Determinants of Immunity against the Meningococcus

Neisseria meningitidis is a major cause of sepsis and meningitis worldwide, but is also a regular colonizer of the human nasopharynx. Invasive meningococcal infections are associated with high rates of morbidity and mortality, despite the availability of effective antibiotic treatment options. Vaccination is therefor the most effective way to protect people against N. meningitidis. Vaccines have been developed to target this bacterial pathogen since the early 1900’s, with varying levels of success. A successful meningococcal vaccine must be capable of preventing invasive N. meningitidis infections, to thereby protect the vaccinated individual from succumbing to infection. An ideal meningococcal vaccine should also prevent nasal colonization, thereby limiting the spread N. meningitidis and thus eliciting herd immunity within a vaccinated population. Within this thesis, I aimed characterize vaccine elicited immune processes necessary for protection against meningococcal nasal colonization and invasive sepsis. To characterize vaccine elicited protection against nasal colonization I took advantage of a “humanized” mouse model of N. meningitidis nasal infection, wherein expression of human CEACAM1 allows N. meningitidis to colonize the murine nose. I reveal that protection against nasal colonization is absolutely reliant on B cells and neutrophils, suggesting that opsonophagocytosis plays a major role in prevention of nasal colonization. To characterize vaccine elicited protection against invasive infections I utilized a mouse model of N. meningitidis sepsis. Previous findings haveiii revealed an important role for meningococcal specific IgG and complement activation in conferring protection against invasive infections. Here, I reveal that protection can occur in mice lacking either complement or IgG. Protection in the absence of complement relies on high antibody titer and my data suggests that phagocytic cells are necessary to clear the bacterial infection. Protection in the absence of IgG is reliant on bacterial specific IgM. Taken together, my findings provide novel insight into the mechanism of vaccine elicited protection against N. meningitidis. This mechanistic insight can be used to guide development of improved vaccines.

Department dc:contributor.department

Molecular Genetics

Year dc:date.issued

2021

Author dc:creator

• Currie, Elissa Glyn

Advisor dc:contributor.advisor

• Gray-Owen, Scott D

• complement
• herd immunity
• Neisseria meningitidis
• neutrophils
• vaccine

Statement dc:rights

• Attribution 4.0 International

Licence dc:rights.uri

• http://creativecommons.org/licenses/by/4.0/

Handle dc:identifier.uri

http://hdl.handle.net/1807/125883

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/125883