title: Formalin-inactivated Coxiella burnetii phase I vaccine-induced protection depends on B cells to produce protective IgM and IgG.
abstract: To further understand the mechanisms of formalin-inactivated Coxiella burnetii phase I (PI) vaccine (PIV)-induced protection, we examined if B cell, T cell, CD4(+) T cell, or CD8(+) T cell deficiency in mice significantly affects the ability of PIV to confer protection against a C. burnetii infection. Interestingly, compared to wild-type (WT) mice, PIV conferred comparable levels of protection in CD4(+) T cell- or CD8(+) T cell-deficient mice and partial protection in T cell-deficient mice but did not provide measurable protection in B cell-deficient mice. These results suggest that PIV-induced protection depends on B cells. In addition, anti-PI-specific IgM was the major detectable antibody (Ab) in immune sera from PIV-vaccinated CD4(+) T cell-deficient mice, and passive transfer of immune sera from PIV-vaccinated CD4(+) T cell-deficient mice conferred significant protection. These results suggest that T cell-independent anti-PI-specific IgM may contribute to PIV-induced protection. Our results also suggested that PIV-induced protection may not depend on complement activation and Fc receptor-mediated effector functions. Furthermore, our results demonstrated that both IgM and IgG from PIV-vaccinated WT mouse sera were able to inhibit C. burnetii infection in vivo, but only IgM from PIV-vaccinated CD4(+) T cell-deficient mouse sera inhibited C. burnetii infection. Collectively, these findings suggest that PIV-induced protection depends on B cells to produce protective IgM and IgG and that T cell-independent anti-PI-specific IgM may play a critical role in PIV-induced protection against C. burnetii infection.
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Missouri-Columbia, Columbia, Missouri, USA. zhangguo@missouri.edu.
authors.forename: Guoquan
authors.initials: G
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.forename: Laura
authors.initials: L
authors.lastname: Schoenlaub
authors.forename: Alexandra
authors.initials: A
authors.lastname: Elliott
authors.forename: William
authors.initials: W
authors.lastname: Mitchell
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000378:metabolism; D000942:Antigens, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D016997:Coxiella burnetii / Q000187:drug effects / Q000276:immunology* / Q000472:pathogenicity; D005260:Female; D005557:Formaldehyde / Q000633:toxicity*; D007074:Immunoglobulin G / Q000378:metabolism*; D007075:Immunoglobulin M / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D011778:Q Fever / Q000517:prevention & control; D013047:Specific Pathogen-Free Organisms; D015164:Vaccines, Inactivated / Q000276:immunology; D014774:Virulence
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015164:Vaccines, Inactivated; D005557:Formaldehyde
references.citation: Infect Immun. 1977 Feb;15(2):601-7
references.pmid: 844906
references.citation: Am J Hyg. 1957 Sep;66(2):173-95
references.pmid: 13458182
references.citation: Infect Immun. 2008 May;76(5):2177-82
references.pmid: 18316379
references.citation: Microbiol Immunol. 1995;39(9):663-71
references.pmid: 8577279
references.citation: J Immunol. 2007 Dec 15;179(12):8372-80
references.pmid: 18056383
references.citation: Infect Immun. 1982 Mar;35(3):1091-102
references.pmid: 7068212
references.citation: Acta Virol. 1975 Sep;19(5):426-31
references.pmid: 241247
references.citation: Clin Microbiol Rev. 2003 Jan;16(1):65-78
references.pmid: 12525425
references.citation: PLoS One. 2012;7(1):e30841
references.pmid: 22303462
references.citation: J Immunol. 2002 Dec 1;169(11):6324-31
references.pmid: 12444139
references.citation: J Clin Microbiol. 2003 May;41(5):1869-74
references.pmid: 12734219
references.citation: Infect Immun. 1976 Oct;14(4):1087-96
references.pmid: 825466
references.citation: BMC Immunol. 2009 May 08;10:26
references.pmid: 19426498
references.citation: Can J Microbiol. 1956 May;2(3):310-21
references.pmid: 13316625
references.citation: Curr Protoc Immunol. 2008 Nov;Chapter 14:Unit 14.1
references.pmid: 19016445
references.citation: Infect Immun. 1981 Feb;31(2):641-5
references.pmid: 7216465
references.citation: Adv Immunol. 2006;91:1-44
references.pmid: 16938537
references.citation: Acta Virol. 1979 Jan;23(1):73-81
references.pmid: 35962
references.citation: J Immunol. 1976 Sep;117(3):996-1003
references.pmid: 986414
references.citation: Infect Immun. 2004 Nov;72(11):6191-6
references.pmid: 15501743
references.citation: Infect Immun. 2010 Jul;78(7):3019-26
references.pmid: 20351144
references.citation: Acta Virol. 1965 May;9:268-74
references.pmid: 14328226
references.citation: Methods Mol Biol. 2008;431:189-200
references.pmid: 18287757
references.citation: Vaccine. 2002 Jun 7;20(19-20):2623-34
references.pmid: 12057622
references.citation: Infect Immun. 2002 May;70(5):2519-25
references.pmid: 11953391
references.citation: Infect Immun. 2002 May;70(5):2598-604
references.pmid: 11953401
references.citation: Infect Immun. 1986 Mar;51(3):851-8
references.pmid: 3949384
references.citation: Infect Immun. 2007 Jul;75(7):3245-55
references.pmid: 17438029
references.citation: Med J Aust. 1994 Jun 6;160(11):704-8
references.pmid: 8202006
references.citation: Ann N Y Acad Sci. 2003 Jun;990:510-20
references.pmid: 12860683