Relative immunogenicity and efficacy of two synthetic chimeric peptides of fimbrin as vaccinogens against nasopharyngeal colonization by nontypeable Haemophilus influenzae in the chinchilla

Vaccine ◽  
1997 ◽  
Vol 15 (9) ◽  
pp. 955-961 ◽  
Author(s):  
Lauren O. Bakaletz ◽  
Edward R. Leake ◽  
John M. Billy ◽  
Pravin T.P. Kaumaya
Keyword(s):  
Haemophilus Influenzae ◽  
Nontypeable Haemophilus Influenzae ◽  
Nasopharyngeal Colonization ◽  
Chimeric Peptides

Epidemiology of Nasopharyngeal Colonization with Nontypeable Haemophilus influenzae in the First 2 Years of Life

1995 ◽  
Vol 172 (1) ◽  
pp. 132-135 ◽  
Author(s):  
H. Faden ◽  
L. Duffy ◽  
A. Williams ◽  
D. A. Krystofik ◽  
J. Wolf ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Nontypeable Haemophilus Influenzae ◽  
Nasopharyngeal Colonization

scholarly journals Analysis of Nontypeable Haemophilus influenzae Phase-Variable Genes During Experimental Human Nasopharyngeal Colonization

2013 ◽  
Vol 208 (5) ◽  
pp. 720-727 ◽  
Author(s):  
Jessica Poole ◽  
Eric Foster ◽  
Kathryn Chaloner ◽  
Jason Hunt ◽  
Michael P. Jennings ◽  
...  
Keyword(s):  
Haemophilus Influenzae ◽  
Phase Variable ◽  
Nontypeable Haemophilus Influenzae ◽  
Nasopharyngeal Colonization ◽  
Variable Genes

scholarly journals Multiple Consecutive Lavage Samplings Reveal Greater Burden of Disease and Provide Direct Access to the Nontypeable Haemophilus influenzae Biofilm in Experimental Otitis Media

2007 ◽  
Vol 75 (8) ◽  
pp. 4158-4172 ◽  
Author(s):  
Magali Leroy ◽  
Howard Cabral ◽  
Marisol Figueira ◽  
Valérie Bouchet ◽  
Heather Huot ◽  
...  
Keyword(s):  
Gene Expression ◽  
Haemophilus Influenzae ◽  
Otitis Media ◽  
Vaccine Development ◽  
Ex Vivo ◽  
Direct Analysis ◽  
Direct Access ◽  
Nontypeable Haemophilus Influenzae ◽  
Nasopharyngeal Colonization

ABSTRACT The typically recovered quantity of nontypeable Haemophilus influenzae (NTHi) bacteria in an ex vivo middle ear (ME) aspirate from the chinchilla model of experimental otitis media is insufficient for direct analysis of gene expression by microarray or of lipopolysaccharide glycoforms by mass spectrometry. This prompted us to investigate a strategy of multiple consecutive lavage samplings to increase ex vivo bacterial recovery. As multiple consecutive lavage samples significantly increased the total number of bacterial CFU collected during nasopharyngeal colonization or ME infection, this led us to evaluate whether bacteria sequentially acquired from consecutive lavages were similar. Comparative observation of complete ex vivo sample series by microscopy initially revealed ME inflammatory fluid consisting solely of planktonic-phase NTHi. In contrast, subsequent lavage samplings of the same infected ear revealed the existence of bacteria in two additional growth states, filamentous and biofilm encased. Gene expression analysis of such ex vivo samples was in accord with different bacterial growth phases in sequential lavage specimens. The existence of morphologically distinct NTHi subpopulations with varying levels of gene expression indicates that the pooling of specimens requires caution until methods for their separation are developed. This study based on multiple consecutive lavages is consistent with prior reports that NTHi forms a biofilm in vivo, describes the means to directly acquire ex vivo biofilm samples without sacrificing the animal, and has broad applicability for a study of mucosal infections. Moreover, this approach revealed that the actual burden of bacteria in experimental otitis media is significantly greater than was previously reported. Such findings may have direct implications for antibiotic treatment and vaccine development against NTHi.

scholarly journals The C-Terminal Fragment of the Internal 110-Kilodalton Passenger Domain of the Hap Protein of Nontypeable Haemophilus influenzae Is a Potential Vaccine Candidate

2004 ◽  
Vol 72 (12) ◽  
pp. 6961-6968 ◽  
Author(s):  
Dai-Fang Liu ◽  
Kathryn W. Mason ◽  
Maria Mastri ◽  
Mehran Pazirandeh ◽  
David Cutter ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Haemophilus Influenzae ◽  
Recombinant Proteins ◽  
Terminal Region ◽  
Vaccine Antigen ◽  
Nontypeable Haemophilus Influenzae ◽  
Passenger Domain ◽  
Nasopharyngeal Colonization ◽  
Bacterial Aggregation ◽  
Potential Vaccine

ABSTRACT Nontypeable Haemophilus influenzae is a major causative agent of bacterial otitis media in children. H. influenzae Hap autotransporter protein is an adhesin composed of an outer membrane Hapβ region and a moiety of an extracellular internal 110-kDa passenger domain called HapS. The HapS moiety promotes adherence to human epithelial cells and extracellular matrix proteins, and it also mediates bacterial aggregation and microcolony formation. A recent work (D. L. Fink, A. Z. Buscher, B. A. Green, P. Fernsten, and J. W. St. Geme, Cell. Microbiol. 5:175-186, 2003) demonstrated that HapS adhesive activity resides within the C-terminal 311 amino acids (the cell binding domain) of the protein. In this study, we immunized mice subcutaneously with recombinant proteins corresponding to the C-terminal region of HapS from H. influenzae strains N187, P860295, and TN106 and examined the resulting immune response. Antisera against the recombinant proteins from all three strains not only recognized native HapS purified from strain P860295 but also inhibited H. influenzae Hap-mediated adherence to Chang epithelial cells. Furthermore, when mice immunized intranasally with recombinant protein plus mutant cholera toxin CT-E29H were challenged with strain TN106, they were protected against nasopharyngeal colonization. These observations demonstrate that the C-terminal region of HapS is capable of eliciting cross-reacting antibodies that reduce nasopharyngeal colonization, suggesting utility as a vaccine antigen for the prevention of nontypeable H. influenzae diseases.

scholarly journals Nasopharyngeal Colonization with Nontypeable Haemophilus influenzae in Chinchillas

1998 ◽  
Vol 66 (5) ◽  
pp. 1973-1980 ◽  
Author(s):  
Yan-ping Yang ◽  
Sheena M. Loosmore ◽  
Brian J. Underdown ◽  
Michel H. Klein
Keyword(s):  
Haemophilus Influenzae ◽  
Otitis Media ◽  
Middle Ear ◽  
Candidate Vaccine ◽  
Nontypeable Haemophilus Influenzae ◽  
Nasopharyngeal Colonization ◽  
Ear Infection ◽  
Middle Ear Infection ◽  
Significant Difference ◽  
Vaccine Antigens

ABSTRACT Colonization of the nasopharynx by a middle ear pathogen is the first step in the development of otitis media in humans. The establishment of an animal model of nasopharyngeal colonization would therefore be of great utility in assessing the potential protective ability of candidate vaccine antigens (especially adhesins) against otitis media. A chinchilla nasopharyngeal colonization model for nontypeable Haemophilus influenzae (NTHI) was developed with antibiotic-resistant strains. This model does not require coinfection with a virus. There was no significant difference in the efficiency of NTHI colonization between adult (1- to 2-year-old) and young (2- to 3-month-old) animals. However, the incidence of middle ear infection following nasopharyngeal colonization was significantly higher in young animals (83 to 89%) than in adult chinchillas (10 to 30%). Chinchillas that had recovered either from a previous middle ear infection caused by NTHI or from an infection by intranasal inoculation with NTHI were completely protected against nasopharyngeal colonization with a homologous strain and were found to be the best positive controls in protection studies. Systemic immunization of chinchillas with inactivated whole-cell preparations significantly protected animals not only against homologous NTHI colonization but also partially against heterologous NTHI infection. In all protected animals, significant serum anti-P6 and anti-HMW antibody responses were observed. The outer membrane P6 and high-molecular-weight (HMW) proteins appear to be promising candidate vaccine antigens to prevent nasopharyngeal colonization and middle ear infection caused by NTHI.

scholarly journals Immunization with HMW1 and HMW2 adhesins protects against colonization by heterologous strains of nontypeable Haemophilus influenzae

2021 ◽  
Vol 118 (32) ◽  
pp. e2019923118
Author(s):  
Nadia A. Kadry ◽  
Eric A. Porsch ◽  
Hao Shen ◽  
Joseph W. St. Geme
Keyword(s):  
Antibody Response ◽  
Respiratory Tract ◽  
Haemophilus Influenzae ◽  
Rhesus Macaques ◽  
Critical Role ◽  
Upper Respiratory Tract ◽  
Nontypeable Haemophilus Influenzae ◽  
Nasopharyngeal Colonization ◽  
Vaccine Potential ◽  
Tract Disease

Nontypeable Haemophilus influenzae (NTHi) is a common cause of localized respiratory tract disease and results in significant morbidity. The pathogenesis of NTHi disease begins with nasopharyngeal colonization, and therefore, the prevention of colonization represents a strategy to prevent disease. The NTHi HMW1 and HMW2 proteins are a family of conserved adhesins that are present in 75 to 80% of strains and have been demonstrated to play a critical role in colonization of the upper respiratory tract in rhesus macaques. In this study, we examined the vaccine potential of HMW1 and HMW2 using a mouse model of nasopharyngeal colonization. Immunization with HMW1 and HMW2 by either the subcutaneous or the intranasal route resulted in a strain-specific antibody response associated with agglutination of bacteria and restriction of bacterial adherence. Despite the specificity of the antibody response, immunization resulted in protection against colonization by both the parent NTHi strain and heterologous strains expressing distinct HMW1 and HMW2 proteins. Pretreatment with antibody against IL-17A eliminated protection against heterologous strains, indicating that heterologous protection is IL-17A dependent. This work demonstrates the vaccine potential of the HMW1 and HMW2 proteins and highlights the importance of IL-17A in protection against diverse NTHi strains.

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