scholarly journals Outer Membrane Protein Profiles of Paired Nasopharyngeal and Middle Ear Isolates of Nontypable Haemophilus influenzae from Mexican Children with Acute Otitis Media

1999 ◽  
Vol 28 (2) ◽  
pp. 267-273 ◽  
Author(s):  
Alberto Villaseñor‐Sierra ◽  
José Ignacio Santos
Keyword(s):  
Membrane Protein ◽  
Haemophilus Influenzae ◽  
Outer Membrane ◽  
Otitis Media ◽  
Middle Ear ◽  
Outer Membrane Protein ◽  
Acute Otitis Media ◽  
Protein Profiles ◽  
Mexican Children

scholarly journals Variability of Outer Membrane Protein P1 and Its Evaluation as a Vaccine Candidate against Experimental Otitis Media due to Nontypeable Haemophilus influenzae: an Unambiguous, Multifaceted Approach

2000 ◽  
Vol 68 (8) ◽  
pp. 4505-4517 ◽  
Author(s):  
Gilles R. Bolduc ◽  
Valérie Bouchet ◽  
Ru-Zhang Jiang ◽  
Janet Geisselsoder ◽  
Que Chi Truong-Bolduc ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Haemophilus Influenzae ◽  
Outer Membrane ◽  
Otitis Media ◽  
Outer Membrane Protein ◽  
Natural Populations ◽  
Nontypeable Haemophilus Influenzae ◽  
Animal Testing ◽  
Knowing That ◽  
Efficacious Vaccine

ABSTRACT Candidate vaccine antigens for preventing otitis media caused by nontypeable Haemophilus influenzae (NTHI) should possess one or more conserved epitopes. We sought to evaluate the candidacy of P1, a surface-expressed outer membrane protein knowing that this antigen is subject to diversifying selection. Therefore, we selected NTHI strains from among >500 phylogenically variant isolates representative of the diversity found in natural populations ofH. influenzae. Twenty-three variants of P1 (≤95% similarity) were identified among 42 strains. When chinchillas were immunized with recombinant P1 (rP1) obtained from one of these isolates (BCH-3), all animals developed antibodies specific for rP1. Immunized animals were protected against disease when challenged with BCH-3, but not with an ompP1 mutant of BCH-3 or a strain (BCH-2) possessing a heterologous P1 (91% identity). We conclude that (i) while P1 induces protection against NTHI-mediated otitis media, development of a polyvalent vaccine reflecting the variability of P1 would be necessary to construct an efficacious vaccine and (ii) use of a phylogenically characterized collection of representative isolates in concert with gene sequencing, cloning, gene inactivation, and animal testing offers an efficient, rational, and rigorous strategy for evaluating the potential problems associated with variability of vaccine targets and specificity of related immune responses.

scholarly journals Efficacy of the 26-Kilodalton Outer Membrane Protein and Two P5 Fimbrin-Derived Immunogens To Induce Clearance of Nontypeable Haemophilus influenzae from the Rat Middle Ear and Lungs as Well as from the Chinchilla Middle Ear and Nasopharynx

2003 ◽  
Vol 71 (8) ◽  
pp. 4691-4699 ◽  
Author(s):  
Jennelle M. Kyd ◽  
Allan W. Cripps ◽  
Laura A. Novotny ◽  
Lauren O. Bakaletz
Keyword(s):  
Membrane Protein ◽  
Haemophilus Influenzae ◽  
Outer Membrane ◽  
Outcome Measures ◽  
Middle Ear ◽  
Outer Membrane Protein ◽  
Strong Support ◽  
Keyhole Limpet Hemocyanin ◽  
Nontypeable Haemophilus Influenzae ◽  
Host System

ABSTRACT The rat middle ear and lung clearance model has been used to show that the nontypeable Haemophilus influenzae 26-kDa outer membrane protein OMP26 is highly efficacious as a mucosal immunogen, inducing significantly enhanced clearance in immunized rats upon direct challenge of these two anatomic sites. Similarly, the chinchilla model of middle ear and nasopharyngeal clearance has been used to show that two P5 fimbrin adhesin-derived immunogens, LB1 and lipoprotein D (LPD)-LB1(f)2,1,3, are highly efficacious as parenteral immunogens. Both induced significantly augmented clearance of nontypeable H. influenzae upon challenge of these sites. Here, these three nontypeable H. influenzae immunogens in addition to six bovine serum albumin and keyhole limpet hemocyanin conjugates of the synthetic peptide LB1(f) were assayed for relative efficacy in the reciprocal rodent model system. OMP26 was assayed in the chinchilla host by a parenteral immunization route, with clearance of the middle ear and nasopharynx used as outcome measures. Both LB1 and LPD-LB1(f)2,1,3 were assayed in the rat host with a mucosal immunization route and clearance of nontypeable H. influenzae from the lungs and middle ears as outcome measures. Both of the immunogens were found to induce a high-titered and specific immune responses in the heterologous host system. Moreover, each was found to be highly efficacious in the reciprocal host system, providing strong support for the continued development and inclusion of both OMP26 and P5 fimbrin-derived peptides as candidate vaccine antigens directed at otitis media caused by nontypeable H. influenzae.

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