title: Aging promotes B-1b cell responses to native, but not protein-conjugated, pneumococcal polysaccharides: implications for vaccine protection in older adults.
abstract: The efficacy of different vaccines in protecting elderly individuals against Streptococcus pneumoniae infections is not clear. In the current study, aged mice (22-25 months old) exhibited significantly increased susceptibility to respiratory infection with serotype 3 S. pneumoniae relative to younger adult mice, regardless of whether mice were naive or immunized with native pneumococcal polysaccharide (PPS; Pneumovax23) or protein-PPS conjugate (Prevnar-13) vaccines. Nonetheless, Pneumovax-immunized aged mice developed limited bacteremia following respiratory challenge and exhibited significantly increased survival following systemic challenge relative to Prevnar-immune aged mice and young mice that had received either vaccine. This was explained by >10-fold increases in PPS-specific immunoglobulin G (IgG) levels in Pneumovax-immunized aged mice relative to other groups. Remarkably, PPS3-specific B-cell expansion, IgG switching, plasmablast differentiation, and spleen and bone marrow antibody-secreting cell frequencies were 10-fold higher in aged mice following Pneumovax immunization relative to young mice, due to significantly increased B-1b cell participation. In summary, this study highlights (1) the need to devise strategies to enhance respiratory immunity in aged populations, (2) the diverse responses young and aged populations generate to Pneumovax vs Prevnar vaccines, and (3) the potential value of exploiting B-1b cell responses in aged individuals for increased vaccine efficacy.
authors: Department of Microbiology and Immunology.
authors: Karen M
authors: KM
authors: Haas
authors: Maria W
authors: MW
authors: Blevins
authors: Kevin P
authors: KP
authors: High
authors: Bing
authors: B
authors: Pang
authors: W Edward
authors: WE
authors: Swords
authors: Rama D
authors: RD
authors: Yammani
mesh_terms: D000367:Age Factors; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D004198:Disease Susceptibility / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D022242:Pneumococcal Vaccines / Q000276:immunology* / Q000494:pharmacology; D011018:Pneumonia, Pneumococcal / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology
chemical_list: C538862:13-valent pneumococcal vaccine; C414006:23-valent pneumococcal capsular polysaccharide vaccine; D000907:Antibodies, Bacterial; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial
keywords: B-1b cells; Pneumovax23; Prevnar-13; Streptococcus pneumoniae; aging; humoral immunity; vaccines
references: J Immunol. 2004 Jun 15;172(12):7603-9
references: 15187140
references: Vaccine. 2001 Nov 12;20(3-4):545-53
references: 11672921
references: J Allergy Clin Immunol. 2012 Jul;130(1):272-5
references: 22664161
references: Aging Dis. 2012 Feb;3(1):51-67
references: 22500271
references: J Immunol. 2012 Jul 15;189(2):575-86
references: 22706079
references: Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5382-7
references: 22421134
references: J Infect Dis. 2009 Aug 15;200(4):546-54
references: 19586419
references: J Immunol. 2013 Apr 1;190(7):3100-8
references: 23455507
references: Curr Top Microbiol Immunol. 2008;319:105-30
references: 18080416
references: Immunol Rev. 2000 Jun;175:70-9
references: 10933592
references: Infect Immun. 2006 Apr;74(4):2177-86
references: 16552048
references: J Immunol. 2007 Dec 1;179(11):7523-34
references: 18025197
references: J Infect Dis. 1992 Jun;165 Suppl 1:S44-8
references: 1588176
references: J Infect Dis. 2003 Aug 1;188(3):339-48
references: 12870114
references: Aging Cell. 2011 Oct;10(5):798-806
references: 21615674
references: J Infect Dis. 1996 Apr;173(4):1014-8
references: 8603942
references: J Infect Dis. 1996 Nov;174(5):994-1000
references: 8896500
references: Nat Rev Immunol. 2011 Jan;11(1):34-46
references: 21151033
references: Immunity. 2005 Jul;23(1):7-18
references: 16039575
references: J Immunol. 2009 Sep 15;183(6):3661-71
references: 19710450
references: Aging Cell. 2009 Jun;8(3):277-87
references: 19627267
references: Semin Immunol. 2012 Oct;24(5):342-9
references: 22560930
references: Expert Rev Vaccines. 2008 May;7(4):467-79
references: 18444893
references: Clin Infect Dis. 2009 Nov 1;49(9):1318-25
references: 19814624
references: Drugs Aging. 2007;24(10):791-800
references: 17896829
references: Infect Immun. 2011 Jan;79(1):314-20
references: 21041499
references: J Immunol. 2011 Nov 15;187(10):5183-95
references: 22003198
references: FASEB J. 2008 Mar;22(3):659-61
references: 17942826
references: Clin Infect Dis. 2011 Mar 1;52(5):633-40
references: 21292668
references: Infect Immun. 2005 Nov;73(11):7465-76
references: 16239548
references: Aging Dis. 2011 Dec;2(6):487-500
references: 22288022
references: Annu Rev Immunol. 1995;13:655-92
references: 7612238
references: Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5905-10
references: 16585532
references: Immunity. 2002 Dec;17(6):713-23
references: 12479818
references: J Exp Med. 2006 Oct 30;203(11):2541-50
references: 17060475
references: Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4542-6
references: 17360560
references: Infect Immun. 1997 Jan;65(1):242-7
references: 8975918
references: J Immunol. 2011 Feb 15;186(4):2454-61
references: 21242514
references: Clin Immunol. 2010 Jun;135(3):501-2
references: 20207588
references: Vaccine. 2008 Oct 9;26(43):5521-6
references: 18706464
references: J Infect Dis. 2003 Mar 15;187(6):1000-9
references: 12660947
references: Semin Immunol. 2012 Oct;24(5):373-82
references: 22633440
references: J Am Geriatr Soc. 2010 Apr;58(4):765-76
references: 20398161
references: J Immunol. 2009 Nov 15;183(10):6359-68
references: 19841173
references: Vaccine. 2006 Nov 30;24(49-50):7197-203
references: 16860443