3,078
Views
22
CrossRef citations to date
0
Altmetric
Review

The use of cell-mediated immunity for the evaluation of influenza vaccines: an upcoming necessity

, &
Pages 1021-1030 | Received 02 Oct 2018, Accepted 27 Dec 2018, Published online: 20 Feb 2019

References

  • [accessed 2018 Dec 01].http://www.who.int/news-room/fact-sheets/detail/influenza-(seasonal)
  • Wong KK, Jain S, Blanton L, Dhara R, Brammer L, Fry AM, Finelli L. Influenza-associated pediatric deaths in the United States, 2004-2012. Pediatrics. 2013;132(5):796–804. doi:10.1542/peds.2013-1493.
  • Heltzer ML, Coffin SE, Maurer K, Bagashev A, Zhang Z, Orange JS, Sullivan KE. Immune dysregulation in severe influenza. J Leukoc Biol. 2009;85(6):1036–43. doi:10.1189/jlb.1108710.
  • [accessed 2018 Dec 02] https://www.cdc.gov/flu/consumer/symptoms.htm
  • Bailey KL, Smith LM, Heires AJ, Katafiasz DM, Romberger DJ, LeVan TD. Aging leads to dysfunctional innate immune responses to TLR2 and TLR4 agonists. Aging Clin Exp Res. Nov 7 2018. doi: 10.1007/s40520-018-1064-0
  • Ventura MT, Casciaro M, Gangemi S, Buquicchio R. Immunosenescence in aging: between immune cells depletion and cytokines up-regulation. Clin Mol Allergy. 2017;15:21. doi:10.1186/s12948-017-0077-0.
  • Moro-Garcıa MA, Alonso-Arias R, Lopez-Larrea C. Molecular mechanisms involved in the aging of the T-cell immune response. Current Genomics. 2012;13(8):589–602. doi:10.2174/138920212803759749.
  • Zeman AM, Holmes TH, Stamatis S, Tu W, He XS, Bouvier N, Kemble G, Greenberg HB, Lewis DB, Arvin AM, et al. Humoral and cellular immune responses in children given annual immunization with trivalent inactivated influenza vaccine. Pediatr Infect Dis J. 2007;26:107–15. doi:10.1097/01.inf.0000253251.03785.9b.
  • Fiore AE, Bridges CB, Cox NJ. Seasonal influenza vaccines. Curr Top Microbiol Immunol. 2009;333:43–82. doi:10.1007/978-3-540-92165-3_3.
  • Plotkin SA. Correlates of protection induced by vaccination. Clin Vaccine Immunol. 2010;17(7):1055–65. doi:10.1128/CVI.00131-10.
  • Trombetta CM, Perini D, Mather S, Temperton N, Montomoli E. Overview of serological techniques for influenza vaccine evaluation: past, present and future. Vaccines. 2014;2:707‐734. doi:10.3390/vaccines2040707.
  • Henle W, Stokes J Jr, Shaw DR. Passive immunization of mice against human influenza virus by the intranasal route. J Immunol. 1941;40:201–12.
  • Gerhard W, Mozdzanowska K, Furchner M, Washko G, Maiese K. Role of the B-cell response in recovery of mice from primary influenza virus infection. Immunol Rev. 1997;159:95–103.
  • Zinkernagel RM. Maternal antibodies, childhood infections, and autoimmune diseases. N Engl J Med. 2001;345:1331–35. doi:10.1056/NEJMra012493.
  • Zaman K, Roy E, Arifeen SE, Rahman M, Raqib R, Wilson E, Omer SB, Shahid NS, Breiman RF, Steinhoff MC. Effectiveness of maternal influenza immunization in mothers and infants. N Engl J Med. 2008;359:1555–15564. doi:10.1056/NEJMoa0708630.
  • Ramos EL, Mitcham JL, Koller TD, Bonavia A, Usner DW, Balaratnam G, Fredlund P, Swiderek KM. Efficacy and safety of treatment with an anti-m2e monoclonal antibody in experimental human influenza. J Infect Dis. 2015;211:1038–44. doi:10.1093/infdis/jiu539.
  • Montomoli E, Torelli A, Manini I, Gianchecchi E. Immunogenicity and safety of the new inactivated quadrivalent influenza vaccine vaxigrip tetra: preliminary results in children ≥6 months and older adults. Vaccines (Basel). 2018:6. doi:10.3390/vaccines6010014.
  • Pavlova S, D’Alessio F, Houard S, Remarque EJ, Stockhofe N, Engelhardt OG. Workshop report: immunoassay standardisation for “universal” influenza vaccines. Influenza Other Respir Viruses. 2017;11:194–201. doi:10.1111/irv.12445.
  • Russell SM, McCahon D, Beare AS. A single radial haemolysis technique for the measurement of influenza antibody. J Gen Virol. 1975;27:1–10.6. doi:10.1099/0022-1317-27-1-1.
  • Schild GC, Pereira MS, Chakraverty P. Single-radial-hemolysis: a new method for the assay of antibody to influenza haemagglutinin. Applications for diagnosis and seroepidemiologic surveillance of influenza. Bull World Health Organ. 1975;52:43–50.
  • Salk JE. A simplified procedure for titrating hemagglutinating capacity of influenza virus and the corresponding antibody. J Immunol. 1944;49:87–98.
  • Trombetta CM, Perini D, Vitale L, Cox RJ, Stanzani V, Piccirella S, Montomoli E. Validation of single radial haemolysis assay: A reliable method to measure antibodies against influenza viruses. J Immunol Methods. 2015;422:95–101. doi:10.1016/j.jim.2015.04.009.
  • Trombetta CM, Montomoli E. Influenza immunology evaluation and correlates of protection: a focus on vaccines. Expert Rev Vaccines. 2016;15:967–76. doi:10.1586/14760584.2016.1164046.
  • Cox RJ. Correlates of protection to influenza virus, where do we go from here? Hum Vaccin Immunother. 2013;9:405–08.
  • Trombetta CM, Remarque EJ, Mortier D, Montomoli E. Comparison of hemagglutination inhibition, single radial hemolysis, virus neutralization assays, and ELISA to detect antibody levels against seasonal influenza viruses. Influenza Other Respir Viruses. 2018;12(6):675–86. doi:10.1111/irv.12591.
  • Wilson G, Ye Z, Xie H, Vahl S, Dawson E, Rowlen K, Xing Z. Automated interpretation of influenza hemagglutination inhibition (HI) assays: is plate tilting necessary? PLoS ONE. 2017;12:e0179939. doi:10.1371/journal.pone.0179939.
  • Hobson D, Curry RL, Beare AS, Ward-Gardner A. The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses. J Hyg (Lond). 1972;70:767–77. doi:10.1017/S0022172400022610.
  • Benoit A, Beran J, Devaster JM, Esen M, Launay O, Leroux-Roels G, McElhaney JE, Oostvogels L, van Essen GA, Gaglani M, et al. Hemagglutination inhibition antibody titers as a correlate of protection against seasonal A/H3N2 influenza disease. Open Forum Infect Dis. 2015;2(2):ofv067. doi:10.1093/ofid/ofv067.
  • de Jong JC, Palache AM, Beyer WE, Rimmelzwaan GF, Boon AC, Osterhaus AD. Haemagglutination-inhibiting antibody to influenza virus. Dev Biol. (Basel). 2003;115:63–73.
  • Coudeville L, Bailleux F, Riche B, Megas F, Andre P, Ecochard R. Relationship between haemagglutination-inhibiting antibody titres and clinical protection against influenza: development and application of a bayesian random-effects model. BMC Med Res Methodol. 2010;10:18. doi:10.1186/1471-2288-10-18.
  • Black S, Nicolay U, Vesikari T, Knuf M, Del Giudice G, Della Cioppa G, Tsai T, Clemens R, Rappuoli R. Hemagglutination inhibition antibody titers as a correlate of protection for inactivated influenza vaccines in children. Pediatr Infect Dis J. 2011;30:1081–85. doi:10.1097/INF.0b013e3182367662.
  • Dunning AJ, DiazGranados CA, Voloshen T, Hu B, Landolfi VA, Talbot HK. Correlates of protection against influenza in the elderly: results from an influenza vaccine efficacy trial. Clin Vaccine Immunol. 2016;23(3):228–35. doi:10.1128/CVI.00604-1519.
  • Mögling R, Richard MJ, Vliet SV, Beek RV, Schrauwen EJA, Spronken MI, Rimmelzwaan GF, Fouchier RAM. Neuraminidase-mediated haemagglutination of recent human influenza A(H3N2) viruses is determined by arginine 150 flanking the neuraminidase catalytic site. J Gen Virol. 2017;98:1274–81. doi:10.1099/jgv.0.000809.
  • Li CK, Rappuoli R, Xu X-N. Correlates of protection against influenza infection in humans–on the path to a universal vaccine? Curr Opin Immunol. 2013;25:470–76. doi:10.1016/j.coi.2013.07.005.
  • Grund S, Adams O, Wahlisch S, Schweiger B. Comparison of hemagglutination inhibition assay, an ELISA-based micro-neutralization assay and colorimetric microneutralization assay to detect antibody responses to vaccination against influenza A H1N1 2009 virus. J Virol Methods. 2011;171:369–73. doi:10.1016/j.jviromet.2010.11.024.
  • Stephenson I, Heath A, Major D, Newman RW, Hoschler K, Junzi W, Katz JM, Weir JP, Zambon MC, Wood JM. Reproducibility of serologic assays for influenza virus A (H5N1). Emerg Infect Dis. 2009;15:1250–59. doi:10.3201/eid1508.081754.
  • Gauger PC, Vincent AL. Serum virus neutralization assay for detection and quantitation of serum-neutralizing antibodies to influenza A virus in swine. Methods Mol Biol. 2014;1161:313–24. doi:10.1007/978-1-4939-0758-8_26.
  • Mohn KG, Smith I, Sjursen H, Cox RJ. Immune responses after live attenuated influenza vaccination. Hum Vaccin Immunother. 2018;14:571–78. doi:10.1080/21645515.2017.1377376.
  • Gorse GJ, Belshe RB. Enhancement of anti-influenza A virus cytotoxicity following influenza A virus vaccination in older, chronically ill adults. J Clin Microbiol. 1990;28:2539–50.
  • Hoft DF, Babusis E, Worku S, Spencer CT, Lottenbach K, Truscott SM, Abate G, Sakala IG, Edwards KM, Creech CB, et al. Live and inactivated influenza vaccines induce similar humoral responses, but only live vaccines induce diverse T-cell responses in young children. J Infect Dis. 2011;204(6):845–53. doi:10.1093/infdis/jir436.
  • Hoft DF, Lottenbach KR, Blazevic A, Turan A, Blevins TP, Pacatte TP, Yu Y, Mitchell MC, Hoft SG, Belshe RB. Comparisons of the humoral and cellular immune responses induced by live attenuated influenza vaccine and inactivated influenza vaccine in adults. Clin Vaccine Immunol. 2017;24(1). doi:10.1128/CVI.00414-16.
  • Belshe RB, Edwards KM, Vesikari T, Black SV, Walker RE, Hultquist M, Kemble G, Connor EM. CAIV-T comparative efficacy study group. Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med. 2007;356(7):685–96. doi:10.1056/NEJMoa065368.
  • Schenkel JM, Masopust D. Tissue-resident memory T cells. Immunity. 2014;41:886–97. doi:10.1016/j.immuni.2014.12.007.
  • Wen F, Guo J, Huang S. A meta-analysis identified genes responsible for distinct immune responses to trivalent inactivated and live attenuated influenza vaccines. J Cell Physiol. Sep 10 2018. doi: 10.1002/jcp.2732
  • Wang B, Russell ML, Brewer A, Newton J, Singh P, Ward BJ, Loeb M. Single radial haemolysis compared to haemagglutinin inhibition and microneutralization as a correlate of protection against influenza A H3N2 in children and adolescents. Influenza Other Respir Viruses. 2017;11:283–88. doi:10.1111/irv.12450.
  • Reber A, Katz J. Immunological assessment of influenza vaccines and immune correlates of protection. Expert Rev Vaccines. 2013;12:519–36. doi:10.1586/erv.13.35.
  • [accessed 2018 Dec 02] www.who.int/immunization/research/meetings_workshops/Jackie_Katz_Chicago_August_2016.pdf
  • Tsang TK, Cauchemez S, Perera RAPM, Freeman G, Fang VJ, Ip DK, Leung GM, Malik Peiris JS, Cowling BJ. Association between antibody titers and protection against influenza virus infection within households. J Infect Dis. 2014;210:684–92. doi:10.1093/infdis/jiu186.
  • Gijzen K, Liu WM, Visontai I, Oftung F, van der Werf S, Korsvold GE, Pronk I, Aaberge IS, Tütto A, Jankovics I, et al. Standardization and validation of assays determining cellular immune responses against influenza. Vaccine. 2010;28:3416–22. doi:10.1016/j.vaccine.2010.02.076.
  • Govaert TM, Thijs CT, Masurel N, Sprenger MJ, Dinant GJ, Knottnerus JA. The efficacy of influenza vaccination in elderly individuals. A randomized double-blind placebo-controlled trial. JAMA. 1994;272:1661–65.
  • Murasko DM, Bernstein ED, Gardner EM, Gross P, Munk G, Dran S, Abrutyn E. Role of humoral and cell-mediated immunity in protection from infuenza disease after immunization of healthy elderly. Exp Gerontol. 2002;37:427–39.
  • Efros RB. Role of T lymphocyte replicative senescence in vaccine efficacy. Vaccine. 2007;25(4):599–604. doi:10.1016/j.vaccine.2006.08.032.
  • McElhaney JE, Effros RB. Immunosenescence: what does it mean to health outcomes in older adults? Curr Opin Immunol. 2009;21(4):418–24. doi:10.1016/j.coi.2009.05.023.
  • McElhaney JE. Prevention of infectious diseases in older adults through immunization: the challenge of the senescent immune response. Expert Rev Vaccines. 2009;8(5):593–606. doi:10.1586/erv.09.12.
  • Fuentes E, Fuentes M, Alarcón M, Palomo I. Immune system dysfunction in the elderly. An Acad Bras Cienc. 2017;89(1):285–99. doi:10.1590/0001-3765201720160487.
  • Shahid Z, Kleppinger A, Gentleman B, Falsey AR, McElhaney JE. Clinical and immunologic predictors of influenza illness among vaccinated older adults. Vaccine. 2010;28:6145–51. doi:10.1016/j.vaccine.2010.07.036.
  • McElhaney JE, Kuchel GA, Zhou X, Swain SL, Haynes L. T-cell immunity to influenza in older adults: a pathophysiological framework for development of more effective vaccines. Front Immunol. 2016;7:41. doi:10.3389/fimmu.2016.00041.
  • Andrew MK, Bowles SK, Pawelec G, Haynes L, Kuchel GA, McNeil SA, McElhaney JE. Influenza vaccination in older adults: recent innovations and practical applications. Drugs Aging. Nov 9 2018. doi: 10.1007/s40266-018-0597-4
  • McElhaney JE, Xie D, Hager WD, Barry MB, Wang Y, Kleppinger A, Ewen C, Kane KP, Bleackley RC. T cell responses are better correlates of vaccine protection in the elderly. J Immunol. 2006;176:6333–39.
  • McElhaney JE, Ewen C, Zhou X, Kane KP, Xie D, Hager WD, Barry MB, Kleppinger A, Wang Y, Bleackley RC, et al. Correlates with protection and enhanced CTL response to influenza vaccination in older adults. Vaccine. 2009;27(18):2418–25. doi:10.1016/j.vaccine.2009.01.136.
  • Berlanda Scorza F, Tsvetnitsky V, Donnellym JJ. Universal influenza vaccines: shifting to better vaccines. Vaccine. 2016;34:2926–33. doi:10.1016/j.vaccine.2016.03.085.
  • Wilkinson TM, Li CK, Chui CS, Huang AK, Perkins M, Liebner JC, Lambkin-Williams R, Gilbert A, Oxford J, Nicholas B, et al. Preexisting influenza-specific CD4+ T cells correlate with disease protec-tion against influenza challenge in humans. Nat Med. 2012;18:274–80. doi:10.1038/nm.2612.
  • Sridhar S, Begom S, Bermingham A, Hoschler K, Adamson W, Carman W, Bean T, Barclay W, Deeks JJ, Lalvani A. Cellular immune correlates of protection against symptomatic pandemic influenza. Nat Med. 2013;19:1305–12. doi:10.1038/nm.3350.
  • Neidich SD, Green WD, Rebeles J, Karlsson EA, Schultz-Cherry S, Noah TL, Chakladar S, Hudgens MG, Weir SS, Beck MA. Increased risk of influenza among vaccinated adults who are obese. Int J Obes (Lond). 2017;41:1324–30. doi:10.1038/ijo.2017.131.
  • Karlsson EA, Hertz T, Johnson C, Mehle A, Krammer F, Schultz-Cherry S. Obesity outweighs protection conferred by adjuvanted influenza vaccination. MBio. 2016;7:e01144–16. doi:10.1128/mBio.01144-16.
  • Thomas PG, Keating R, Hulse-Post DJ, Doherty PC. Cell-mediated protection in influenza infection. Emerg Infect Dis. 2006;12:48–54. doi:10.3201/eid1201.051237.
  • Querec TD, Akondy RS, Lee EK, Cao W, Nakaya HI, Teuwen D, Pirani A, Gernert K, Deng J, Marzolf B, et al. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol. 2009;10:116–25. doi:10.1038/ni.1688.
  • Slifka MK, Amanna I. How advances in immunology provide insight into improving vaccine efficacy. Vaccine. 2014;32:2948–57. doi:10.1016/j.vaccine.2014.03.078.
  • Coughlan L, Lambe T. Measuring cellular immunity to influenza: methods of detection, applications and challenges. Vaccines (Basel). 2015;3:293–319. doi:10.3390/vaccines3020293.
  • Richards KA, Topham D, Chaves FA, Sant AJ. Cutting edge: CD4 T cells generated from encounter with seasonal influenza viruses and vaccines have broad protein specificity and can directly recognize naturally generated epitopes derived from the live pandemic H1N1 virus. J Immunol. 2010;185:4998–5002. doi:10.4049/jimmunol.1001395.
  • Tu W, Mao H, Zheng J, Liu Y, Chiu SS, Qin G, Chan PL, Lam KT, Guan J, Zhang L, et al. Cytotoxic T lymphocytes established by seasonal human influenza cross-react against 2009 pandemic H1N1 influenza virus. J Virol. 2010;84:6527–35. doi:10.1128/JVI.00519-10.
  • McKinstry KK, Strutt TM, Swain SL. Hallmarks of CD4 T cell immunity against influenza. J Intern Med. 2011;269:507–18. doi:10.1111/j.1365-2796.2011.02367.x.
  • Schmidt T, Dirks J, Enders M, Gärtner BC, Uhlmann-Schiffler H, Sester U, Sester M. CD4+ T-cell immunity after pandemic influenza vaccination cross-reacts with seasonal antigens and functionally differs from active influenza infection. Eur J Immunol. 2012;42:1755–66. doi:10.1002/eji.201242393.
  • Suni MA, Picker LJ, Maino VC. Detection of antigen-specific T cell cytokine expression in whole blood by flow cytometry. J. Immunol Methods. 1998;212:89–98. doi:10.1016/S0022-1759(98)00004-0.
  • Nomura LE, Walker JM, Maecker HT. Optimization of whole blood antigen-specific cytokine assays for CD4+ T cells. Cytometry. 2000;40:60–68. doi:10.1002/(ISSN)1097-0320.
  • Waldrop SL, Pitcher CJ, Peterson DM, Maino VC, Picker LJ. Determination of antigen-specific memory/effector CD4+ T cell frequencies by flow cytometry: evidence for a novel, antigen-specific homeostatic mechanism in HIV-associated immunodeficiency. J Clin Invest. 1997;99:1739–50. doi:10.1172/JCI119338.
  • De Rosa SC, Lu FX, Yu J, Perfetto SP, Falloon J, Moser S, Evans TG, Koup R, Miller CJ, Roederer M. Vaccination in humans generates broad T cell cytokine responses. J Immunol. 2004;173:5372–80. doi:10.4049/jimmunol.173.9.5372.
  • Smits K, Pottier G, Smet J, Dirix V, Vermeulen F, De Schutter I, Carollo M, Locht C, Ausiello CM, Mascart F. Different T cell memory in preadolescents after whole-cell or acellular pertussis vaccination. Vaccine. 2013;32:111–18. doi:10.1016/j.vaccine.2013.10.056.
  • Maecker HT, Rinfret A, D’Souza P, Darden J, Roig E, Landry C, Hayes P, Birungi J, Anzala O, Garcia M, et al. Standardization of cytokine flow cytometry assays. BMC Immunol. 2005;6:13. doi:10.1186/1471-2172-6-13.
  • He XS, Holmes TH, Zhang C, Mahmood K, Kemble GW, Lewis DB, Dekker CL, Greenberg HB, Arvin AM. Cellular immune responses in children and adults receiving inactivated or live attenuated influenza vaccines. J Virol. 2006;80(23):11756–66. doi:10.1128/JVI.01460-06.
  • Basha S, Hazenfeld S, Brady RC, Subbramanian RA. Comparison of antibody and T-cell responses elicited by licensed inactivated- and live-attenuated influenza vaccines against H3N2 hemagglutinin. Hum Immunol. 2011;72(6):463–69. doi:10.1016/j.humimm.2011.03.001.
  • Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations. Annu Rev Immunol. 2010;28:445–89. doi:10.1186/1471-2172-6-13.
  • Mittrucker HW, Visekruna A, Huber M. Heterogeneity in the differentiation and function of CD8+ T cells. Arch Immunol Ther Exp (Warsz.). 2014;62:449–58. doi:10.1007/s00005-014-0293-y.
  • Zhou L, Chong MM, Littman DR. Plasticity of CD4+ T cell lineage differentiation. Immunity. 2009;30:646–55. doi:10.1016/j.immuni.2009.05.001.
  • Betts MR, Brenchley JM, Price DA, De Rosa SC, Douek DC, Roederer M, Koup RA. Sensitive and viable identification of antigen-specific CD8+ T cells by a flow cytometric assay for degranulation. J Immunol Methods. 2003;281:65–78.
  • Maecker HT. Multiparameter flow cytometry monitoring of T cell responses. Methods Mol Biol. 2009;485:375–91. doi:10.1007/978-1-59745-170-3_25.
  • Mei HE, Yoshida T, Sime W, Hiepe F, Thiele K, Manz RA, Radbruch A, Dörner T. Blood-bornehuman plasma cells in steady state are derived from mucosal immuneresponses. Blood. 2009;113:2461–69. doi:10.1182/blood-2008-04-153544.
  • Cox RJ, Brokstad KA, Zuckerman MA, Wood JM, Haaheim LR, Oxford JS. Anearly humoral immune response in peripheral blood following parenteralinactivated influenza vaccination. Vaccine. 1994;12:993–99.
  • Wrammert J, Smith K, Miller J, Langley WA, Kokko K, Larsen C, Zheng NY, Mays I, Garman L, Helms C, et al. Rapidcloning of high-affinity human monoclonal antibodies against influenza virus. Nature. 2008;453:667–71. doi:10.1038/nature06890.
  • Halliley JL, Kyu S, Kobie JJ, Walsh EE, Falsey AR, Randall TD, Treanor J, Feng C, Sanz I, Lee FE. Peak frequen-cies of circulating human influenza-specific antibody secreting cells correlate with serum antibody response after immunization. Vaccine. 2010;28:3582–87. doi:10.1016/j.vaccine.2010.02.088.
  • He XS, Sasaki S, Narvaez CF, Zhang C, Liu H, Woo JC, Kemble GW, Dekker CL, Davis MM, Greenberg HB. Plasmablast-derivedpolyclonal antibody response after influenza vaccination. J Immunol Methods. 2011;365:67–75. doi:10.1016/j.jim.2010.12.008.
  • Nakaya HI, Wrammert J, Lee EK, Racioppi L, Marie-Kunze S, Haining WN, Means AR, Kasturi SP, Khan N, Li GM, et al. Systems biology of vaccination for seasonal influenza in humans. Nat Immunol. 2011;12:786–95. doi:10.1038/ni.2067.
  • Jürchott K, Schulz AR, Bozzetti C, Pohlmann D, Stervbo U, Warth S, Mälzer JN, Waldner J, Schweiger B, Olek S, et al. Highly predictive model for a protective immune response to the A(H1N1)pdm2009 influenza strain after seasonal vaccination. PLoS One. 2016;11:e0150812. doi:10.1371/journal.pone.0150812.
  • Kreijtz JHCM, Fouchier RAM, Rimmelzwaan GF. Immune responses to influenza virus infection. Virus Res. 2011;162:19–30. doi:10.1016/j.virusres.2011.09.022.
  • Nayak JL, Fitzgerald TF, Richards K, Yang H, Treanor JJ, Sant AJ. CD4+ T-cell expansion predicts neutralizing antibody responses to monovalent, inactivated 2009 pandemic influenza A(H1N1) virus subtype H1N1 vaccine. J Infect Dis. 2013;207:297–305. doi:10.1093/infdis/jis684.
  • Tebas P, Frank I, Lewis M, Quinn J, Zifchak L, Thomas A, Kenney T, Kappes R, Wagner W, Maffei K, et al. Poor immunogenicity of the H1N1 2009 vaccine in well controlled HIV-infected individuals. Aids. 2010;24:2187–92. doi:10.1097/QAD.0b013e32833c6d5c.
  • Tsang JS, Schwartzberg PL, Kotliarov Y, Biancotto A, Xie Z, Germain RN, Wang E, Olnes MJ, Narayanan M, Golding H, et al. Global analyses of human immune variation reveal baseline predictors of postvaccination responses. Cell. 2014;157:499–513. doi:10.1016/j.cell.2014.03.031.
  • Mbawuike IN, Atmar RL, Patel SM, Corry DB, Winokur PL, Brady RC, Chen WH, Edwards KM, Creech CB, Walter EB Jr, et al. Cell mediated immune responses following revaccination with an influenza A/H5N1 vaccine. Vaccine. 2016;34:547–54. doi:10.1016/j.vaccine.2015.11.055.
  • Wright PF, Hoen AG, Ilyushina NA, Brown EP, Ackerman ME, Wieland-Alter W, Connor RI, Jegaskanda S, Rosenberg-Hasson Y, Haynes BC, et al. Correlates of immunity to influenza as determined by challenge of children with live, attenuated influenza vaccine. Open Forum Infect Dis. 2016;3:ofw108. doi:10.1093/ofid/ofw108.
  • He W, Mullarkey CE, Duty JA, Moran TM, Palese P, Miller MS. Broadly neutralizing anti-influenza virus antibodies: enhancement of neutralizing potency in polyclonal mixtures and IgA backbones. J Virol. 2015;89:3610–18. doi:10.1128/JVI.03099-14.
  • He W, Mullarkey CE, Miller MS. Measuring the neutralization potency of influenza A virus hemagglutinin stalk/stem-binding antibodies in polyclonal preparations by microneutralization assay. Methods. 2015;90:95–100. doi:10.1016/j.ymeth.2015.04.037.
  • Verbonitz MW, Ennis FA, Hicks JT, Albrecht P. Hemagglutinin-specific complement-dependent cytolytic antibody response to influenza infection. J Exp Med. 1978;147:265–70. doi:10.1084/jem.147.1.265.
  • Quinnan GV, Ennis FA, Tuazon CU, Wells MA, Butchko GM, Armstrong R, McLaren C, Manischewitz JF, Kiley S. Cytotoxic lymphocytes and antibody-dependent complement-mediated cytotoxicity induced by administration of influenza vaccine. Infect Immun. 1980;30:362–69.
  • O’Brien KB, Morrison TE, Dundore DY, Heise MT, Schultz-Cherry S, Vartanian J-P. A protective role for complement C3 protein during pandemic 2009 H1N1 and H5N1 influenza A virus infection. PLoS One. 2011;6:e17377. doi:10.1371/journal.pone.0017377.
  • Ohta R, Torii Y, Imai M, Kimura H, Okada N, Ito Y. Serum concentrations of complement anaphylatoxins and proinflammatory mediators in patients with 2009 H1N1 influenza. Microbiol Immunol. 2011;55:191–98. doi:10.1111/j.1348-0421.2011.00309.x.
  • Terajima M, Co MD, Cruz J, Ennis FA. High antibody-dependent cellular cytotoxicity antibody titers to H5N1 and H7N9 avian influenza a viruses in healthy US adults and older children. J Infect Dis. 2015;212:1052–60. doi:10.1093/infdis/jiv181.
  • Ana-Sosa-Batiz F, Vanderven H, Jegaskanda S, Johnston A, Rockman S, Laurie K, Barr I, Reading P, Lichtfuss M, Kent SJ. Influenza-specific antibody-dependent phagocytosis. PLoS One. 2016;11:e0154461. doi:10.1371/journal.pone.0154461.
  • Mullarkey CE, Bailey MJ, Golubeva DA, Tan GS, Nachbagauer R, He W, Novakowski KE, Bowdish DM, Miller MS, Palese P. broadly neutralizing hemagglutinin stalk-specific antibodies induce potent phagocytosis of immune complexes by neutrophils in an Fc-dependent manner. mBio. 2016;7:e01624–16. doi:10.1128/mBio.01624-16.
  • DiLillo DJ, Tan GS, Palese P, Ravetch JV. Broadly neutralizing hemagglutinin stalk-specific antibodies require FcgammaR interactions for protection against influenza virus in vivo. Nat Med. 2014;20:143–51. doi:10.1038/nm.3443.
  • Jegaskanda S, Reading PC, Kent SJ. Influenza-specific antibody dependent cellular cytotoxicity: toward a universal influenza vaccine. J Immunol. 2014;193:469–75. doi:10.4049/jimmunol.1400432.
  • Impagliazzo A, Milder F, Kuipers H, Wagner MV, Zhu X, Hoffman RM, van Meersbergen R, Huizingh J, Wanningen P, Verspuij J, et al. A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. Science. 2015;349:1301–06. doi:10.1126/science.aac7263.
  • DiLillo DJ, Palese P, Wilson PC, Ravetch JV. Broadly neutralizing anti-influenza antibodies require Fc receptor engagement for in vivo protection. J Clin Invest. 2016;126:605–10. doi:10.1172/JCI84428.
  • Jegaskanda S, Vanderven HA, Wheatley AK, Kent SJ. Fc or not Fc; that is the question: antibody Fc-receptor interactions are key to universal influenzavaccine design. Hum Vaccin Immunother. 2017;13(6):1–9. doi:10.1080/21645515.2017.1290018.
  • Vanderven HA, Jegaskanda S, Wines BD, Hogarth PM, Carmuglia S, Rockman S, Chung AW, Kent SJ. Antibody-dependent cellular cytotoxicity responses to seasonal influenza vaccination in older adults. J Infect Dis. 2017;217(1):12–23. doi:10.1093/infdis/jix554.
  • Zaritskaya L, Shurin MR, Sayers TJ, Malyguine AM. New flow cytometric assays for monitoring cell-mediated cytotoxicity. Expert Rev Vaccines. 2010;9(6):601–16. doi:10.1586/erv.10.49.
  • Valiathan R, Lewis JE, Melillo AB, Leonard S, Ali KH, Asthana D. Evaluation of a flow cytometry-based assay for natural killer cell activity in clinical settings. Scand J Immunol. 2012;75(4):455–62. doi:10.1111/j.1365-3083.2011.02667.x.
  • Memarnejadian A, Meilleur CE, Mazzuca DM, Welch ID, Haeryfar SM. Quantification of alloantibody-mediated cytotoxicity in vivo. Transplantation. 2016;100(5):1041–51. doi:10.1097/TP.0000000000001154.
  • Wines BD, Billings H, Mclean MR, Kent SJ, Hogarth PM. Antibody functional assays as measures of Fc receptor-mediated immunity to HIV - new technologies and their impact on the HIV vaccine field. Curr HIV Res. 2017;15(3):202–15. doi:10.2174/1570162X15666170320112247.