Abstract

Nontypable Haemophilus influenzae (NTHi) is one of the major etiological agents of acute otitis media (AOM) which has very high morbidity among children in both developing and developed countries. The long term goal of this research is to better understand NTHi pathogenesis and human immune responses following nasopharyngeal (NP) colonization and AOM, in order to develop strategies for intervention in the disease. We will prospectively collect NP, middle ear fluids (MEF), and sera from young children age 2 to 24 months, who are otitis prone, have infrequent otitis, or remain otitis free. We propose to evaluate the role of specific immune responses to NTHi outer membrane proteins P2, P5, P6, and OMP26 in clearance of NP colonization by comparing children who clear colonization with those who experience prolonged colonization. In addition, we will establish a repository of prospectively collected mucosal and serum samples for other researchers in otitis media.
The specific aims of this research are:
Specific Aim 1 : To prospectively collect NP secretions, MEF, and sera from young children who are otitis prone, have infrequent otitis, or remain otitis free.
Specific Aim 2 : To evaluate the role of specific immune responses to NTHi P2, P5, P6, and OMP26 in clearance of AOM by comparing children with different AOM experiences and in clearance of NP colonization by comparing children with different colonization experiences.
Specific Aim 3 : To establish a repository of prospectively collected mucosal and serum samples for future research in otitis media. Relevance to Public Health: This project is specifically responsive to research needs identified at an NIAID and NIDCD-organized workshop held at the NIH on 8-9 June 2004 on """"""""Vaccines for Otitis Media: Proposals for Overcoming Obstacles to Progress."""""""" The results gained from these studies will provide insight to the immune mechanisms involved in the pathogenesis of otitis media aid in the development of a vaccine for otits media.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
7R01DC008671-03
Application #
7571627
Study Section
Immunity and Host Defense Study Section (IHD)
Program Officer
Watson, Bracie
Project Start
2007-03-01
Project End
2012-02-29
Budget Start
2009-03-01
Budget End
2010-02-28
Support Year
3
Fiscal Year
2009
Total Cost
$508,772
Indirect Cost

  Institution

Name
Rochester General Hospital (NY)
Department
Type
DUNS #
043078385
City
Rochester
State
NY
Country
United States
Zip Code
14621

  Publications

Almudevar, Anthony; Pichichero, Michael E (2018) Haemophilus influenzae-protein D specific antibody correlate with protection against acute otitis media in young children. Vaccine 36:1133-1135
Morris, Matthew C; Pichichero, Michael E (2017) Streptococcus pneumoniae burden and nasopharyngeal inflammation during acute otitis media. Innate Immun 23:667-677
Ren, Dabin; Murphy, Timothy F; Lafontaine, Eric R et al. (2017) Stringently Defined Otitis Prone Children Demonstrate Deficient Naturally Induced Mucosal Antibody Response to Moraxella catarrhalis Proteins. Front Immunol 8:953
Almudevar, Anthony (2017) A model for the regulation of follicular dendritic cells predicts invariant reciprocal-time decay of post-vaccine antibody response. Immunol Cell Biol 95:832-842
Surendran, Naveen; Nicolosi, Ted; Kaur, Ravinder et al. (2017) Prospective study of the innate cellular immune response in low vaccine responder children. Innate Immun 23:89-96
Xu, Q; Casey, J R; Almudevar, A et al. (2017) Correlation of higher antibody levels to pneumococcal proteins with protection from pneumococcal acute otitis media but not protection from nasopharyngeal colonization in young children. Clin Microbiol Infect 23:487.e1-487.e6
Ren, Dabin; Almudevar, Anthony L; Murphy, Timothy F et al. (2017) Serum antibody response to Moraxella catarrhalis proteins in stringently defined otitis prone children. Vaccine :
Pichichero, Michael E (2017) Pneumococcal whole-cell and protein-based vaccines: changing the paradigm. Expert Rev Vaccines 16:1181-1190
Xu, Qingfu; Wischmeyer, Jareth; Gonzalez, Eduardo et al. (2017) Nasopharyngeal polymicrobial colonization during health, viral upper respiratory infection and upper respiratory bacterial infection. J Infect 75:26-34
Morris, Matthew C; Nadeem Khan, M; Pichichero, Michael E (2017) A PCR-based method for quantifying neutrophils in human nasal secretions. J Immunol Methods 447:65-70

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