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Research Article

Virus-like particles coexpressing the PreF and Gt antigens of respiratory syncytial virus confer protection in mice

    Ki-Back Chu

    Medical Research Center for Bioreaction to Reactive Oxygen Species & Biomedical Science Institute, School of Medicine, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea

    ,
    Su-Hwa Lee

    Department of Medical Zoology, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea

    ,
    Min-Ju Kim

    Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea

    ,
    Ah-Ra Kim

    Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea

    ,
    Eun-Kyung Moon

    Department of Medical Zoology, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea

    &
    Fu-Shi Quan

    *Author for correspondence: Tel.: +822 961 2302;

    E-mail Address: fsquan@khu.ac.kr

    Medical Research Center for Bioreaction to Reactive Oxygen Species & Biomedical Science Institute, School of Medicine, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea

    Department of Medical Zoology, School of Medicine, Kyung Hee University, Seoul, 02447, Republic of Korea

    Published Online:https://doi.org/10.2217/nnm-2022-0082

    Aims: The purpose of this study was to assess the protective efficacy of virus-like particles (VLPs) co-expressing the pre-fusogenic (PreF) and G protein with tandem repeats (Gt) antigens of respiratory syncytial virus (RSV) in mice. Materials & methods: VLP constructs expressing PreF, Gt or both were used to immunize mice, and the protective efficacies were evaluated using antibody responses, neutralizing antibody titers, T-cell responses, histopathological assessment and plaque assay. Results: PreF+Gt VLP immunization elicited strong RSV-specific antibody responses and pulmonary T-cell responses that contributed to lessening virus titer and inflammation. Conclusion: Our findings suggest that coexpressing PreF and Gt antigens elicits better protection than either one alone. This combinatorial approach could assist in future RSV vaccine development.

    References

    • 1. Shi T, Mcallister DA, O’Brien KL et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet 390(10098), 946–958 (2017).
    • 2. Kushnir N, Streatfield SJ, Yusibov V. Virus-like particles as a highly efficient vaccine platform: diversity of targets and production systems and advances in clinical development. Vaccine 31(1), 58–83 (2012).
    • 3. Mazur NI, Higgins D, Nunes MC et al. The respiratory syncytial virus vaccine landscape: lessons from the graveyard and promising candidates. Lancet Infect. Dis. 18(10), e295–e311 (2018).
    • 4. Besteman SB, Bont LJ. Fail-fast in respiratory syncytial virus vaccine development. Am. J. Respir. Crit. Care Med. 200(4), 410–412 (2019).
    • 5. Blunck BN, Rezende W, Piedra PA. Profile of respiratory syncytial virus prefusogenic fusion protein nanoparticle vaccine. Expert Rev. Vaccines 20(4), 351–364 (2021).
    • 6. Mclellan JS, Chen M, Joyce MG et al. Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus. Science 342(6158), 592–598 (2013).
    • 7. Killikelly AM, Kanekiyo M, Graham BS. Pre-fusion F is absent on the surface of formalin-inactivated respiratory syncytial virus. Sci. Rep. 6, 34108 (2016).
    • 8. Saeland E, van der Fits L, Bolder R et al. Immunogenicity and protective efficacy of adenoviral and subunit RSV vaccines based on stabilized prefusion F protein in pre-clinical models. Vaccine 40(6), 934–944 (2021).
    • 9. Sadoff J, De Paepe E, Devincenzo J et al. Prevention of respiratory syncytial virus infection in healthy adults by a single immunization of Ad26.RSV.preF in a human challenge study. J. Infect. Dis. 226(3), 396–406 (2022).
    • 10. Sadoff J, De Paepe E, Haazen W et al. Safety and immunogenicity of the Ad26.RSV.preF investigational vaccine coadministered with an influenza vaccine in older adults. J. Infect. Dis. 223(4), 699–708 (2021).
    • 11. Patel N, Massare MJ, Tian JH et al. Respiratory syncytial virus prefusogenic fusion (F) protein nanoparticle vaccine: structure, antigenic profile, immunogenicity, and protection. Vaccine 37(41), 6112–6124 (2019).
    • 12. Welliver RC, Papin JF, Preno A et al. Maternal immunization with RSV fusion glycoprotein vaccine and substantial protection of neonatal baboons against respiratory syncytial virus pulmonary challenge. Vaccine 38(5), 1258–1270 (2020).
    • 13. Kwon YM, Lee Y, Kim KH et al. Antigenicity and immunogenicity of unique prefusion-mimic F proteins presented on enveloped virus-like particles. Vaccine 37(44), 6656–6664 (2019).
    • 14. Swanson KA, Rainho-Tomko JN, Williams ZP et al. A respiratory syncytial virus (RSV) F protein nanoparticle vaccine focuses antibody responses to a conserved neutralization domain. Sci. Immunol. 5(47), eaba6466 (2020).
    • 15. Patel N, Tian JH, Flores R et al. Flexible RSV prefusogenic fusion glycoprotein exposes multiple neutralizing epitopes that may collectively contribute to protective immunity. Vaccines (Basel.) 8(4), 607 (2020).
    • 16. Young MD, Gooch WM 3rd, Zuckerman AJ, Du W, Dickson B, Maddrey WC. Comparison of a triple antigen and a single antigen recombinant vaccine for adult hepatitis B vaccination. J. Med. Virol. 64(3), 290–298 (2001).
    • 17. Kim AR, Lee DH, Lee SH, Rubino I, Choi HJ, Quan FS. Protection induced by virus-like particle vaccine containing tandem repeat gene of respiratory syncytial virus G protein. PLOS ONE 13(1), e0191277 (2018).
    • 18. Quan FS, Kim Y, Lee S et al. Viruslike particle vaccine induces protection against respiratory syncytial virus infection in mice. J. Infect. Dis. 204(7), 987–995 (2011).
    • 19. Kim KS, Kim AR, Piao Y, Lee JH, Quan FS. A rapid, simple, and accurate plaque assay for human respiratory syncytial virus (HRSV). J. Immunol. Methods 446, 15–20 (2017).
    • 20. Kang HJ, Chu KB, Lee DH et al. Influenza M2 virus-like particle vaccination enhances protection in combination with avian influenza HA VLPs. PLOS ONE 14(6), e0216871 (2019).
    • 21. Lee S, Quan FS, Kwon Y et al. Additive protection induced by mixed virus-like particles presenting respiratory syncytial virus fusion or attachment glycoproteins. Antiviral Res. 111, 129–135 (2014).
    • 22. Hwang HS, Lee YT, Kim KH et al. Combined virus-like particle and fusion protein-encoding DNA vaccination of cotton rats induces protection against respiratory syncytial virus without causing vaccine-enhanced disease. Virology 494, 215–224 (2016).
    • 23. Cullen LM, Schmidt MR, Morrison TG. The importance of RSV F protein conformation in VLPs in stimulation of neutralizing antibody titers in mice previously infected with RSV. Hum. Vaccin. Immunother. 13(12), 2814–2823 (2017).
    • 24. Gómez-Puertas P, Albo C, Pérez-Pastrana E, Vivo A, Portela A. Influenza virus matrix protein is the major driving force in virus budding. J. Virol. 74(24), 11538–11547 (2000).
    • 25. Kumar B, Hawkins GM, Kicmal T, Qing E, Timm E, Gallagher T. Assembly and entry of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2): evaluation using virus-like particles. Cells 10(4), 853 (2021).
    • 26. Fisher RG, Crowe JE Jr, Johnson TR, Tang YW, Graham BS. Passive IgA monoclonal antibody is no more effective than IgG at protecting mice from mucosal challenge with respiratory syncytial virus. J. Infect. Dis. 180(4), 1324–1327 (1999).
    • 27. Tree JA, Bembridge G, Hou S et al. An assessment of different DNA delivery systems for protection against respiratory syncytial virus infection in the murine model: gene-gun delivery induces IgG in the lung. Vaccine 22(19), 2438–2443 (2004).
    • 28. Liang B, Hyland L, Hou S. Nasal-associated lymphoid tissue is a site of long-term virus-specific antibody production following respiratory virus infection of mice. J. Virol. 75(11), 5416–5420 (2001).
    • 29. Debertin AS, Tschernig T, Tönjes H, Kleemann WJ, Tröger HD, Pabst R. Nasal-associated lymphoid tissue (NALT): frequency and localization in young children. Clin. Exp. Immunol. 134(3), 503–507 (2003).
    • 30. Polack FP, Teng MN, Collins PL et al. A role for immune complexes in enhanced respiratory syncytial virus disease. J. Exp. Med. 196(6), 859–865 (2002).
    • 31. Delgado MF, Coviello S, Monsalvo AC et al. Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease. Nat. Med. 15(1), 34–41 (2009).
    • 32. Krause A, Xu Y, Ross S, Wu W, Joh J, Worgall S. Absence of vaccine-enhanced RSV disease and changes in pulmonary dendritic cells with adenovirus-based RSV vaccine. Virol. J. 8, 375 (2011).
    • 33. Cannon MJ, Stott EJ, Taylor G, Askonas BA. Clearance of persistent respiratory syncytial virus infections in immunodeficient mice following transfer of primed T cells. Immunology 62(1), 133–138 (1987).
    • 34. Jozwik A, Habibi MS, Paras A et al. RSV-specific airway resident memory CD8+ T cells and differential disease severity after experimental human infection. Nat. Commun. 6, 10224 (2015).
    • 35. Schmidt ME, Varga SM. The CD8 T cell response to respiratory virus infections. Front. Immunol. 9, 678 (2018).
    • 36. Schmidt ME, Varga SM. Cytokines and CD8 T cell immunity during respiratory syncytial virus infection. Cytokine 133, 154481 (2020).
    • 37. Ostler T, Davidson W, Ehl S. Virus clearance and immunopathology by CD8(+) T cells during infection with respiratory syncytial virus are mediated by IFN-gamma. Eur. J. Immunol. 32(8), 2117–2123 (2002).
    • 38. Hwang HS, Kim KH, Lee Y et al. Virus-like particle vaccines containing F or F and G proteins cofer protection against respiratory syncytial virus without pulmonary inflammation in cotton rats. Hum. Vaccin. Immunother.. 13(5), 1031–1039 (2017).
    • 39. Fuentes S, Coyle EM, Golding H, Khurana S. Nonglycosylated G-protein vaccine protects against homologous and heterologous respiratory syncytial virus (RSV) challenge, while glycosylated G enhances RSV lung pathology and cytokine levels. J. Virol. 89(16), 8193–8205 (2015).
    • 40. Tomiya N, Betenbaugh MJ, Lee YC. Humanization of lepidopteran insect-cell-produced glycoproteins. Acc. Chem. Res. 36(8), 613–620 (2003).
    • 41. Mcginnes Cullen L, Schmidt MR, Kenward SA, Woodland RT, Morrison TG. Murine immune responses to virus-like particle-associated pre- and postfusion forms of the respiratory syncytial virus F protein. J. Virol. 89(13), 6835–6847 (2015).
    • 42. Kim KH, Lee YT, Hwang HS et al. Virus-like particle vaccine containing the F protein of respiratory syncytial virus confers protection without pulmonary disease by modulating specific subsets of dendritic cells and effector T cells. J. Virol. 89(22), 11692–11705 (2015).
    • 43. Lenny BJ, Sonnberg S, Danner AF et al. Evaluation of multivalent H2 influenza pandemic vaccines in mice. Vaccine 35(10), 1455–1463 (2017).
    • 44. Lee YT, Ko EJ, Kim KH et al. Cellular immune correlates preventing disease against respiratory syncytial virus by vaccination with virus-like nanoparticles carrying fusion proteins. J. Biomed. Nanotechnol. 13(1), 84–98 (2017).
    • 45. Lee YT, Ko EJ, Hwang HS et al. Respiratory syncytial virus-like nanoparticle vaccination induces long-term protection without pulmonary disease by modulating cytokines and T-cells partially through alveolar macrophages. Int. J. Nanomed. 10, 4491–4505 (2015).
    • 46. Pease LF 3rd, Lipin DI, Tsai DH et al. Quantitative characterization of virus-like particles by asymmetrical flow field flow fractionation, electrospray differential mobility analysis, and transmission electron microscopy. Biotechnol. Bioeng. 102(3), 845–855 (2009).
    • 47. Nooraei S, Bahrulolum H, Hoseini ZS et al. Virus-like particles: preparation, immunogenicity and their roles as nanovaccines and drug nanocarriers. J. Nanobiotechnol. 19(1), 59 (2021).