Yonsei Med J.  2013 Mar;54(2):271-282. 10.3349/ymj.2013.54.2.271.

Cross-Protective Immune Responses Elicited by Live Attenuated Influenza Vaccines

Affiliations
  • 1Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Seoul, Korea. blseong@yonsei.ac.kr
  • 2Translational Research Center for Protein Function Control, Yonsei University, Seoul, Korea.

Abstract

The desired effect of vaccination is to elicit protective immune responses against infection with pathogenic agents. An inactivated influenza vaccine is able to induce the neutralizing antibodies directed primarily against two surface antigens, hemagglutinin and neuraminidase. These two antigens undergo frequent antigenic drift and hence necessitate the annual update of a new vaccine strain. Besides the antigenic drift, the unpredictable emergence of the pandemic influenza strain, as seen in the 2009 pandemic H1N1, underscores the development of a new influenza vaccine that elicits broadly protective immunity against the diverse influenza strains. Cold-adapted live attenuated influenza vaccines (CAIVs) are advocated as a more appropriate strategy for cross-protection than inactivated vaccines and extensive studies have been conducted to address the issues in animal models. Here, we briefly describe experimental and clinical evidence for cross-protection by the CAIVs against antigenically distant strains and discuss possible explanations for cross-protective immune responses afforded by CAIVs. Potential barriers to the achievement of a universal influenza vaccine are also discussed, which will provide useful guidelines for future research on designing an ideal influenza vaccine with broad protection without causing pathogenic effects such as autoimmunity or attrition of protective immunity against homologous infection.

Keyword

Influenza live attenuated vaccine; cross-protection; cold-adaptation; universal vaccine

MeSH Terms

Adaptive Immunity
Antigens, Viral/immunology
*Cross Protection
Genome, Viral
Humans
Immunity, Innate
Influenza Vaccines/*immunology/therapeutic use
Influenza, Human/*prevention & control
Orthomyxoviridae/genetics/immunology
Vaccines, Attenuated
Antigens, Viral
Influenza Vaccines
Vaccines, Attenuated

Figure

  • Fig. 1 T cell Immunodominance. Virus-specific CTLs recognize the complex of the viral peptide and MHC class-I molecule presented on the membrane of the infected cells. Some peptides generate strong signals and thereby lead to the robust clonal expansion of the responding CTLs (immunodominant), some generate weak (subdominant) signals, and others barely generate a signal (cryptic) only detectable in the absence of the others. The hierarchy of the T cell immunodominance shaped by primary exposure to a virus varies upon a subsequent infection with heterologous virus. CTL, cytotoxic T lymphocyte; TCR, T cell receptor; MHC, major histocompatiblity complex.


Reference

1. Englund JA, Champlin RE, Wyde PR, Kantarjian H, Atmar RL, Tarrand J, et al. Common emergence of amantadine- and rimantadine-resistant influenza A viruses in symptomatic immunocompromised adults. Clin Infect Dis. 1998. 26:1418–1424.
Article
2. de Jong MD, Tran TT, Truong HK, Vo MH, Smith GJ, Nguyen VC, et al. Oseltamivir resistance during treatment of influenza A (H5N1) infection. N Engl J Med. 2005. 353:2667–2672.
Article
3. Wiley DC, Wilson IA, Skehel JJ. Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. Nature. 1981. 289:373–378.
Article
4. de Jong JC, Claas EC, Osterhaus AD, Webster RG, Lim WL. A pandemic warning? Nature. 1997. 389:554.
Article
5. Claas EC, Osterhaus AD, van Beek R, De Jong JC, Rimmelzwaan GF, Senne DA, et al. Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet. 1998. 351:472–477.
Article
6. Subbarao K, Klimov A, Katz J, Regnery H, Lim W, Hall H, et al. Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness. Science. 1998. 279:393–396.
Article
7. Herfst S, Schrauwen EJ, Linster M, Chutinimitkul S, de Wit E, Munster VJ, et al. Airborne transmission of influenza A/H5N1 virus between ferrets. Science. 2012. 336:1534–1541.
Article
8. Russell CA, Fonville JM, Brown AE, Burke DF, Smith DL, James SL, et al. The potential for respiratory droplet-transmissible A/H5N1 influenza virus to evolve in a mammalian host. Science. 2012. 336:1541–1547.
Article
9. Imai M, Watanabe T, Hatta M, Das SC, Ozawa M, Shinya K, et al. Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature. 2012. 486:420–428.
Article
10. Garten RJ, Davis CT, Russell CA, Shu B, Lindstrom S, Balish A, et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science. 2009. 325:197–201.
11. Shinde V, Bridges CB, Uyeki TM, Shu B, Balish A, Xu X, et al. Triple-reassortant swine influenza A (H1) in humans in the United States, 2005-2009. N Engl J Med. 2009. 360:2616–2625.
Article
12. Octaviani CP, Ozawa M, Yamada S, Goto H, Kawaoka Y. High level of genetic compatibility between swine-origin H1N1 and highly pathogenic avian H5N1 influenza viruses. J Virol. 2010. 84:10918–10922.
13. Cline TD, Karlsson EA, Freiden P, Seufzer BJ, Rehg JE, Webby RJ, et al. Increased pathogenicity of a reassortant 2009 pandemic H1N1 influenza virus containing an H5N1 hemagglutinin. J Virol. 2011. 85:12262–12270.
Article
14. Welsh RM, Che JW, Brehm MA, Selin LK. Heterologous immunity between viruses. Immunol Rev. 2010. 235:244–266.
Article
15. Bender BS, Croghan T, Zhang L, Small PA Jr. Transgenic mice lacking class I major histocompatibility complex-restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge. J Exp Med. 1992. 175:1143–1145.
Article
16. Doherty PC. Cytotoxic T cell effector and memory function in viral immunity. Curr Top Microbiol Immunol. 1996. 206:1–14.
Article
17. Price GE, Ou R, Jiang H, Huang L, Moskophidis D. Viral escape by selection of cytotoxic T cell-resistant variants in influenza A virus pneumonia. J Exp Med. 2000. 191:1853–1867.
Article
18. McMichael AJ, Gotch FM, Noble GR, Beare PA. Cytotoxic T-cell immunity to influenza. N Engl J Med. 1983. 309:13–17.
Article
19. Selin LK, Vergilis K, Welsh RM, Nahill SR. Reduction of otherwise remarkably stable virus-specific cytotoxic T lymphocyte memory by heterologous viral infections. J Exp Med. 1996. 183:2489–2499.
Article
20. Selin LK, Lin MY, Kraemer KA, Pardoll DM, Schneck JP, Varga SM, et al. Attrition of T cell memory: selective loss of LCMV epitope-specific memory CD8 T cells following infections with heterologous viruses. Immunity. 1999. 11:733–742.
21. Brehm MA, Pinto AK, Daniels KA, Schneck JP, Welsh RM, Selin LK. T cell immunodominance and maintenance of memory regulated by unexpectedly cross-reactive pathogens. Nat Immunol. 2002. 3:627–634.
Article
22. Treanor JJ, Wilkinson BE, Masseoud F, Hu-Primmer J, Battaglia R, O'Brien D, et al. Safety and immunogenicity of a recombinant hemagglutinin vaccine for H5 influenza in humans. Vaccine. 2001. 19:1732–1737.
Article
23. Nicholson KG, Colegate AE, Podda A, Stephenson I, Wood J, Ypma E, et al. Safety and antigenicity of non-adjuvanted and MF59-adjuvanted influenza A/Duck/Singapore/97 (H5N3) vaccine: a randomised trial of two potential vaccines against H5N1 influenza. Lancet. 2001. 357:1937–1943.
Article
24. Aymard M, Valette M, Lina B, Thouvenot D. Surveillance and impact of influenza in Europe. Groupe Regional d'Observation de la Grippe and European Influenza Surveillance Scheme. Vaccine. 1999. 17:Suppl 1. S30–S41.
25. Klimov A, Simonsen L, Fukuda K, Cox N. Surveillance and impact of influenza in the United States. Vaccine. 1999. 17:Suppl 1. S42–S46.
Article
26. Steel J, Lowen AC, Wang TT, Yondola M, Gao Q, Haye K, et al. Influenza virus vaccine based on the conserved hemagglutinin stalk domain. MBio. 2010. 1:pii: e00018-10.
Article
27. Ulmer JB, Fu TM, Deck RR, Friedman A, Guan L, DeWitt C, et al. Protective CD4+ and CD8+ T cells against influenza virus induced by vaccination with nucleoprotein DNA. J Virol. 1998. 72:5648–5653.
Article
28. Fu TM, Guan L, Friedman A, Schofield TL, Ulmer JB, Liu MA, et al. Dose dependence of CTL precursor frequency induced by a DNA vaccine and correlation with protective immunity against influenza virus challenge. J Immunol. 1999. 162:4163–4170.
29. Ulmer JB, Deck RR, Dewitt CM, Donnhly JI, Liu MA. Generation of MHC class I-restricted cytotoxic T lymphocytes by expression of a viral protein in muscle cells: antigen presentation by non-muscle cells. Immunology. 1996. 89:59–67.
Article
30. Klinman DM, Takeno M, Ichino M, Gu M, Yamshchikov G, Mor G, et al. DNA vaccines: safety and efficacy issues. Springer Semin Immunopathol. 1997. 19:245–256.
Article
31. Bodewes R, Fraaij PL, Geelhoed-Mieras MM, van Baalen CA, Tiddens HA, van Rossum AM, et al. Annual vaccination against influenza virus hampers development of virus-specific CD8+ T cell immunity in children. J Virol. 2011. 85:11995–12000.
Article
32. Bodewes R, Kreijtz JH, Baas C, Geelhoed-Mieras MM, de Mutsert G, van Amerongen G, et al. Vaccination against human influenza A/H3N2 virus prevents the induction of heterosubtypic immunity against lethal infection with avian influenza A/H5N1 virus. PLoS One. 2009. 4:e5538.
Article
33. Bodewes R, Kreijtz JH, Geelhoed-Mieras MM, van Amerongen G, Verburgh RJ, van Trierum SE, et al. Vaccination against seasonal influenza A/H3N2 virus reduces the induction of heterosubtypic immunity against influenza A/H5N1 virus infection in ferrets. J Virol. 2011. 85:2695–2702.
Article
34. Bodewes R, Kreijtz JH, Hillaire ML, Geelhoed-Mieras MM, Fouchier RA, Osterhaus AD, et al. Vaccination with whole inactivated virus vaccine affects the induction of heterosubtypic immunity against influenza virus A/H5N1 and immunodominance of virus-specific CD8+ T-cell responses in mice. J Gen Virol. 2010. 91(Pt 7):1743–1753.
Article
35. Suguitan AL Jr, McAuliffe J, Mills KL, Jin H, Duke G, Lu B, et al. Live, attenuated influenza A H5N1 candidate vaccines provide broad cross-protection in mice and ferrets. PLoS Med. 2006. 3:e360.
Article
36. Fan S, Gao Y, Shinya K, Li CK, Li Y, Shi J, et al. Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates. PLoS Pathog. 2009. 5:e1000409.
37. Desheva JA, Lu XH, Rekstin AR, Rudenko LG, Swayne DE, Cox NJ, et al. Characterization of an influenza A H5N2 reassortant as a candidate for live-attenuated and inactivated vaccines against highly pathogenic H5N1 viruses with pandemic potential. Vaccine. 2006. 24:6859–6866.
Article
38. Chen GL, Min JY, Lamirande EW, Santos C, Jin H, Kemble G, et al. Comparison of a live attenuated 2009 H1N1 vaccine with seasonal influenza vaccines against 2009 pandemic H1N1 virus infection in mice and ferrets. J Infect Dis. 2011. 203:930–936.
Article
39. Yang P, Duan Y, Wang C, Xing L, Gao X, Tang C, et al. Immunogenicity and protective efficacy of a live attenuated vaccine against the 2009 pandemic A H1N1 in mice and ferrets. Vaccine. 2011. 29:698–705.
Article
40. Jang YH, Byun YH, Lee YJ, Lee YH, Lee KH, Seong BL. Cold-adapted pandemic 2009 H1N1 influenza virus live vaccine elicits cross-reactive immune responses against seasonal and H5 influenza A viruses. J Virol. 2012. 86:5953–5958.
Article
41. Murphy BR, Clements ML. The systemic and mucosal immune response of humans to influenza A virus. Curr Top Microbiol Immunol. 1989. 146:107–116.
Article
42. Tumpey TM, Renshaw M, Clements JD, Katz JM. Mucosal delivery of inactivated influenza vaccine induces B-cell-dependent heterosubtypic cross-protection against lethal influenza A H5N1 virus infection. J Virol. 2001. 75:5141–5150.
Article
43. Beyer WE, Palache AM, de Jong JC, Osterhaus AD. Cold-adapted live influenza vaccine versus inactivated vaccine: systemic vaccine reactions, local and systemic antibody response, and vaccine efficacy. A meta-analysis. Vaccine. 2002. 20:1340–1353.
Article
44. Powers DC, Fries LF, Murphy BR, Thumar B, Clements ML. In elderly persons live attenuated influenza A virus vaccines do not offer an advantage over inactivated virus vaccine in inducing serum or secretory antibodies or local immunologic memory. J Clin Microbiol. 1991. 29:498–505.
Article
45. Hillaire ML, Osterhaus AD, Rimmelzwaan GF. Induction of virus-specific cytotoxic T lymphocytes as a basis for the development of broadly protective influenza vaccines. J Biomed Biotechnol. 2011. 2011:939860.
Article
46. Belshe RB, Gruber WC, Mendelman PM, Cho I, Reisinger K, Block SL, et al. Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine. J Pediatr. 2000. 136:168–175.
Article
47. Nichol KL, Mendelman PM, Mallon KP, Jackson LA, Gorse GJ, Belshe RB, et al. Effectiveness of live, attenuated intranasal influenza virus vaccine in healthy, working adults: a randomized controlled trial. JAMA. 1999. 282:137–144.
Article
48. Clover RD, Crawford S, Glezen WP, Taber LH, Matson CC, Couch RB. Comparison of heterotypic protection against influenza A/Taiwan/86 (H1N1) by attenuated and inactivated vaccines to A/Chile/83-like viruses. J Infect Dis. 1991. 163:300–304.
Article
49. Edwards KM, Dupont WD, Westrich MK, Plummer WD Jr, Palmer PS, Wright PF. A randomized controlled trial of cold-adapted and inactivated vaccines for the prevention of influenza A disease. J Infect Dis. 1994. 169:68–76.
Article
50. Ohmit SE, Victor JC, Rotthoff JR, Teich ER, Truscon RK, Baum LL, et al. Prevention of antigenically drifted influenza by inactivated and live attenuated vaccines. N Engl J Med. 2006. 355:2513–2522.
Article
51. Belshe RB, Edwards KM, Vesikari T, Black SV, Walker RE, Hultquist M, et al. Live attenuated versus inactivated influenza vaccine in infants and young children. N Engl J Med. 2007. 356:685–696.
Article
52. Powell TJ, Strutt T, Reome J, Hollenbaugh JA, Roberts AD, Woodland DL, et al. Priming with cold-adapted influenza A does not prevent infection but elicits long-lived protection against supralethal challenge with heterosubtypic virus. J Immunol. 2007. 178:1030–1038.
Article
53. Ding H, Tsai C, Zhou F, Buchy P, Deubel V, Zhou P. Heterosubtypic antibody response elicited with seasonal influenza vaccine correlates partial protection against highly pathogenic H5N1 virus. PLoS One. 2011. 6:e17821.
Article
54. Sandbulte MR, Jimenez GS, Boon AC, Smith LR, Treanor JJ, Webby RJ. Cross-reactive neuraminidase antibodies afford partial protection against H5N1 in mice and are present in unexposed humans. PLoS Med. 2007. 4:e59.
Article
55. van Maurik A, Sabarth N, Dacho HS, Brühl P, Schwendinger M, Crowe BA, et al. Seasonal influenza vaccine elicits heterosubtypic immunity against H5N1 that can be further boosted by H5N1 vaccination. Vaccine. 2010. 28:1778–1785.
Article
56. Shi J, Wen Z, Guo J, Zhang Y, Deng G, Shu Y, et al. Protective efficacy of an H1N1 cold-adapted live vaccine against the 2009 pandemic H1N1, seasonal H1N1, and H5N1 influenza viruses in mice. Antiviral Res. 2012. 93:346–353.
Article
57. WHO/OIE/FAO H5N1 Evolution Working Group. Continued evolution of highly pathogenic avian influenza A (H5N1): updated nomenclature. Influenza Other Respi Viruses. 2012. 6:1–5.
58. WHO/OIE/FAO H5N1 Evolution Working Group. Continuing progress towards a unified nomenclature for the highly pathogenic H5N1 avian influenza viruses: divergence of clade 2.2 viruses. Influenza Other Respi Viruses. 2009. 3:59–62.
59. Gustin KM, Maines TR, Belser JA, van Hoeven N, Lu X, Dong L, et al. Comparative immunogenicity and cross-clade protective efficacy of mammalian cell-grown inactivated and live attenuated H5N1 reassortant vaccines in ferrets. J Infect Dis. 2011. 204:1491–1499.
Article
60. Chen Z, Wang W, Zhou H, Suguitan AL Jr, Shambaugh C, Kim L, et al. Generation of live attenuated novel influenza virus A/California/7/09 (H1N1) vaccines with high yield in embryonated chicken eggs. J Virol. 2010. 84:44–51.
Article
61. Girard MP, Katz JM, Pervikov Y, Hombach J, Tam JS. Report of the 7th meeting on Evaluation of Pandemic Influenza Vaccines in Clinical Trials, World Health Organization, Geneva, 17-18 February 2011. Vaccine. 2011. 29:7579–7586.
Article
62. Chen GL, Lau YF, Lamirande EW, McCall AW, Subbarao K. Seasonal influenza infection and live vaccine prime for a response to the 2009 pandemic H1N1 vaccine. Proc Natl Acad Sci U S A. 2011. 108:1140–1145.
Article
63. Sun K, Ye J, Perez DR, Metzger DW. Seasonal FluMist vaccination induces cross-reactive T cell immunity against H1N1 (2009) influenza and secondary bacterial infections. J Immunol. 2011. 186:987–993.
Article
64. Qiu C, Huang Y, Wang Q, Tian D, Zhang W, Hu Y, et al. Boosting heterosubtypic neutralization antibodies in recipients of 2009 pandemic H1N1 influenza vaccine. Clin Infect Dis. 2012. 54:17–24.
Article
65. Wrammert J, Koutsonanos D, Li GM, Edupuganti S, Sui J, Morrissey M, et al. Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. J Exp Med. 2011. 208:181–193.
Article
66. Jang YH, Seong BL. Principles underlying rational design of live attenuated influenza vaccines. Clin Exp Vaccin Res. 2012. 1:35–49.
Article
67. Murphy KM, Travers P, Walport M, Janeway C. Janeway's Immunobiology. 2008. 7th ed. Garland Science.
68. Yewdell JW, Bennink JR, Smith GL, Moss B. Influenza A virus nucleoprotein is a major target antigen for cross-reactive anti-influenza A virus cytotoxic T lymphocytes. Proc Natl Acad Sci U S A. 1985. 82:1785–1789.
Article
69. Gotch F, McMichael A, Smith G, Moss B. Identification of viral molecules recognized by influenza-specific human cytotoxic T lymphocytes. J Exp Med. 1987. 165:408–416.
Article
70. Tan PT, Khan AM, August JT. Highly conserved influenza A sequences as T cell epitopes-based vaccine targets to address the viral variability. Hum Vaccin. 2011. 7:402–409.
Article
71. Gras S, Kedzierski L, Valkenburg SA, Laurie K, Liu YC, Denholm JT, et al. Cross-reactive CD8+ T-cell immunity between the pandemic H1N1-2009 and H1N1-1918 influenza A viruses. Proc Natl Acad Sci U S A. 2010. 107:12599–12604.
Article
72. Grandea AG 3rd, Olsen OA, Cox TC, Renshaw M, Hammond PW, Chan-Hui PY, et al. Human antibodies reveal a protective epitope that is highly conserved among human and nonhuman influenza A viruses. Proc Natl Acad Sci U S A. 2010. 107:12658–12663.
Article
73. Hendrickson BA, Conner DA, Ladd DJ, Kendall D, Casanova JE, Corthesy B, et al. Altered hepatic transport of immunoglobulin A in mice lacking the J chain. J Exp Med. 1995. 182:1905–1911.
Article
74. Niles MJ, Matsuuchi L, Koshland ME. Polymer IgM assembly and secretion in lymphoid and nonlymphoid cell lines: evidence that J chain is required for pentamer IgM synthesis. Proc Natl Acad Sci U S A. 1995. 92:2884–2888.
Article
75. Renegar KB, Jackson GD, Mestecky J. In vitro comparison of the biologic activities of monoclonal monomeric IgA, polymeric IgA, and secretory IgA. J Immunol. 1998. 160:1219–1223.
76. Carragher DM, Kaminski DA, Moquin A, Hartson L, Randall TD. A novel role for non-neutralizing antibodies against nucleoprotein in facilitating resistance to influenza virus. J Immunol. 2008. 181:4168–4176.
Article
77. Rangel-Moreno J, Carragher DM, Misra RS, Kusser K, Hartson L, Moquin A, et al. B cells promote resistance to heterosubtypic strains of influenza via multiple mechanisms. J Immunol. 2008. 180:454–463.
Article
78. Huber VC, Lynch JM, Bucher DJ, Le J, Metzger DW. Fc receptor-mediated phagocytosis makes a significant contribution to clearance of influenza virus infections. J Immunol. 2001. 166:7381–7388.
Article
79. Jegerlehner A, Schmitz N, Storni T, Bachmann MF. Influenza A vaccine based on the extracellular domain of M2: weak protection mediated via antibody-dependent NK cell activity. J Immunol. 2004. 172:5598–5605.
Article
80. Ekiert DC, Bhabha G, Elsliger MA, Friesen RH, Jongeneelen M, Throsby M, et al. Antibody recognition of a highly conserved influenza virus epitope. Science. 2009. 324:246–251.
Article
81. Corti D, Voss J, Gamblin SJ, Codoni G, Macagno A, Jarrossay D, et al. A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science. 2011. 333:850–856.
Article
82. Prabhu N, Prabakaran M, Ho HT, Velumani S, Qiang J, Goutama M, et al. Monoclonal antibodies against the fusion peptide of hemagglutinin protect mice from lethal influenza A virus H5N1 infection. J Virol. 2009. 83:2553–2562.
Article
83. Krause JC, Tsibane T, Tumpey TM, Huffman CJ, Basler CF, Crowe JE Jr. A broadly neutralizing human monoclonal antibody that recognizes a conserved, novel epitope on the globular head of the influenza H1N1 virus hemagglutinin. J Virol. 2011. 85:10905–10908.
Article
84. Whittle JR, Zhang R, Khurana S, King LR, Manischewitz J, Golding H, et al. Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin. Proc Natl Acad Sci U S A. 2011. 108:14216–14221.
85. Lingwood D, McTamney PM, Yassine HM, Whittle JR, Guo X, Boyington JC, et al. Structural and genetic basis for development of broadly neutralizing influenza antibodies. Nature. 2012. 489:566–570.
Article
86. Seo SU, Lee KH, Byun YH, Kweon MN, Seong BL. Immediate and broad-spectrum protection against heterologous and heterotypic lethal challenge in mice by live influenza vaccine. Vaccine. 2007. 25:8067–8076.
Article
87. Bodewes R, Kreijtz JH, Rimmelzwaan GF. Yearly influenza vaccinations: a double-edged sword. Lancet Infect Dis. 2009. 9:784–788.
Article
88. Heikkinen T, Peltola V. Influenza vaccination of children. Lancet Infect Dis. 2009. 9:720–721.
Article
89. Skowronski DM, De Serres G, Crowcroft NS, Janjua NZ, Boulianne N, Hottes TS, et al. Association between the 2008-09 seasonal influenza vaccine and pandemic H1N1 illness during Spring-Summer 2009: four observational studies from Canada. PLoS Med. 2010. 7:e1000258.
Article
90. Yewdell JW, Bennink JR. Immunodominance in major histocompatibility complex class I-restricted T lymphocyte responses. Annu Rev Immunol. 1999. 17:51–88.
Article
91. Haanen JB, Wolkers MC, Kruisbeek AM, Schumacher TN. Selective expansion of cross-reactive CD8(+) memory T cells by viral variants. J Exp Med. 1999. 190:1319–1328.
Article
92. Zhao ZS, Granucci F, Yeh L, Schaffer PA, Cantor H. Molecular mimicry by herpes simplex virus-type 1: autoimmune disease after viral infection. Science. 1998. 279:1344–1347.
Article
93. Tsunoda I, Kuang LQ, Kobayashi-Warren M, Fujinami RS. Central nervous system pathology caused by autoreactive CD8+ T-cell clones following virus infection. J Virol. 2005. 79:14640–14646.
Article
94. Chen AT, Cornberg M, Gras S, Guillonneau C, Rossjohn J, Trees A, et al. Loss of anti-viral immunity by infection with a virus encoding a cross-reactive pathogenic epitope. PLoS Pathog. 2012. 8:e1002633.
Article
Full Text Links
  • YMJ
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr