No description available.

Development of an improved TB vaccine is hindered by the lack of a correlate of ,~.-r protection. Efficacy of TB vaccines in humans can only be a"S~essed by expensive and time consuming trials within TB endemic areas, which are limited; therefore, it is critical that vaccines with the greatest potential to protect are selected for these trials. Mycobacterial growth inhibition assays (MGIAs) have been developed with the hope that these in vitro functional assays will correlate with protection, which could aid in the selection of the best vaccine candidates. Work in this thesis describes the development and evaluation of different MGIAs for their ability to detect TB vaccine induced mycobacterial growth inhibition. The mycobacterial growth indicator tube (MGIT) MGIA reproducibly demonstrated mycobacterial growth inhibition in splenocytes from BCG vaccinated compared with naive mice, which corresponded with in vivo protection from M. tb challenge. This assay also discriminated between PBMC from naive and BCG/BCG-MVA85A vaccinated macaques. Microarray data showed extensive differential gene expression in splenocyte responses to ex-vivo BCG stimulation between naive and BCG vaccinated mice. T H 1 responses including IFN-y with NOS2 expression were enhanced in BCG vaccinated mice, indicating a possible mechanism for mycobacterial growth inhibition in BCG vaccinated mice. Further investigation into whether the MGIT assay can be used as a correlate of protection from M. tb in humans and animals is warranted.

A Research report submitted to the Faculty of Health Sciences, University of Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Medicine in Paediatrics Johannesburg 2015 / Children hospitalized with culture-confirmed pulmonary tuberculosis (PTB) frequently present with acute symptoms, possibly because underlying PTB may predispose to superimposed bacterial pneumonia. Immunization of children with pneumococcal conjugate vaccine (PCV) could protect against such superimposed bacterial pneumonia and reduce the incidence of PTB hospitalization. OBJECTIVE We studied the temporal association of childhood immunization with pneumococcal conjugate vaccine on the incidence of hospitalization for culture-confirmed PTB in children. METHODS A retrospective study on the incidence of hospitalization for culture-confirmed childhood PTB at Chris Hani Baragwanath Academic Hospital was undertaken from 2005 to 2012. This included a pre-PCV era (2005-2008) and a PCV era (2011-2012). RESULTS Overall, there was a 69.2% (95% CI: 62.8-74.6%) decline in the incidence of hospitalization for culture-confirmed PTB when comparing the PCV and pre-PCV-eras, with the decline in HIV-uninfected children only significant in the 3-11 month age category and the decline in HIV-infected significant across all age categories. There was a trend for reduced pneumococcal bacteraemia in the PCV era compared to the pre-PCV era, with the odds of having a blood culture positive for pneumococcus being 1.91-fold (95% CI, 0.26-84.56) greater in the Pre-PCV era. CONCLUSION There has been a significant decline in culture-confirmed PTB hospitalization in children comparing the pre-PCV to the PCV-era. However, the incidence of culture-confirmed PTB prior to the introduction of PCV had been reduced to low levels due to antiretroviral therapy. This confounder together with the retrospective ecological study design and other several possible confounders limited any robust estimate as to whether there was a temporal association between PCV immunization and incidence of culture-confirmed PTB hospitalization in our study setting.

An oral Vibrio vaccine for salmonids was developed. The vaccine was produced by spray coating lyophilized formalin-killed whole cells of Vibrio anguillarum (VA LS 1- 74) onto non-pareil sugar beads. Then methacrylic acrylic acid copolymer (Eudragit L-30D) was applied as an enteric protective coating. Using x-ray radiographic techniques, it was found that large particles (> 1.1 mm) remain in the fish stomach for more than 2 hours before they would enter the pyloric caeca. The pyloric sphincter which has an opening of 0.94 mm, acts as barrier to prevent the passage of large food particles in the stomach to the pyloric caeca. Based on this information non-pareil sugar beads of 18-20 mesh or smaller should be used as the vaccine carriers. A 15% (w/w) Eudragit L-30D coating is needed to provide enteric protection of the vaccine loaded sugar beads of 18-20 mesh size. Lower levels of coating resulted in the bead breaking down in the stomach and releasing contents prior to entering the pyloric caeca. Since the lymphoid tissues are diffuse throughout the whole GI tract, it may not be necessary to target a vaccine to deliver antigens to a specific area of the intestinal tract, but only protect the antigens from gastric fluids. In vitro dissolution studies indicate that 10% VA LS 1- 74 loading was sufficient for rapid vaccine release (42% released in 30 minutes) and a 15% Eudragit L-30D coating was suitable for providing protection against stomach acid. The vaccine product used in vivo studies contained 10% VA LS 1- 74 and 15% Eudragit L-30D on non-pareil sugar seeds of 18-20 mesh size. Coho salmon were given the vaccine orally, and 30 days afterward a live challenge test was performed. There was no significant difference in the survival rates in a live bacteria challenge test with the positive control (83.3%) and test (80.3%) groups. Both had higher survival rates than the no vaccine fed control group. The serum and mucosal antibody levels to Vibrio were significantly higher (p<0.01) in the test group (19700 units/ml) than the other two groups (2530 units/ml in the positive control group and 617 units/ml in the negative control group). The antibody titer appears to be a better indicator for vaccine efficacy than survival rate of live bacteria challenge tests. The oral Vibrio vaccine developed is effective, and the technique to protect the antigen can be applied to other antigens or proteins for oral delivery producing an economical pathway for mass vaccination of fish. / Graduation date: 1991

Thesis (Ph.D.)--University of Adelaide, Dept. of Paediatrics, 2002? / Includes list of publications arising from the thesis. Bibliography: leaves 327-341.

No description available.

Members of the family Chlamydiae cause a wide range of diseases. Chlamydia trachomatis and C. pneumoniae are most commonly associated with human disease. C. psittaci and C. pecorum are largely animal pathogens, although C. psittaci can cause pneumonia in the elderly and immunocompromised. A vaccine against these pathogens is desirable, but although multiple vaccine regimens have been examined, none have proven truly effective. Studies were conducted to evaluate the use of recombinant vaccinia virus (VV) vectors encoding chlamydial proteins as vaccine candidates using a guinea pig model. In the first study, guinea pigs were immunized with varying amounts of attenuated VV encoding either the M6 protein of Streptococcus pyogenes or chloramphenicol acetyl transferase (CAT) from E. coli. The purpose of this study was: (1) determine how much attenuated virus can be given intranasally to guinea pigs without causing death; (2) characterize the humoral and secretory antibody response to both the viral vector and M6 protein; and (3) develop a protocol for animal manipulation, and sample collection and storage for use in future research. The results obtained indicate that 10⁹ PFU of attenuated VV can be given intranasally to guinea pigs. Serum IgG was detected against VV proteins, as determined by immunoblotting. Antibodies against M6 could not be similarly detected in serum, or by direct enzyme linked immunosorbant assay (ELISA). IgG could not be detected by immunoblotting against either VV or M6 in saliva. The purpose of the second part of this research was to evaluate the potential efficacy of a vaccine using the C. psittaci guinea pig inclusion conjunctivitis (GPIC) strain proteins IncA and TroA. Guinea pigs were immunized intranasally with either PBS, control vaccinia virus, rVV:IncA, or rVV:TroA. Three weeks after immunization animals were challenged by ocular infection with C. psittaci elementary bodies (EBs). Eye swabs were taken following challenge and titered to determine the chlamydial load. Results indicate that rVV:TroA provides no protection against chlamydial challenge. Titers from rVV:IncA immunized animals appeared to be somewhat lower than those of the controls on day 4 post-challenge. This difference, however, proved not to be statistically significant. A single immunization with rVV:IncA or rVV:TroA was thus shown not lead to a protective immune response in guinea pigs under the conditions tested. / Graduation date: 2002

Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2003. / Includes bibliographical references (leaves 112-129). Also available in electronic version. Access restricted to campus users.

Thesis (Ph. D.)--Rutgers University, 2007. / "Graduate Program in Pharmaceutical Science." Includes bibliographical references (p. 167-189).

Thesis (M. Phil.)--University of Hong Kong, 1999. / Includes bibliographical references (leaves 134-158).