Epitope mapping immunodominant regions of the PilA protein of nontypeable Haemophilus influenzae (NTHI) to facilitate the design of two novel chimeric vaccine candidates.
We designed and tested three PilA-derived vaccine candidates in a chinchilla model of ascending nontypeable Haemophilus influenzae (NTHI)-induced otitis media (OM). Delivery of antiserum directed against each immunogen conferred varying degrees of protection. Presentation of a B-cell epitope derived from the OMP P5 adhesin at the N-terminus of recombinant soluble PilA protein (as opposed to the C-terminus), resulted in a protective chimeric immunogen that combined epitopes from two distinct NTHI adhesins (type IV pili and OMP P5). Incorporating protective epitopes derived from two NTHI adhesins/virulence determinants into a single pediatric vaccine candidate to prevent OM has multiple potential inherent advantages.
Novotny
Laura A
LA
The Research Institute at Nationwide Children's Hospital, Center for Microbial Pathogenesis and The Ohio State University College of Medicine, 700 Children's Drive, W591, Columbus, OH 43205, United States.
Adams
Leanne D
LD
Kang
D Richard
DR
Wiet
Gregory J
GJ
Cai
Xueya
X
Sethi
Sanjay
S
Murphy
Timothy F
TF
Bakaletz
Lauren O
LO
D018829:Adhesins, Bacterial / Q000276:immunology*; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology*; D015374:Biosensing Techniques; D002675:Child, Preschool; D002682:Chinchilla; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D006192:Haemophilus Infections / Q000276:immunology / Q000517:prevention & control*; D006193:Haemophilus influenzae / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007223:Infant; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010034:Otitis Media with Effusion / Q000276:immunology / Q000517:prevention & control*; D017434:Protein Structure, Tertiary; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology
D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D018985:Epitopes, B-Lymphocyte; D016056:Immunodominant Epitopes
J Infect Dis. 1997 Jun;175(6):1440-5
9180184
Infect Immun. 2000 Apr;68(4):2119-28
10722609
Infect Immun. 1999 Jun;67(6):2746-62
10338477
J Pediatr. 1993 Feb;122(2):212-8
8429433
Cell Microbiol. 2002 Apr;4(4):191-200
11952636
Infect Immun. 2003 Aug;71(8):4691-9
12874350
Infect Immun. 2007 Dec;75(12):5559-64
17908808
Eur J Pediatr. 2001 Jul;160(7):407-13
11475577
N Engl J Med. 2002 Aug 15;347(7):465-71
12181400
Infect Immun. 2005 Mar;73(3):1635-43
15731063
Prog Allergy. 1983;33:314-31
6187017
Curr Opin Infect Dis. 2003 Apr;16(2):129-34
12734445
Vaccine. 1997 Jun;15(9):955-61
9261941
Infect Immun. 2001 Jan;69(1):602-6
11119562
Ann Otol Rhinol Laryngol. 1982 Jan-Feb;91(1 Pt 1):20-4
7073172
Infect Immun. 1994 May;62(5):1710-8
8168932
Science. 1998 Jun 26;280(5372):2114-8
9641917
Ann Otol Rhinol Laryngol Suppl. 1994 May;163:34-8
8179267
Cell Microbiol. 2009 Sep;11(9):1399-408
19500108
J Bacteriol. 2007 May;189(10):3868-75
17322318
Mol Microbiol. 1999 Jun;32(6):1316-32
10383771
Mol Microbiol. 2007 Sep;65(5):1288-99
17645732
Pediatr Infect Dis J. 1990 Sep;9(9):623-6
2122410
Scand J Infect Dis. 2003;35(9):608-13
14620143
Am J Respir Crit Care Med. 2004 Feb 15;169(4):448-53
14597486
J Infect Dis. 1995 Jul;172(1):132-5
7797903
J Immunol. 2003 Aug 15;171(4):1978-83
12902501
Infect Immun. 1999 Jan;67(1):187-92
9864214
Infect Immun. 2000 May;68(5):2756-65
10768970
J Bacteriol. 2005 Jul;187(13):4627-36
15968074
J Infect Dis. 1993 Oct;168(4):865-72
8397268
J Mol Biol. 2007 Nov 23;374(2):426-42
17936788
Nat Rev Microbiol. 2004 Jul;2(7):552-68
15197391
Vaccine. 2001 Mar 21;19(17-19):2323-8
11257356
Vaccine. 2006 May 29;24(22):4804-11
16616975
Infect Immun. 2003 Jun;71(6):3454-62
12761130
Vaccine. 1991 Mar;9(3):154-62
1675029
Infect Immun. 2004 Nov;72(11):6262-70
15501752
Microb Pathog. 1997 Aug;23(2):119-26
9245624
Acta Otolaryngol. 1993 Jan;113(1):88-92
8442428
Vaccine. 2002 Oct 4;20(29-30):3590-7
12297406
Ann Otol Rhinol Laryngol. 1991 Aug;100(8):612-5
1908199
Infect Immun. 2007 Jun;75(6):3027-32
17403869
Infect Immun. 1994 May;62(5):2002-20
7909539