Analysis of serovar-specific immunity to Neisseria gonorrhoeae.
Author: Fudyk, Trevor Charles
Awarding University: University of Manitoba, Canada
Level : PhD
Holding Libraries: University Microfilms International ;
Advisors: Adviser: Simonsen, J NeilAbstract:
Infection with Neisseria gonorrhoeae constitutes an important cause of morbidity in human populations. The Porin protein (Por) is the major outer membrane protein of the gonococcus and displays considerable antigenic diversity among gonococcal strains. Two hypotheses to explain the diversity and dynamics of gonococcal populations is that protective, serovar- specific immunity, mediated by antibody to Por, develops following gonococcal infection, and that the development of protective immune responses within the core group act as a selective force for por antigenic heterogeneity in the gonococcal population. One core group in which gonococcal epidemiology has been studied extensively includes a collection of women working the commercial sex trade in the lower socioeconomic district of Pumwani in Nairobi, Kenya. Two experimental strategies were used to evaluate these hypotheses in a more recent longitudinal study of these female, sex workers in Nairobi, Kenya. The first line of experiments sought to examine the nature and distribution of genetic polymorphism in the Por genes of the gonococcal serovars infecting the Nairobi cohort. Nucleotide substitutions were observed predominantly in surface-exposed encoding segments of the 1a and 1b por genes. The majority of substitutions, particularly those occurring in surface- exposed encoding gene segments, resulted in amino acid change. The second line of experiments sought to determine the effect of the antibody response to por on serovar-specific gonococcal infection. Cohort women were assayed for baseline antibody responses to a recombinant 1b2 porin and a collection of polypeptides corresponding to 1b Por surface-exposed loops and followed longitudinally for gonococcal infection. Overall, antibody to the 1b2 porin appeared to provide limited protection from 1b infection, although this protective effect did not appear to extend to infection with 1a serovars. Women with antibody to 1b2 Por experienced significantly fewer homologous 1b2 and heterologous 1b3 serovar infections, compared to women without antibody. The data observed in this study support the hypothesis that the humoral immune response to Por is an important component in the ecologic interaction of human and gonococcal populations, while the generation of antigenically diverse pathogen populations act a mechanism to ensure endemic infection and pathogen survival in the face of this immune barrier. (Abstract shortened by UMI.)