2,797
Views
0
CrossRef citations to date
0
Altmetric
Novel Vaccines

DNA and protein-generated chimeric molecules for delivery of influenza viral epitopes in mouse and humanized NSG transfer models

, , , & ORCID Icon
Article: 2292381 | Received 14 Oct 2023, Accepted 05 Dec 2023, Published online: 09 Jan 2024

References

  • Quiñones-Parra S, Clemens E, Wang Z, Croom H, Kedzierski L, McVernon J, Vijaykrishna D, Kedzierska K. A role of influenza virus exposure history in determining pandemic susceptibility and CD8+ T cell responses. J Virol. 2016;90(15):6936–12. doi:10.1128/JVI.00349-16.
  • Zimmer S, Burke D. Historical perspective — Emergence of influenza A (H1N1) viruses. N Engl J Med. 2009;361(3):279–285. doi:10.1056/NEJMra0904322.
  • Hause BM, Collin EA, Liu R, Huang B, Sheng Z, Lu W, Wang D, Nelson EA, Li F. Characterization of a novel influenza virus in cattle and swine: proposal for a new genus in the Orthomyxoviridae family. MBio. 2014;5(2):e00031–e14. doi:10.1128/mBio.00031-14.
  • Ruiz M, Puig A, Bassols M, Fraile L, Armengol R. Influenza D virus: a review and update of its role in bovine respiratory syndrome. Viruses. 2022;14(12):2717. doi:10.3390/v14122717.
  • Krammer F, Smith G, Fouchier R, Peiris M, Kedzierska K, Doherty PC, Palese P, Shaw ML, Treanor J, Webster RG, et al. Influenza. Nat Rev Dis Primers. 2018;4(1): Article number: 3. doi:10.1038/s41572-018-0002-y.
  • Mishra AC, Chadha MS, Choudhary ML, Potdar VA. Pandemic influenza (H1N1) 2009 is associated with severe disease in India. PLoS ONE. 2010;5:e10540. doi:10.1371/journal.pone.0010540.
  • Guthmiller J, Wilson P. Harnessing immune history to combat influenza viruses. Curr Opin Immunol. 2018;53:187–95. doi:10.1016/j.coi.2018.05.010.
  • Wilson JR, Guo Z, Reber A, Kamal RP, Music N, Gansebom S, Bai Y, Levine M, Carney P, Tzeng W-P, et al. An influenza a virus (H7N9) anti-neuraminidase monoclonal antibody with prophylactic and therapeutic activity in vivo. Antivir Res. 2016;135:48–55. doi:10.1016/j.antiviral.2016.10.001.
  • Sakai T, Nishimura SI, Naito T, Saito M. Influenza A virus hemagglutinin and neuraminidase act as novel motile machinery. Sci Rep. 2017;7(1):45043. doi:10.1038/srep45043.
  • Pizzorno A, Padey B, Terrier O, Rosa-Calatrava M. Drug repurposing approaches for the treatment of influenza viral infection: reviving old drugs to fight against a long-lived enemy. Front Immunol. 2019. doi:10.3389/fimmu.2019.00531.
  • Tutykhina I, Esmagambetov I, Bagaev A, Pichugin A, Lysenko A, Shcherbinin D, Sedova E, Logunov D, Shmarov M, Ataullakhanov R, et al. Vaccination potential of B and T epitope-enriched NP and M2 against influenza a viruses from different clades and hosts. PLoS ONE. 2018;13(1):e0191574. doi:10.1371/journal.pone.0191574.
  • Weidenbacher P, Kim P. Protect, modify, deprotect (PMD): a strategy for creating vaccines to elicit antibodies targeting a specific epitope. Proc Natl Acad Sci. 2019;116(20):9947–9952. doi:10.1073/pnas.1822062116.
  • Guo C, Zhang H, Xie X, Liu Y, Sun L, Li H, Yu P, Hu H, Sun J, Li Y, et al. H1N1 influenza virus epitopes classified by monoclonal antibodies. Exp Ther Med. 2018;16:2001–7. doi:10.3892/etm.2018.6429.
  • Gamblin SJ, Skehel JJ. Influenza hemagglutinin and neuraminidase membrane glycoproteins. J Biol Chem. 2010;285(37):28403–9. doi:10.1074/jbc.R110.129809.
  • Hamilton BS, Whittaker GR, Daniel S. Influenza virus-mediated membrane fusion: determinants of hemagglutinin fusogenic activity and experimental approaches for assessing virus fusion. Viruses. 2012;4(7):1144–68. doi:10.3390/v4071144.
  • Chambers BS, Parkhouse K, Ross TM, Alby K, Hensley SE. Identification of hemagglutinin residues responsible for H3N2 antigenic drift during the 2014–2015 influenza season. Cell Rep. 2015;12(1):1–6. doi:10.1016/j.celrep.2015.06.005.
  • Mallajosyula VV, Citron M, Ferrara F, NJ T, Liang X, JA F, Varadarajan R. Hemagglutinin sequence conservation guided stem immunogen design from influenza a H3 subtype. Front Immunol. 2015;6:329. doi:10.3389/fimmu.2015.00329.
  • Krammer F, Palese P. Advances in the development of influenza virus vaccines. Nat Rev Drug Discov. 2015;14(3):167–82. doi:10.1038/nrd4529.
  • Nagy Z, Rajnavolgyi E, Hollosi M, Tóth GK, Váradi G, Penke B, Tóth I, Horváth A, Gergely J, Kurucz I, et al. The intersubunit region of the influenza virus haemagglutinin is recognized by antibodies during infection. Scand J Immunol. 1994;40:281–91. doi:10.1111/j.1365-3083.1994.tb03464.x.
  • Rajnavolgyi E, Horvath A, Gogolak P, Tóth GK, Fazekas G, Fridkin M, Pecht I. Characterizing immunodominant and protective influenza hemagglutinin epitopes by functional activity and relative binding to major histocompatibility complex class II sites. Eur J Immunol. 1997;27:3105–14. doi:10.1002/eji.1830271205.
  • Ivanovska N, Tchorbanov A, Prechl J, Maximova V, Voynova E, Vassilev TL. Immunization with a DNA chimeric molecule encoding a hemagglutinin peptide and a scFv CD21-specific antibody fragment induces long-lasting IgM and CTL responses to influenza virus. Vaccine. 2006;24:1830–1837. doi:10.1016/j.vaccine.2005.10.029.
  • Prechl J, Tchorbanov A, Horvath A, Baiu DC, Hazenbos W, Rajnavölgyi É, Kurucz I, Capel PJA, Erdei A. Targeting of influenza epitopes to murine CR1/CR2 using single-chain antibodies. Immunopharmacol. 1999;42:159–65. doi:10.1016/S0162-3109(99)00025-9.
  • Gesheva V, Idakieva K, Kerekov N, Nikolova K, Mihaylova N, Doumanova L, Tchorbanov A. Marine gastropod hemocyanins as adjuvants of non-conjugated bacterial and viral proteins. Fish And Shellfish Immunol. 2011;30(1):135–142. doi:10.1016/j.fsi.2010.09.018.
  • Donnelly JJ, Wahren B, Liu MA. DNA vaccines: progress and challenges. J Immunol. 2005;175(2):633–9. doi:10.4049/jimmunol.175.2.633.
  • Porter KR, Raviprakash K. DNA vaccine delivery and improved immunogenicity. Curr Issues Mol Biol. 2017;22:129–38. doi:10.21775/cimb.022.129.
  • Li L, Petrovsky N. Molecular mechanisms for enhanced DNA vaccine immunogenicity. Expert Rev Vaccines. 2016;15(3):313–29. doi:10.1586/14760584.2016.1124762.
  • Song L, Xiong D, Kang X, Yang Y, Wang J, Guo Y, Xu H, Chen S, Peng D, Pan Z, et al. An avian influenza a (H7N9) virus vaccine candidate based on the fusion protein of hemagglutinin globular head and salmonella typhimurium flagellin. BMC Biotechnol. 2015;15(1):79. doi:10.1186/s12896-015-0195-z.
  • Wong TM, Ross TM. Use of computational and recombinant technologies for developing novel influenza vaccines. Expert Rev Vaccines. 2016;15(1):41–51. doi:10.1586/14760584.2016.1113877.
  • Berlanda Scorza F, Tsvetnitsky V, Donnelly JJ. Universal influenza vaccines: shifting to better vaccines. Vaccine. 2016;34(26):2926–33. doi:10.1016/j.vaccine.2016.03.085.
  • Carter DM, Darby CA, Lefoley BC, Crevar CJ, Alefantis T, Oomen R, Anderson SF, Strugnell T, Cortés-Garcia G, Vogel TU, et al. Design and characterization of a computationally optimized broadly reactive hemagglutinin vaccine for H1N1 influenza viruses. J Virol. 2016;90(9):4720–34. doi:10.1128/JVI.03152-15.
  • Rice J, Ottensmeier C, Stevenson F. DNA vaccines: precision tools for activating effective immunity against cancer. Nat Rev Cancer. 2008;8(2):108–20. doi:10.1038/nrc2326.
  • Grodeland G, Fredriksen AB, GÅ L, Vikse E, Fugger L, Bogen B. Antigen targeting to human HLA class II molecules increases efficacy of DNA vaccination. J Immunol. 2016;197:3575–85. doi:10.4049/jimmunol.1600893.
  • Barría MI, Garrido JL, Stein C, Scher E, Ge Y, Engel SM, Kraus TA, Banach D, Moran TM. Localized mucosal response to intranasal live attenuated influenza vaccine in adults. J Infect Dis. 2013;207:115–24. doi:10.1093/infdis/jis641.
  • Whittle JR, Wheatley AK, Wu L, Lingwood D, Kanekiyo M, Ma SS, Narpala SR, Yassine HM, Frank GM, Yewdell JW, et al. Flow cytometry reveals that H5N1 vaccination elicits cross-reactive stem-directed antibodies from multiple ig heavy-chain lineages. J Virol. 2014;88(8):4047–57. doi:10.1128/JVI.03422-13.
  • Yan J, Morrow MP, Chu JS, Racine T, Reed CC, Khan AS, Broderick KE, Kim JJ, Kobinger GP, Sardesai NY, et al. Broad cross- protective anti-hemagglutination responses elicited by influenza microconsensus DNA vaccine. Vaccine. 2018;36(22):3079–89. doi:10.1016/j.vaccine.2017.09.086.
  • DeZure AD, Coates EE, Hu Z, Yamshchikov GV, Zephir KL, Enama ME, Plummer SH, Gordon IJ, Kaltovich F, Andrews S, et al. An avian influenza H7 DNA priming vaccine is safe and immunogenic in a randomized phase I clinical trial. NPJ Vaccines. 2017;2:15. doi:10.1038/s41541-017-0016-6.
  • Stachyra A, Pietrzak M, Macioła A, Protasiuk A, Olszewska M, Śmietanka K, Minta Z, Góra-Sochacka A, Kopera E, Sirko A, et al. A prime/boost vaccination with HA DNA and pichia-produced HA protein elicits a strong humoral response in chickens against H5N1. Virus Res. 2017;232:41–7. doi:10.1016/j.virusres.2017.01.025.
  • Shibabaw T, Molla MD, Teferi B, Ayelign B. Role of IFN and complements system: innate immunity in SARS-CoV-2. J Inflamm Res. 2020;13:507–18. doi:10.2147/JIR.S267280.
  • Kranich J, Krautler N-J. How follicular dendritic cells shape the B-Cell antigenome. Front Immunol. 2016;7:225. doi:10.3389/fimmu.2016.00225.
  • Bennett K, Rooijakkers S, Gorham R. Let’s tie the knot: marriage of complement and adaptive immunity in pathogen evasion, for better or worse. Front Microbiol. 2017;8:89. doi:10.3389/fmicb.2017.00089.
  • García-García E, Rosales C. Fc receptor signaling in leukocytes: role in host defense and immune regulation. Curr Immunol Rev. 2009;5(3):227–42. doi:10.2174/157339509788921229.
  • Guilliams M, Bruhns P, Saeys Y, Hammad H, Lambrecht BN. The function of Fcγ receptors in dendritic cells and macrophages. Nat Rev Immunol. 2014;14:94–108. doi:10.1038/nri3582.
  • Zhong T-Y, Arancibia S, Born R, Tampe R, Villar J, Campo M, Manubens A, Becker MI. Hemocyanins stimulate innate immunity by inducing different temporal patterns of proinflammatory cytokine expression in macrophages. J Immunol. 2016;196(11):4650–4662. doi:10.4049/jimmunol.1501156.
  • Jiménez J, Salazar M, Arancibia S, Villar J, Salazar F, Brown G, Lavelle EC, Martínez-Pomares L, Ortiz-Quintero J, Lavandero S, et al. TLR4, but neither dectin-1 nor dectin-2, participates in the Mollusk hemocyanin-induced proinflammatory effects in antigen-presenting cells from mammals. Front Immunol. 2019;10:1136. doi:10.3389/fimmu.2019.01136.
  • Grødeland G, Fossum E, Bogen B. Polarizing T and B cell responses by APC-Targeted subunit vaccines. Front Immunol. 2015;6:367. doi:10.3389/fimmu.2015.00367.
  • Gesheva V, Chausheva S, Stefanova N, Mihaylova N, Doumanova L, Idakieva K, Tchorbanov A. Helix pomatia hemocyanin - a novel bio-adjuvant for viral and bacterial antigens. Int Immunopharmacol. 2015;26(1):162–168. doi:10.1016/j.intimp.2015.03.011.
  • Gong YM, Wei XF, Zheng YY, Li Y, Yu Q, Li PF, Zhu B, Schultz-Cherry S. Combining phage display technology with in silico-designed epitope vaccine to elicit robust antibody responses against emerging pathogen tilapia lake virus. J Virol. 2023;97(4):e0005023. doi:10.1128/jvi.00050-23.
  • Ahmad Z, Yeap S, Ali A, Ho W-Y, Noorjahan B, Hamid M. scFv antibody: principles and clinical application. Clin Dev Immunol. 2012;2012:1–15. doi:10.1155/2012/980250.
  • Satheeshkumar PK. Expression of single chain variable fragment (scFv) molecules in plants: a comprehensive update. Mol Biotechnol. 2020;62(3):151–67. doi:10.1007/s12033-020-00241-3.
  • Sarker A, Rathore AS, Gupta RD. Evaluation of scFv protein recovery from E. coli by in vitro refolding and mild solubilization process. Microb Cell Fact. 2019;18:5. doi:10.1186/s12934-019-1053-9.
  • Ahmad ZA, Yeap SK, Ali AM, Ho WY, Alitheen NB, Hamid M. scFv antibody: principles and clinical application. Clin Dev Immunol. 2012;2012:980250. doi:10.1155/2012/980250.
  • Yusakul G, Sakamoto S, Pongkitwitoon B, Tanaka H, Morimoto S. Effect of linker length between variable domains of single chain variable fragment antibody against daidzin on its reactivity. Biosci Biotechnol Biochem. 2016;80(7):1306–12. doi:10.1080/09168451.2016.1156482.
  • Kobayashi N, Ohtoyo M, Wada E, Kato Y, Mano N, Goto J. Generation of a single-chain Fv fragment for the monitoring of deoxycholic acid residues anchored on endogenous proteins. Steroids. 2005;70(4):285–94. doi:10.1016/j.steroids.2004.11.012.
  • Dai K, Zhu H, Ruan C. Generation and characterization of recombinant single chain Fv antibody that recognizes platelet glycoprotein Ibα. Thromb Res. 2003;109(2–3):137–44. doi:10.1016/S0049-3848(03)00152-X.
  • Sakai K, Shimizu Y, Chiba T, Matsumoto-Takasaki A, Kusada Y, Zhang W, Nakata M, Kojima N, Toma K, Takayanagi A, et al. Isolation and characterization of phage-displayed single chain antibodies recognizing nonreducing terminal mannose residues. 1. A new strategy for generation of anti-carbohydrate antibodies. Biochemistry. 2007;46(1):253–62. doi:10.1021/bi061875e.
  • Liang GQ, Liu J, Zhou XX, Lin ZX, Chen T, Chen G, Wei H. Anti-CXCR4 single-Chain variable fragment antibodies have anti-tumor activity. Front Oncol. 2020;10:571194. doi:10.3389/fonc.2020.571194. PMID: 33392074; PMCID: PMC7775505.
  • Rajput R, Sharma G, Rawat V, Gautam A, Kumar B, Pattnaik B, Pradhan HK, Khanna M. Diagnostic potential of recombinant {scFv} antibodies generated against hemagglutinin protein of influenza A virus. Front Immunol. 2015;6. doi:10.3389/fimmu.2015.00440.
  • Herati RS, Wherry EJ. What is the predictive value of animal models for vaccine efficacy in humans? Consideration of strategies to improve the value of animal models. Cold Spring Harb Perspect Biol. 2018;10(4):a031583. doi:10.1101/cshperspect.a031583.
  • Krishnakumar V, Durairajan SSK, Alagarasu K, Li M, Dash AP. Recent updates on mouse models for human immunodeficiency, influenza, and dengue viral infections. Viruses. 2019;11(3):252. doi:10.3390/v11030252.
  • Lai F, Chen Q. Humanized mouse models for the study of infection and pathogenesis of human viruses. Viruses. 2018;10(11):643. doi:10.3390/v10110643. PMID: 30453598; PMCID: PMC6266013.
  • Theocharides AP, Rongvaux A, Fritsch K, Flavell RA, Manz MG. Humanized hemato-lymphoid system mice. Haematologica. 2016;101(1):5–19. doi:10.3324/haematol.2014.115212.
  • Ishikawa F, Yasukawa M, Lyons B, Yoshida S, Miyamoto T, Yoshimoto G, Watanabe T, Akashi K, Shultz LD, Harada M. Development of functional human blood and immune systems in NOD/SCID/IL2 receptor γ chainnull mice. Blood. 2005;106(5):1565–73. doi:10.1182/blood-2005-02-0516.
  • Brehm MA, Bortell R, Verma M, Shultz LD, Greiner DL. Chapter 11 - Humanized mice in translational immunology. In: Tan SL, editors. Translational immunology. Academic Press; 2016. p. 285–326. doi:10.1016/B978-0-12-801577-3.00012-5.
  • Shultz LD, Brehm MA, Garcia-Martinez JV, Greiner DL. Humanized mice for immune system investigation: progress, promise and challenges. Nat Rev Immunol. 2012;12(11):786–98. doi:10.1038/nri3311.
  • Walsh N, Kenney L, Jangalwe S, Aryee KE, Greiner DL, Brehm MA, Shultz LD. Humanized mouse models of clinical disease. Annu Rev Pathol. 2017;12(1):187–215. doi:10.1146/annurev-pathol-052016-100332.
  • Sasaki E, Momose H, Hiradate Y, Furuhata K, Mizukami T, Hamaguchi I. Development of a preclinical humanized mouse model to evaluate acute toxicity of an influenza vaccine. Oncotarget. 2018;9(40):25751. doi:10.18632/oncotarget.25399.
  • Dadonaite B, Gilbertson B, Knight ML, Trifkovic S, Rockman S, Laederach A, Brown LE, Fodor E, Bauer DLV. The structure of the influenza a virus genome. Nature Microbiology. 2019;4(11):1781–1789. doi:10.1038/s41564-019-0513-7.
  • Kerekov N, Ivanova I, Mihaylova N, Nikolova M, Prechl J, Tchorbanov A. Built-in adjuvanticity of genetically and protein engineered chimeric molecules for targeting of influenza a peptide epitopes. Immunol Research. 2014;60(1):23–34. doi:10.1007/s12026-014-8489-0.
  • Kinoshita T, Takeda J, Hong K, Kozono H, Sakai H, Inoue K. Monoclonal antibodies to mouse complement receptor type 1 (CR1): their use in a distribution study showing that mouse erythrocytes and platelets are CR1-negative. J Immunol. 1988;140:3066. doi:10.4049/jimmunol.140.9.3066.
  • Tchorbanov A, Voynova E, Mihaylova N, Todorov T, Nikolova M, Yomtova VM, Chiang B-L, Vassilev T. Selective silencing of DNA-specific B lymphocytes delays lupus activity in MRL/lpr mice. Eur J Immunol. 2007;37:3587–3596. doi:10.1002/eji.200737143.
  • Gesheva V, Chausheva S, Stefanova N, Mihaylova N, Doumanova L, Idakieva K, Tchorbanov A. Helix pomatia hemocyanin - a novel bio-adjuvant for viral and bacterial antigens. Int Immunopharmacol. 2015;1:162–8. doi:10.1016/j.intimp.2015.03.011. Epub 2015 Mar 20. PMID: 25799956.
  • Ivanova I, Mihaylova N, Manoylov I, Makatsori D, Lolov S, Nikolova M, Mamalaki A, Prechl J, Tchorbanov A. Targeting of Influenza viral epitopes to antigen presenting cells by Genetically Engineered Chimeric Molecules in Humanized NSG transfer model. Hum Gene Ther. 2018;29:(9):1056–1070. doi:10.1089/hum.2018.100.
  • Rimmelzwaan GF, McElhaney JE. Correlates of protection: novel generations of influenza vaccines. Vaccine. 2008;26:D41–4. doi:10.1016/j.vaccine200807043.
  • Xenopoulos A, Pattnaik P. Production and purification of plasmid DNA vaccines: is there scope for further innovation? Expert Rev Vaccines. 2014;13(12):1537–51. doi:10.1586/14760584.2014.968556.
  • Gerdts V, Wilson HL, Meurens F, Van Drunen Littel-Van Den Hurk S, Wilson D, Walker S, Wheler C, Townsend H, Potter AA. Large animal models for vaccine development and testing. ILAR J. 2015;56:53. doi:10.1093/ilar/ilv009.
  • Klenerman P, Zinkernagel R. Original antigenic sin impairs cytotoxic T lymphocyte responses to viruses bearing variant epitopes. Nature. 1998;394(6692):482–5. doi:10.1038/28860.
  • Bot A, Isobe H, Bona C. Immunodeficient mouse models in the characterization of the protective immunity to influenza virus. Folia Microbiol. 1998;43(5):477–8. doi:10.1007/BF02820795.
  • Brumeanu TD, Casares S, Harris PE, Dehazya P, Wolf I, von Boehmer H, Bona CA. Immunopotency of a viral peptide assembled on the carbohydrate moieties of self immunoglobulins. Nat Biotechnol. 1996;14(6):722–5. doi:10.1038/nbt0696-722. PMID: 9630978.
  • Zaghouani H, Steinman R, Nonacs R, Shah H, Gerhard W, Bona C. Presentation of a viral T cell epitope expressed in the CDR3 region of a self immunoglobulin molecule. Sci. 1993;259(5092):224–7. doi:10.1126/science.7678469. PMID: 7678469.
  • Casares S, Brumeanu TD, Bot A, Bona CA. Protective immunity elicited by vaccination with DNA encoding for a B cell and a T cell epitope of the A/PR/8/34 influenza virus. Viral Immunol. 1997;10(3):129–36. PMID: 9344335. doi: 10.1089/vim.1997.10.129.
  • Bot A, Antohi S, Bot S, Garcia-Sastre A, Bona C. Induction of humoral and cellular immunity against influenza virus by immunization of newborn mice with a plasmid bearing a hemagglutinin gene. Int Immunol. 1997;9(11):1641–50. doi: 10.1093/intimm/9.11.1641. PMID: 9418125.
  • Brumeanu TD, Bot A, Bona CA, Dehazya P, Wolf I, Zaghouani H. Engineering of doubly antigenized immunoglobulins expressing T and B viral epitopes. Immunotechnology. 1996;2(2):85–95. doi:10.1016/1380-2933(96)85196-7. PMID: 9373317.
  • Li SQ, Schulman JL, Moran T, Bona C, Palese P. Influenza a virus transfectants with chimeric hemagglutinins containing epitopes from different subtypes. J Virol. 1992;66(1):399–404. doi:10.1128/JVI.66.1.399-404.1992. PMID: 1370088; PMCID: PMC238299.
  • Bot A, Reichlin A, Isobe H, Bot S, Schulman J, Yokoyama WM, Bona CA. Cellular mechanisms involved in protection and recovery from influenza virus infection in immunodeficient mice. J Virol. 1996;70(8):5668–72. doi:10.1128/JVI.70.8.5668-5672.1996. PMID: 8764086; PMCID: PMC190532.
  • Kirchenbaum GA, Ross TM. Eliciting broadly protective antibody responses against influenza. Curr Opin Immunol. 2014;28:71–6. doi:10.1016/j.coi.2014.02.005.
  • Nussing S, Sant, S., Koutsakos, M., Subbarao, K., Nguyen, T.H.O., Kedzierska, K. Innate and adaptive T cells in influenza disease. Front Med. 2018;12(1):34–47. doi:10.1007/s11684-017-0606-8.
  • Liao HY, Wang SC, Ko YA, Lin KI, Ma C, Cheng TR, Wong CH. Chimeric hemagglutinin vaccine elicits broadly protective CD4 and CD8 T cell responses against multiple influenza strains and subtypes. Proc Natl Acad Sci U S A. 2020 Jul 28;117(30):17757–17763. doi:10.1073/pnas.2004783117. Epub 2020. PMID: 32669430; PMCID: PMC7395492.
  • Puente-Massaguer E, Vasilev K, Beyer A, Loganathan M, Francis B, Scherm MJ, Arunkumar GA, González-Domínguez I, Zhu X, Wilson IA, et al. Chimeric hemagglutinin split vaccines elicit broadly cross-reactive antibodies and protection against group 2 influenza viruses in mice. Sci Adv. 2023;9(37):eadi4753. doi:10.1126/sciadv.adi4753. Epub 2023 Sep 13. PMID: 37703367; PMCID: PMC10499326.
  • Nachbagauer R, Feser J, Naficy A, Bernstein DI, Guptill J, Walter EB, Berlanda-Scorza F, Stadlbauer D, Wilson PC, Aydillo T, et al. A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial. Nat Med. 2021;27(1):106–14. doi:10.1038/s41591-020-1118-7.
  • Puente-Massaguer E, Beyer A, Loganathan M, Sapse I, Carreño JM, Bajic G, Sun W, Palese P, Krammer F. Bioprocess development for universal influenza vaccines based on inactivated split chimeric and mosaic hemagglutinin viruses. Front Bioeng Biotechnol. 2023;11:1097349. doi:10.3389/fbioe.2023.1097349. PMID: 37342504; PMCID: PMC10277804.
  • Carroll MC. The complement system in B cell regulation. Mol Immunol. 2004;41(2–3):141–6. doi:10.1016/j.molimm.2004.03.017.
  • Molina H, Holers VM, Li B, Fang Y-F, Mariathasan S, Goellner J, Strauss-Schoenberger J, Karr RW, Chaplin DD. Markedly impaired humoral immune response in mice deficient in complement receptors 1 and 2. Proc Natl Acad Sci U S A. 1996;93:3357. doi:10.1073/pnas.93.8.3357.
  • Saha R, Killian S, Robert D. DNA vaccines: a mini review. Recent patents on DNA & gene sequences. 2011;5(2):92–96. doi:10.2174/187221511796392114.
  • Carter DM, Darby CA, Johnson SK, Carlock MA, Kirchenbaum GA, DiNapoli J, Vogel TU, Delagrave S, DiNapoli J, Kleanthous H, et al. Elicitation of protective antibodies against a broad panel of H1N1 viruses in ferrets pre-immune to historical H1N1 influenza viruses. J Virol. 2017;91. doi:10.1128/JVI.01283-17.
  • Crevar CJ, Carter DM, Lee KY, Ross TM. Cocktail of H5N1 COBRA HA vaccines elicit protective antibodies against H5N1 viruses from multiple clades. Hum Vaccin Immunother. 2015;11(3):572–83. doi:10.1080/21645515.2015.1012013.