A history of the development of Brucella vaccines

BioMed Research International

Volumn 2013, Issue , 2013, Pages

  Avila Calderón, Eric Daniel ^a   Lopez Merino, Ahidé ^a   Sriranganathan, Nammalwar ^b   Boyle, Stephen M ^b   Contreras Rodríguez, Araceli ^a  

^a INSTITUTO POLITÉCNICO NACIONAL   (Mexico)

^b CENTER FOR MOLECULAR MEDICINE AND INFECTIOUS DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BRUCELLA VACCINE; DNA VACCINE; GAMMA INTERFERON; INTERLEUKIN 12; LIVE VACCINE; OUTER MEMBRANE PROTEIN; RECOMBINANT PROTEIN; SUBUNIT VACCINE; TUMOR NECROSIS FACTOR ALPHA;

ANTIBODY RESPONSE; ANTIGENICITY; BACTERIAL STRAIN; BRUCELLOSIS; CYTOKINE PRODUCTION; DISEASE ERADICATION; DRUG DEVELOPMENT; DRUG RESEARCH; HEALTH PROGRAM; IMMUNE RESPONSE; INFECTION PREVENTION; REVIEW; TH1 CELL; VACCINATION; ANIMAL; HISTORY; HUMAN; IMMUNOLOGY;

ANIMALIA; BRUCELLA;

ANIMALS; BRUCELLA VACCINE; BRUCELLOSIS; DISEASE ERADICATION; HISTORY, 20TH CENTURY; HUMANS; VACCINES, SUBUNIT;

EID: 84879400210     PISSN: 23146133     EISSN: 23146141     Source Type: Journal    
DOI: 10.1155/2013/743509     Document Type: Review

References (75)

1. Pappas G., Papadimitriou P., Akritidis N., Christou L., Tsianos E. V., The new global map of human brucellosis. Lancet Infectious Diseases 2006 6 2 91 99 2-s2.0-31344450203 10.1016/S1473-3099(06)70382-6 (Pubitemid 43138907)
2. Luna-Martínez J. E., Mejía-Terán C., Brucellosis in Mexico: current status and trend. Veterinary Microbiology 2002 90 1-4 19 30 10.1016/S0378-1135(02)00241-9 (Pubitemid 35279865)
3. Ariza J., Bosilkovski M., Cascio A., Colmenero J. D., Corbel M. J., Falagas M. E., Memish Z. A., Roushan M. R. H., Rubinstein E., Sipsas N. V., Solera J., Young E. J., Pappas G., Perspectives for the treatment of brucellosis in the 21st century: the Ioannina recommendations. PLoS Medicine 2007 4 12, article e317 2-s2.0-38048999578 10.1371/journal.pmed.0040317
4. Nicoletti P., Nielsen K., Duncan J. R., Vaccination. Animal Brucellosis 1990 Boca Raton, Fla, USA CRC Press 284 299
5. Schurig G. G., Sriranganathan N., Corbel M. J., Brucellosis vaccines: past, present and future. Veterinary Microbiology 2002 90 1-4 479 496 2-s2.0-0037146685 10.1016/S0378-1135(02)00255-9 (Pubitemid 35282500)
6. Roux J., Madkour M. M., Brucella vaccines in humans. Brucellosis 1989 London, UK Butterworths 244 249
7. Plommet M., Renoux G., Philppon A., Lorentz C., Gestin J., Brucellose experimentale. I. Comparison de l'efficacite des vaccines B19 and H38 vaccine. Annales de Recherches Veterinaires (Paris) 1970 1 189 201
8. Montaraz J. A., Winter A. J., Comparison of living and nonliving vaccines for Brucella abortus in BALB/c mice. Infection and Immunity 1986 53 2 245 251 2-s2.0-0022468107 (Pubitemid 16073848)
9. Winter A. J., Rowe G. E., Comparative immune responses to native cell envelope antigens and the hot sodium dodecyl sulfate insoluble fraction (PG) of Brucella abortus in cattle and mice. Veterinary Immunology and Immunopathology 1988 18 2 149 163 2-s2.0-0023936644 10.1016/0165-2427(88)90057-8
10. Roux J., Serre A., Prophylaxie individuelle et vaccination contre les brucelloses humaines par une fraction antigénique de Brucella melitensis (complexe proteines-glycoproteines-glycosaminopeptides). Revue d'épidémiologie, Médecine Sociale et Santé Publique 1971 19 503 516
11. Sterne M., Trim G., Broughton E. S., Immunisation of laboratory animals and cattle with non-agglutinogenic extracts of Brucella abortus strain 45-20. Journal of Medical Microbiology 1971 4 2 185 194 2-s2.0-0015063554
12. Dzata G. K., Confer A. W., Wyckoff J. H., The effects of adjuvants on immune responses in cattle injected with a Brucella abortus soluble antigen. Veterinary Microbiology 1991 29 1 27 48 2-s2.0-0025813041 10.1016/0378-1135(91) 90108-R
13. Pugh G. W., Tabatabai L. B., Variation in Brucella abortus 2308 infection in BALB/c mice induced by prior vaccination with salt-extractable periplasmic proteins from Brucella abortus 19. Infection and Immunity 1996 64 2 548 556 2-s2.0-0030061539
14. Stevens M. G., Tabatabai L. B., Olsen S. C., Cheville N. F., Immune responses to superoxide dismutase and synthetic peptides of superoxide dismutase in cattle vaccinated with Brucella abortus strain 19 or RB51. Veterinary Microbiology 1994 41 4 383 389 2-s2.0-0028105963 10.1016/0378-1135(94)90034-5 (Pubitemid 24293265)
15. Tabatabai L. B., Pugh G. W. Jr., Stevens M. G., Phillips M., McDonald T. J., Monophosphoryl lipid A-induced immune enhancement of Brucella abortus salt-extractable protein and lipopolysaccharide vaccines in BALB/c mice. American Journal of Veterinary Research 1992 53 10 1900 1907 2-s2.0-0026937376
16. Tabatabai L. B., Pugh G. W. Jr., Modulation of immune responses in Balb/c mice vaccinated with Brucella abortus Cu-Zn superoxide dismutase synthetic peptide vaccine. Vaccine 1994 12 10 919 924 2-s2.0-0028109269 10.1016/0264-410X(94)90035-3
17. Desmettre P., Jouber L., Valette L., Roux J., Vaccin de la brucellose humaine obtenu a partir de la fraction phenolo-insoluble de Brucella abortus souche B19. Production, contrôle, standardisation. Developments in Biological Standardization 1984 56 579 586 (Pubitemid 14041384)
18. Roux J., Epidemiology and prevention of brucellosis. Bulletin of the World Health Organization 1979 57 2 179 194 2-s2.0-0018763457 (Pubitemid 9173525)
19. Olsen S. C., Stoffregen W. S., Essential role of vaccines in brucellosis control and eradication programs for livestock. Expert Review of Vaccines 2005 4 6 915 928 2-s2.0-29944447211 10.1586/14760584.4.6.915 (Pubitemid 43040911)
20. Marzetti S., Carranza C., Roncallo M., Escobar G. I., Lucero N. E., Recent trends in human Brucellacanis infection. Comparative Immunology, Microbiology and Infectious Disease 2013 36 1 55 61 10.1016/j.cimid.2012.09.002
21. Oliveira S. C., Giambartolomei G. H., Cassataro J., Confronting the barriers to develop novel vaccines against brucellosis. Expert Review of Vaccines 2011 10 9 1291 1305 10.1586/erv.11.110
22. Moriyón I., Grilló M. J., Monreal D., Rough vaccines in animal brucellosis: structural and genetic basis and present status., Veterinary Research 2004 35 1 1 38 10.1051/vetres:2003037 (Pubitemid 38380146)
23. Thomas E. L., Bracewell C. D., Corbel M. J., Characterisation of Brucella abortus strain 19 cultures isolated from vaccinated cattle. Veterinary Record 1981 108 5 90 93 2-s2.0-0019891737
24. Adams L. G., Adams L. G., Development of live Brucella vaccines. Advances of Brucellosis Research 1990 250 256
25. Schurig G. G., Roop R. M., Bagchi T., Boyle S., Buhrman D., Sriranganathan N., Biological properties of RB51; a stable rough strain of Brucella abortus. Veterinary Microbiology 1991 28 2 171 188 2-s2.0-0025729450 10.1016/0378-1135(91)90091-S
26. Vemulapalli R., McQuiston J. R., Schurig G. G., Sriranganathan N., Halling S. M., Boyle S. M., Identification of an IS711 element interrupting the wboA gene of Brucella abortus vaccine strain RB51 and a PCR assay to distinguish strain RB51 from other Brucella species and strains. Clinical and Diagnostic Laboratory Immunology 1999 6 5 760 764 2-s2.0-0032874151 (Pubitemid 29441188)
27. Uzal F. A., Samartino L., Schurig G., Carrasco A., Nielsen K., Cabrera R. F., Taddeo H. R., Effect of vaccination with Brucella abortus strain RB51 on heifers and pregnant cattle. Veterinary Research Communications 2000 24 3 143 151 2-s2.0-0034000262 10.1023/A:1006468713614 (Pubitemid 30237943)
28. Ashford D. A., Di Pietra J., Lingappa J., Woods C., Noll H., Neville B., Weyant R., Bragg S. L., Spiegel R. A., Tappero J., Perkins B. A., Adverse events in humans associated with accidental exposure to the livestock brucellosis vaccine RB51. Vaccine 2004 22 25-26 3435 3439 2-s2.0-4143082695 10.1016/j.vaccine.2004.02.041 (Pubitemid 39089100)
29. Alton G. G., Elberg S. S., Rev 1 Brucella melitensis vaccine. Veterinary Bulletin 1967 37 793 800
30. Banai M., Control of small ruminant brucellosis by use of Brucella melitensis Rev.1 vaccine: laboratory aspects and field observations. Veterinary Microbiology 2002 90 1-4 497 519 2-s2.0-0037146616 10.1016/S0378-1135(02)00231-6 (Pubitemid 35279898)
31. Lord V. R., Cherwonogrodzky J. W., Schurig G. G., Lord R. D., Marcano M. J., Meléndez G. E., Venezuelan field trials of vaccines against brucellosis in swine. American Journal of Veterinary Research 1998 59 5 546 551 2-s2.0-0031832202 (Pubitemid 28267619)
32. WHO/MZCP, Human and Animal Brucellosis 1998 Damascus, Syria WHO
33. Minas A., Minas M., Stournara A., Tselepidis S., The "effects" of Rev-1 vaccination of sheep and goats on human brucellosis in Greece. Preventive Veterinary Medicine 2004 64 1 41 47 2-s2.0-3042802207 10.1016/j.prevetmed.2004.03.007 (Pubitemid 38847906)
34. Refai M., Incidence and control of brucellosis in the Near East region. Veterinary Microbiology 2002 90 1-4 81 110 2-s2.0-0037146666 10.1016/S0378-1135(02)00248-1 (Pubitemid 35279871)
35. Becker H. N., Belden R. C., Breault T., Brucellosis in feral swine in Florida. Journal of the American Veterinary Medical Association 1978 173 9 1181 1182 2-s2.0-0018070590 (Pubitemid 9050144)
36. Godfroid J., Käsbohrer A., Brucellosis in the European Union and Norway at the turn of the twenty-first century. Veterinary Microbiology 2002 90 1-4 135 145 10.1016/S0378-1135(02)00217-1 (Pubitemid 35279873)
37. da Costa Martins R., Irache J. M., Gamazo C., Acellular vaccines for ovine brucellosis: a safer alternative against a worldwide disease. Expert Review of Vaccines 2012 11 1 87 95 10.1586/erv.11.172
38. Arsenault J., Girard C., Dubreuil P., Bélanger D., Lack of evidence of Brucella ovis infection in rams in Quebec. The Canadian Veterinary Journal 2004 45 4 312 313 2-s2.0-2442602374 (Pubitemid 38618675)
39. Perkins S. D., Smither S. J., Atkins H. S., Towards a Brucella vaccine for humans. FEMS Microbiology Reviews 2010 34 3 379 394 2-s2.0-77950380555 10.1111/j.1574-6976.2010.00211.x
40. Pasquevich K. A., Ibañez A. E., Coria L. M., Samartino C. G., Estein S. M., Zwerdling A., Barrionuevo P., Oliveira F. S., Seither C., Warzecha H., Oliveira S. C., Giambartolomei G. H., Cassataro J., An oral vaccine based on U-Omp19 induces protection against B. abortus mucosal challenge by inducing an adaptive IL-17 immune response in mice. PLoS ONE 2011 6 1, article e16203 2-s2.0-79251592270 10.1371/journal.pone.0016203
41. Fugier E., Pappas G., Gorvel J. P., Virulence factors in brucellosis: implications for aetiopathogenesis and treatment. Expert Reviews in Molecular Medicine 2007 9 35 1 10 2-s2.0-38449119589 10.1017/S1462399407000543 (Pubitemid 351552427)
42. Pasquevich K. A., Samartino C. G., Coria L. M., Estein S. M., Zwerdling A., Ibañez A. E., Barrionuevo P., de Oliveira F. S., Carvalho N. B., Borkowski J., Oliveira S. C., Warzecha H., Giambartolomei G. H., Cassataro J., The protein moiety of Brucella abortus outer membrane protein 16 is a new bacterial pathogen-associated molecular pattern that activates dendritic cells in vivo, induces a Th1 immune response, and is a promising self-adjuvanting vaccine against systemic and oral acquired brucellosis. Journal of Immunology 2010 184 9 5200 5212 2-s2.0-77954477951 10.4049/jimmunol.0902209
43. Ruecker C., Guzmán C. A., Vaccines: from empirical development to rational desing. PLOS Pathogens 2012 8 11 e1003001
44. Delvecchio V. G., Alefantis T., Ugalde R. A., Comerci D., Marchesini M. I., Khan A., Lubitz W., Mujer C. V., Identification of protein candidates for developing bacterial ghost vaccines against Brucella. Methods of Biochemical Analysis 2006 49 363 377 2-s2.0-33749064150 (Pubitemid 44621321)
45. Cassataro J., Estein S. M., Pasquevich K. A., Velikovsky C. A., de La Barrera S., Bowden R., Fossati C. A., Giambartolomei G. H., Vaccination with the recombinant Brucella outer membrane protein 31 or a derived 27-amino-acid synthetic peptide elicits a CD4+ T helper 1 response that protects against Brucella melitensis infection. Infection and Immunity 2005 73 12 8079 8088 2-s2.0-28444434119 10.1128/IAI.73.12.8079-8088.2005 (Pubitemid 41740295)
46. Edmonds M. D., Cloeckaert A., Elzer P. H., Brucella species lacking the major outer membrane protein Omp25 are attenuated in mice and protect against Brucella melitensis and Brucella ovis. Veterinary Microbiology 2002 88 3 205 221 2-s2.0-0037009220 10.1016/S0378-1135(02)00110-4 (Pubitemid 34876574)
47. Goel D., Bhatnagar R., Intradermal immunization with outer membrane protein 25 protects Balb/c mice from virulent B. abortus 544. Molecular Immunology 2012 51 2 159 168 10.1016/j.molimm.2012.02.126
48. Delpino M. V., Estein S. M., Fossati C. A., Baldi P. C., Cassataro J., Vaccination with Brucella recombinant DnaK and SurA proteins induces protection against Brucella abortus infection in BALB/c mice. Vaccine 2007 25 37-38 6721 6729 2-s2.0-34548321638 10.1016/j.vaccine.2007.07.002 (Pubitemid 47342467)
49. Cassataro J., Pasquevich K. A., Estein S. M., Laplagne D. A., Velikovsky C. A., de la Barrera S., Bowden R., Fossati C. A., Giambartolomei G. H., Goldbaum F. A., A recombinant subunit vaccine based on the insertion of 27 amino acids from Omp31 to the N-terminus of BLS induced a similar degree of protection against B. ovis than Rev.1 vaccination. Vaccine 2007 25 22 4437 4446 2-s2.0-34247872947 10.1016/j.vaccine.2007.03.028 (Pubitemid 46695804)
50. Al-Mariri A., Tibor A., Mertens P., de Bolle X., Michel P., Godefroid J., Walravens K., Letesson J. J., Protection of BALB/c mice against Brucella abortus 544 challenge by vaccination with bacterioferritin or P39 recombinant proteins with CpG oligodeoxynucleotides as adjuvant. Infection and Immunity 2001 69 8 4816 4822 2-s2.0-0034927083 10.1128/IAI.69.8.4816-4822.2001 (Pubitemid 32674460)
51. Kaushik P., Singh D. K., Kumar S. V., Tiwari A. K., Shukla G., Dayal S., Chaudhuri P., Protection of mice against Brucella abortus 544 challenge by vaccination with recombinant OMP28 adjuvanted with CpG oligonucleotides. Veterinary Research Communications 2010 34 2 119 132 2-s2.0-77952550263 10.1007/s11259-009-9337-x
52. Gupta V. K., Radhakrishnan G., Harms J., Splitter G., Invasive Escherichia coli vaccines expressing Brucella melitensis outer membrane proteins 31 or 16 or periplasmic protein BP26 confer protection in mice challenged with B. melitensis. Vaccine 2012 30 27 4017 4022
53. Sáez D., Fernández P., Rivera A., Andrews E., Oñate A., Oral immunization of mice with recombinant Lactococcus lactis expressing Cu, Zn superoxide dismutase of Brucella abortus triggers protective immunity. Vaccine 2012 30 7 1283 1290 10.1016/j.vaccine.2011.12.088
54. Oñate A. A., Donoso G., Moraga-Cid G., Folch H., Céspedes S., Andrews E., An RNA vaccine based on recombinant Semliki Forest virus particles expressing the Cu,Zn superoxide dismutase protein of Brucella abortus induces protective immunity in BALB/c mice. Infection and Immunity 2005 73 6 3294 3300 2-s2.0-19744374114 10.1128/IAI.73.6.3294-3300.2005 (Pubitemid 40745869)
55. Baloglu S., Boyle S. M., Vemulapalli R., Sriranganathan N., Schurig G. G., Toth T. E., Immune responses of mice to vaccinia virus recombinants expressing either Listeria monocytogenes partial listeriolysin or Brucella abortus ribosomal L7/L12 protein. Veterinary Microbiology 2005 109 1-2 11 17 2-s2.0-21744455459 10.1016/j.vetmic.2005.04.011 (Pubitemid 40943340)
56. Cassataro J., Velikovsky C. A., de La Barrera S., Estein S. M., Bruno L., Bowden R., Pasquevich K. A., Fossati C. A., Giambartolomei G. H., A DNA vaccine coding for the Brucella outer membrane protein 31 confers protection against B. melitensis and B. ovis infection by eliciting a specific cytotoxic response. Infection and Immunity 2005 73 10 6537 6546 2-s2.0-25444524000 10.1128/IAI.73.10.6537-6546.2005 (Pubitemid 41368818)
57. Velikovsky C. A., Cassataro J., Giambartolomei G. H., Goldbaum F. A., Estein S., Bowden R. A., Bruno L., Fossati C. A., Spitz M., A DNA vaccine encoding lumazine synthase from Brucella abortus induces protective immunity in BALB/c mice. Infection and Immunity 2002 70 5 2507 2511 2-s2.0-0036121919 10.1128/IAI.70.5.2507-2511.2002 (Pubitemid 34408394)
58. Luo D., Ni B., Li P., Shi W., Zhang S., Han Y., Mao L., He Y., Wu Y., Wang X., Protective immunity elicited by a divalent DNA vaccine encoding both the L7/L12 and Omp16 genes of Brucella abortus in BALB/c mice. Infection and Immunity 2006 74 5 2734 2741 2-s2.0-33646359172 10.1128/IAI.74.5.2734-2741.2006 (Pubitemid 43672982)
59. Luo D. Y., Li P., Xing L., Zhao G. Y., Shi W., Zhang S. L., Wang X. L., DNA vaccine encoding L7/L12-P39 of Brucella abortus induces protective immunity in BALB/c mice. Chinese Medical Journal 2006 119 4 331 334 2-s2.0-33645292375 (Pubitemid 47034004)
60. Yu D. H., Li M., Hu X. D., Cai H., A combined DNA vaccine enhances protective immunity against Mycobacterium tuberculosis and Brucella abortus in the presence of an IL-12 expression vector. Vaccine 2007 25 37-38 6744 6754 2-s2.0-34548292484 10.1016/j.vaccine.2007.06.061 (Pubitemid 47332727)
61. González-Smith A., Vemulapalli R., Andrews E., Oñate A., Evaluation of Brucella abortus DNA vaccine by expression of Cu-Zn superoxide dismutase antigen fused to IL-2. Immunobiology 2006 211 1-2 65 74 2-s2.0-31544432038 10.1016/j.imbio.2005.09.004 (Pubitemid 43153701)
62. Singha H., Mallick A. I., Jana C., Isore D. P., Goswami T. K., Srivastava S. K., Azevedo V. A., Chaudhuri P., Owais M., Escheriosomes entrapped DNA vaccine co-expressing Cu-Zn superoxide dismutase and IL-18 confers protection against Brucella abortus. Microbes and Infection 2008 10 10-11 1089 1096 2-s2.0-54049123216 10.1016/j.micinf.2008.05.007
63. Hu X. D., Chen S. T., Li J. Y., Yu D. H., Yi-zhang, Cai H., An IL-15 adjuvant enhances the efficacy of a combined DNA vaccine against Brucella by increasing the CD8+ cytotoxic T cell response. Vaccine 2010 28 12 2408 2415 2-s2.0-77249178689 10.1016/j.vaccine.2009.12.076
64. Yu D. H., Hu X. D., Cai H., A combined DNA vaccine encoding BCSP31, SOD, and L7/L12 confers high protection against Brucella abortus 2308 by inducing specific CTL responses. DNA and Cell Biology 2007 26 6 435 443 2-s2.0-34250792187 10.1089/dna.2006.0552 (Pubitemid 46981698)
65. Amano A., Takeuchi H., Furuta N., Outer membrane vesicles function as offensive weapons in host-parasite interactions. Microbes and Infection 2010 12 11 791 798 2-s2.0-77957752025 10.1016/j.micinf.2010.05.008
66. Beveridge T. J., Structures of gram-negative cell walls and their derived membrane vesicles. Journal of Bacteriology 1999 181 16 4725 4733 2-s2.0-0032839616 (Pubitemid 29383496)
67. Ellis T. N., Kuehn M. J., Virulence and immunomodulatory roles of bacterial outer membrane vesicles. Microbiology and Molecular Biology Reviews 2010 74 1 81 94 2-s2.0-77749309281 10.1128/MMBR.00031-09
68. Kuehn M. J., Kesty N. C., Bacterial outer membrane vesicles and the host-pathogen interaction. Genes and Development 2005 19 22 2645 2655 2-s2.0-27744480818 10.1101/gad.1299905 (Pubitemid 41627932)
69. Mashburn-Warren L. M., Whiteley M., Special delivery: vesicle trafficking in prokaryotes. Molecular Microbiology 2006 61 4 839 846 2-s2.0-33746561249 10.1111/j.1365-2958.2006.05272.x (Pubitemid 44134164)
70. Unal C. M., Schaar V., Riesbeck K., Bacterial outer membrane vesicles in disease and preventive medicine. Seminars in Immunopathology 2011 33 5 395 408 10.1007/s00281-010-0231-y
71. Boigegrain R. A., Salhi I., Alvarez-Martinez M. T., Machold J., Fedon Y., Arpagaus M., Weise C., Rittig M., Rouot B., Release of periplasmic proteins of Brucella suis upon acidic shock involves the outer membrane protein Omp25. Infection and Immunity 2004 72 10 5693 5703 2-s2.0-4644359498 10.1128/IAI.72.10.5693-5703.2004 (Pubitemid 39303679)
72. Gamazo C., Winter A. J., Moriyon I., Riezu-Boj J. I., Blasco J. M., Diaz R., Comparative analyses of proteins extracted by hot saline or released spontaneously into outer membrane blebs from field strains of Brucella ovis and Brucella melitensis. Infection and Immunity 1989 57 5 1419 1426 2-s2.0-0024517697 (Pubitemid 19114158)
73. Avila-Calderón E. D., Lopez-Merino A., Jain N., Characterization of outer membrane vesicles from Brucella melitensis and protection induced in mice. Clinical and Developmental Immunology 2012 2012 352493 10.1155/2012/352493
74. Jain-Gupta N., Contreras-Rodriguez A., Vemulapalli R., Pluronic P85 enhances the efficacy of outer membrane vesicles as a subunit vaccine against Brucella melitensis challenge in mice. FEMS Immunology and Medical Microbiology 2012 66 3 436 444 10.1111/1574-695X.12010
75. Pollak C. N., Delpino M. V., Fossati C. A., Baldi P. C., Outer membrane vesicles from Brucella abortus promote bacterial internalization by human monocytes and modulate their innate immune response. PLoS One 2012 7 11 e50214