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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC008671-04
Application #
7781328
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
2010-03-01
Budget End
2011-02-28
Support Year
4
Fiscal Year
2010
Total Cost
$491,882
Indirect Cost
Name
Rochester General Hospital (NY)
Department
Type
DUNS #
043078385
City
Rochester
State
NY
Country
United States
Zip Code
14621
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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, 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
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
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Pichichero, Michael E; Almudevar, Anthony (2016) Serum cytokine biomarkers accurately predict presence of acute otitis media infection and recovery caused by Haemophilus influenzae. Int J Pediatr Otorhinolaryngol 83:200-4
Pichichero, Michael E (2016) Ten-Year Study of the Stringently Defined Otitis-prone Child in Rochester, NY. Pediatr Infect Dis J 35:1033-9
Morris, Matthew C; Kozara, Kevin; Salamone, Frank et al. (2016) Adenoidal follicular T helper cells provide stronger B-cell help than those from tonsils. Laryngoscope 126:E80-5
Ren, Dabin; Pichichero, Michael E (2016) Vaccine targets against Moraxella catarrhalis. Expert Opin Ther Targets 20:19-33
Surendran, Naveen; Nicolosi, Ted; Pichichero, Michael (2016) Infants with low vaccine antibody responses have altered innate cytokine response. Vaccine 34:5700-5703

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