated H7N7 influenza vaccine. Vaccine 32, 6798–6804 (2014)
10. Talaat, K. R. et al. A live attenuated influenza A(H5N1) vaccine induces long-term immunity in the absence of a primary antibody response. J. Infect. Dis. 209, 1860–1869 (2014)
11. Halliley, J. L. et al. High-affinity H7 head and stalk domain-specific antibody responses to an inactivated influenza H7N7 vaccine after priming with live attenuated influenza vaccine. J. Infect. Dis. 212, 1270–1278 (2015)
12. Pardi, N., Hogan, M. J., Porter, F. W. & Weissman, D. mRNA vaccines—a new era in vaccinology. Nat. Rev. Drug Discov. 17, 261–279 (2018)
13. Pardi, N. et al. Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes. J. Control Release 217, 345–351 (2015)
14. Pardi, N. et al. Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination. Nature 543, 248–251 (2017)
15. Brazzoli, M. et al. Induction of broad-based immunity and protective efficacy by self-amplifying mRNA vaccines encoding influenza virus hemagglutinin. J. Virol. 90, 332–344 (2015)
16. Magini, D. et al. Self-amplifying mRNA vaccines expressing multiple conserved influenza antigens confer protection against homologous and heterosubtypic viral challenge. PLoS ONE 11, e0161193 (2016)
17. Chahal, J. S. et al. Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose. Proc. Natl Acad. Sci. USA 113, E4133–E4142 (2016)
18. Bahl, K. et al. Preclinical and clinical demonstration of immunogenicity by mRNA vaccines against H10N8 and H7N9 influenza viruses. Mol. Ther. 25, 1316–1327 (2017)
19. Petsch, B. et al. Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nat. Biotechnol. 30, 1210–1216 (2012)
20. Kariko, K. et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16, 1833–1840 (2008)
21. Kariko, K., Muramatsu, H., Ludwig, J. & Weissman, D. Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA. Nucleic Acids Res. 39, e142 (2011)
22. Pica, N. et al. Hemagglutinin stalk antibodies elicited by the 2009 pandemic influenza virus as a mechanism for the extinction of seasonal H1N1 viruses. Proc. Natl Acad. Sci. USA 109, 2573–2578 (2012)
23. Swain, S. L. et al. CD4+ T-cell memory: generation and multi-faceted roles for CD4 +T cells in protective immunity to influenza. Immunol. Rev. 211, 8–22 (2006)
24. Krammer, F., Pica, N., Hai, R., Margine, I. & Palese, P. Chimeric hemagglutinin influenza virus vaccine constructs elicit broadly protective stalk-specific antibodies. J. Virol. 87, 6542–6550 (2013)
25. Krammer, F., Garcia-Sastre, A. & Palese, P. Is it possible to develop a “universal” influenza virus vaccine? Toward a universal influenza virus vaccine: potential target antigens and critical aspects for vaccine development. Cold Spring Harb. Perspect. Biol. 10, a028845 (2017)
26. Andrews, S. F., Graham, B. S., Mascola, J. R. & McDermott, A. B. Is it possible to develop a “universal” influenza virus vaccine? Immunogenetic considerations underlying B-cell biology in the development of a pan-subtype influenza A vaccine targeting the hemagglutinin stem. Cold Spring Harb. Perspect. Biol. 10, a029413 (2017)
27. Krammer, F. Novel universal influenza virus vaccine approaches. Curr. Opin. Virol. 17, 95–103 (2016)
28. Corti, D. et al. Heterosubtypic neutralizing antibodies are produced by individuals immunized with a seasonal influenza vaccine. J. Clin. Invest. 120, 1663–1673 (2010)
29. Sui, J. et al. Wide prevalence of heterosubtypic broadly neutralizing human anti-influenza A antibodies. Clin. Infect. Dis. 52, 1003–1009 (2011)
30. Pardi, N. & Weissman, D. Nucleoside modified mRNA vaccines for infectious diseases. Methods Mol. Biol. 1499, 109–121 (2017)
31. DiLillo, D. J., Tan, G. S., Palese, P. & Ravetch, J. V. Broadly neutralizing hemagglutinin stalk-specific antibodies require FcgammaR interactions for protection against influenza virus in vivo. Nat. Med. 20, 143–151 (2014)
32. Henry Dunand, C. J. et al. Both neutralizing and non-neutralizing human H7N9 influenza vaccine-induced monoclonal antibodies confer protection. Cell Host Microbe 19, 800–813 (2016)
33. Leon, P. E. et al. Optimal activation of Fc-mediated effector functions by influenza virus hemagglutinin antibodies requires two points of contact. Proc. Natl Acad. Sci. USA 113, E5944–E5951 (2016)
34. Terajima, M. et al. Complement-dependent lysis of influenza a virus-infected cells by broadly cross-reactive human monoclonal antibodies. J. Virol. 85, 13463–13467 (2011)
35. Scorza, F. B. & Pardi, N. New kids on the block: RNA-based influenza virus vaccines. Vaccines 6, E20 (2018)
36. Lutz, J. et al. Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines. NPJ Vaccines 2, 1–9 (2017)
37. Li, Y. et al. Immune history shapes specificity of pandemic H1N1 influenza antibody responses. J. Exp. Med. 210, 1493–1500 (2013)
38. Nachbagauer, R. et al. Defining the antibody cross-reactome directed against the influenza virus surface glycoproteins. Nat. Immunol. 18, 464–473 (2017)
39. Zost, S. J. et al. Contemporary H3N2 influenza viruses have a glycosylation site that alters binding of antibodies elicited by egg-adapted vaccine strains. Proc. Natl Acad. Sci. USA 114, 12578–12583 (2017)
40. Wu, N. C. et al. A structural explanation for the low effectiveness of the seasonal influenza H3N2 vaccine. PLoS Pathog. 13, e1006682 (2017)
41. Pardi, N., Muramatsu, H., Weissman, D. & Kariko, K. In vitro transcription of long RNA containing modified nucleosides. Methods Mol. Biol. 969, 29–42 (2013)
42. Thess, A. et al. Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals. Mol. Ther. 23, 1456–1464 (2015)
43. Weissman, D., Pardi, N., Muramatsu, H. & Kariko, K. HPLC purification of in vitro transcribed long RNA. Methods Mol. Biol. 969, 43–54 (2013)
44. Maier, M. A. et al. Biodegradable lipids enabling rapidly eliminated lipid nanoparticles for systemic delivery of RNAi therapeutics. Mol. Ther. 21, 1570–1578 (2013)
45. Jayaraman, M. et al. Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo. Angew. Chem. Int. Ed. Engl. 51, 8529–8533 (2012)
46. Krammer, F. et al. A carboxy-terminal trimerization domain stabilizes conformational epitopes on the stalk domain of soluble recombinant hemagglutinin substrates. PLoS ONE 7, e43603 (2012)
47. Hai, R. et al. Influenza viruses expressing chimeric hemagglutinins: globular head and stalk domains derived from different subtypes. J. Virol. 86, 5774–5781 (2012)
48. Margine, I., Palese, P. & Krammer, F. Expression of functional recombinant hemagglutinin and neuraminidase proteins from the novel H7N9 influenza virus using the baculovirus expression system. J. Vis. Exp. 81, e51112 (2013)
49. Xu, R. et al. Structural basis of preexisting immunity to the 2009 H1N1 pandemic influenza virus. Science 328, 357–360 (2010)