{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/80847"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/80847","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Nontypeable Haemophilus Influenzae Genomes Reveal Vaccine Antigen Genetic Diversity and a Novel Host Cell Invasin","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Ahearn, Christian"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Murphy, Timothy","Microbiology and Immunology"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-10-29T16:47:30Z","date_published":"2019-10-29T16:47:30Z","updated_at":"2026-07-27T19:05:25Z","subjects":["microbiology","molecular biology","biochemistry"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/80847","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Murphy, Timothy","Microbiology and Immunology"]},{"key":"dc:creator","label":"Author","values":["Ahearn, Christian"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-10-29T16:47:30Z","2019","2019-07-12 16:45:36"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["microbiology","molecular biology","biochemistry"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/80847"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","Nontypeable Haemophilus influenzae (NTHi) is an exclusively human pathobiont. NTHi opportunistically infects the lower airways of adults with chronic obstructive pulmonary disease (COPD), which causes morbidity and mortality in these individuals. Antibiotic treatment reduces symptoms of infection, but does not prevent against subsequent infection. Thus, identification of ideal candidate antigens for use in an NTHi vaccine is an active area of research. Genetic diversity of NTHi strains and antigenic variation of NTHi proteins presents issues for identifying NTHi candidate vaccine antigens. Using the genome sequences of NTHi strains that persisted in the lower airways of adults with COPD for months to years we determined the conservation and diversity of 12 current candidate vaccine antigens, which are at varying stages of preclinical studies and clinical trials. We observed that the P6, OMP26, PD and PF antigen sequences were invariant during persistent infection and highly conserved among strains, which are ideal characteristics of NTHi vaccine antigens. The Hap, D15, P5 and P2 antigens were genetically diverse, experienced sequence changes during persistence and contained amino acids under positive selection, indicating that these are not ideal vaccine candidate antigens. A strategy of NTHi vaccine development is to target NTHi virulence factors, which blocks their function and prevents NTHi from causing infection. Genome mining of the persistent strains identified the conserved and invariant antigen NTHI1441. Here we determined that NTHI1441 was involved in invasion of host respiratory epithelial cells, bacterial cell aggregation, and biofilm formation, which are virulence mechanisms used by NTHi to persist in the lower airways of adults with COPD. In total, this work identified NTHi vaccine antigen stability during persistent infection of the COPD airways, and characterized a novel NTHi antigen involved in virulence, which shows potential as a target for therapeutic and preventative interventions."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Nontypeable Haemophilus Influenzae Genomes Reveal Vaccine Antigen Genetic Diversity and a Novel Host Cell Invasin"]}]}],"canonical_facts":{"dc:contributor":["Murphy, Timothy","Microbiology and Immunology"],"dc:creator":["Ahearn, Christian"],"dc:date":["2019-10-29T16:47:30Z","2019","2019-07-12 16:45:36"],"dc:description":["Ph.D.","Nontypeable Haemophilus influenzae (NTHi) is an exclusively human pathobiont. NTHi opportunistically infects the lower airways of adults with chronic obstructive pulmonary disease (COPD), which causes morbidity and mortality in these individuals. Antibiotic treatment reduces symptoms of infection, but does not prevent against subsequent infection. Thus, identification of ideal candidate antigens for use in an NTHi vaccine is an active area of research. Genetic diversity of NTHi strains and antigenic variation of NTHi proteins presents issues for identifying NTHi candidate vaccine antigens. Using the genome sequences of NTHi strains that persisted in the lower airways of adults with COPD for months to years we determined the conservation and diversity of 12 current candidate vaccine antigens, which are at varying stages of preclinical studies and clinical trials. We observed that the P6, OMP26, PD and PF antigen sequences were invariant during persistent infection and highly conserved among strains, which are ideal characteristics of NTHi vaccine antigens. The Hap, D15, P5 and P2 antigens were genetically diverse, experienced sequence changes during persistence and contained amino acids under positive selection, indicating that these are not ideal vaccine candidate antigens. A strategy of NTHi vaccine development is to target NTHi virulence factors, which blocks their function and prevents NTHi from causing infection. Genome mining of the persistent strains identified the conserved and invariant antigen NTHI1441. Here we determined that NTHI1441 was involved in invasion of host respiratory epithelial cells, bacterial cell aggregation, and biofilm formation, which are virulence mechanisms used by NTHi to persist in the lower airways of adults with COPD. In total, this work identified NTHi vaccine antigen stability during persistent infection of the COPD airways, and characterized a novel NTHi antigen involved in virulence, which shows potential as a target for therapeutic and preventative interventions."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/80847"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["microbiology","molecular biology","biochemistry"],"dc:title":["Nontypeable Haemophilus Influenzae Genomes Reveal Vaccine Antigen Genetic Diversity and a Novel Host Cell Invasin"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:25Z"}