Relationship between surface accessibility for PpmA, PsaA, and PspA and antibody-mediated immunity to systemic infection by Streptococcus pneumoniae.
Antibodies to capsular polysaccharide (PS) are protective against systemic infection by Streptococcus pneumoniae, but the large number of pneumococcal serogroups and the age-related immunogenicity of pure PS limit the utility of PS-based vaccines. In contrast, cell wall-associated proteins from different capsular serotypes can be cross-reactive and immunogenic in all age groups. Therefore, we evaluated three pneumococcal proteins with respect to relative accessibility to antibody, in the context of intact pneumococci, and their ability to elicit protection against systemic infection by encapsulated S. pneumoniae. Sequences encoding pneumococcal surface adhesin A (PsaA), putative protease maturation protein A (PpmA), and the N-terminal region of pneumococcal surface protein A (PspA) from S. pneumoniae strain A66.1 were cloned and expressed in Escherichia coli. The presence of genes encoding PsaA, PpmA, and PspA in 11 clinical isolates was examined by PCR, and the expression of these proteins by each strain was examined by Western blotting with antisera raised to the respective recombinant proteins. We used flow cytometry to demonstrate that PspA was readily detectable on the surface of the pneumococcal strains analyzed, whereas PsaA and PpmA were not. Consistent with these observations, mice with passively or actively acquired antibodies to PspA or type 3 PS were equivalently protected from homologous systemic challenge with type 3 pneumococci, whereas mice with passively or actively acquired antibodies to PsaA or PpmA were not effectively protected. These experiments support the hypothesis that the extent of protection against systemic pneumococcal infection is influenced by target antigen accessibility to circulating host antibodies.
Gor
Dennis O
DO
Institute of Pathology, Case Western Reserve University, Cleveland, OH, USA. dgor@bu.edu
Ding
Xuedong
X
Briles
David E
DE
Jacobs
Michael R
MR
Greenspan
Neil S
NS
D018829:Adhesins, Bacterial; D000818:Animals; D000907:Antibodies, Bacterial / Q000008:administration & dosage / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D007114:Immunization; D007116:Immunization, Passive; D008074:Lipoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000378:metabolism / Q000472:pathogenicity
D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D008074:Lipoproteins; D026901:Membrane Transport Proteins; D022242:Pneumococcal Vaccines; C085000:PsaA protein, Streptococcus; D011994:Recombinant Proteins; C051592:pneumococcal surface protein A
Science. 2001 Jul 20;293(5529):498-506
11463916
Clin Infect Dis. 2001 Nov 1;33(9):1489-94
11588694
Infect Immun. 2000 Feb;68(2):796-800
10639448
Pediatr Infect Dis J. 2002 Sep;21(9):810-5
12352800
Infect Immun. 2003 Mar;71(3):1033-41
12595413
J Bacteriol. 1992 Jan;174(2):610-8
1729250
Clin Infect Dis. 2000 Jan;30(1):100-21
10619740
Pediatr Infect Dis J. 2000 Apr;19(4):394-7
10783042
Clin Diagn Lab Immunol. 2003 Mar;10(2):246-51
12626450
Infect Immun. 2000 Jul;68(7):4180-8
10858235
Infect Immun. 2000 Oct;68(10):5889-900
10992499
J Infect Dis. 1996 Feb;173(2):380-6
8568299
J Exp Med. 1944 Feb 1;79(2):137-58
19871359
Isr J Med Sci. 1987 Mar;23(3):174-80
3583698
Clin Infect Dis. 1995 Aug;21(2):345-51
8562743
Infect Immun. 1990 Oct;58(10):3293-9
1698178
Infect Immun. 1999 Dec;67(12):6533-42
10569772
Microb Pathog. 1990 Jan;8(1):61-9
2333033
N Engl J Med. 2003 May 1;348(18):1737-46
12724479
Infect Immun. 1999 Sep;67(9):4720-4
10456922
Emerg Infect Dis. 2001 Sep-Oct;7(5):832-6
11747695
Infect Immun. 1998 Oct;66(10):4748-54
9746574
J Immunol. 2002 Feb 15;168(4):1886-94
11823523
Infect Immun. 1998 Apr;66(4):1513-20
9529075
Vaccine. 2000 Dec 8;19 Suppl 1:S78-82
11163468
Infect Immun. 1999 Sep;67(9):4862-9
10456942
Infect Immun. 2000 May;68(5):3028-33
10769009
J Infect Dis. 2000 Dec;182(6):1694-701
11069242
Infect Immun. 1992 Jan;60(1):111-6
1729176
Scand J Infect Dis Suppl. 1994;93:55-62
8047858
N Engl J Med. 2001 Feb 8;344(6):403-9
11172176
J Infect Dis. 1983 Jul;148(1):131-7
6886479
Vaccine. 2000 Feb 25;18(16):1707-11
10689153
J Infect Dis. 2002 Feb 15;185(4):489-96
11865401
Lancet. 1997 Jul 26;350(9073):233-4
9242797
J Immunol. 2002 Apr 1;168(7):3437-43
11907102
J Infect Dis. 1983 Dec;148(6):1136-59
6361173
Epidemiol Infect. 2004 Apr;132(2):177-84
15061491
Vaccine. 2000 Mar 6;18(17):1811-21
10699329
J Med Microbiol. 2002 Feb;51(2):98-104
11863272
J Bacteriol. 2001 Oct;183(19):5709-17
11544234
Infect Immun. 1998 Aug;66(8):3744-51
9673257
Infect Immun. 2001 Oct;69(10):5997-6003
11553536
Infect Immun. 2003 Aug;71(8):4498-505
12874329
Microb Pathog. 1992 Nov;13(5):343-55
1297913
Infect Immun. 2002 Oct;70(10):5589-95
12228286
Microbiol Mol Biol Rev. 2001 Jun;65(2):187-207 ; first page, table of contents
11381099
Infect Immun. 2001 Feb;69(2):949-58
11159990
Infect Immun. 2004 Jan;72(1):114-22
14688088
Infect Immun. 2001 Mar;69(3):1593-8
11179332
Cell. 1993 Mar 26;72(6):823-6
8458078
Annu Rev Immunol. 1984;2:461-91
6399850
Infect Immun. 1997 May;65(5):1967-71
9125591