DNA-based vaccines represent a novel method of immunization that has been demonstrated to induce immune responses in animals against a variety of plasmid encoded antigens and following a number of different methods of vaccine delivery. We characterized the immune response to DNA-based vaccines encoding intracellular, membrane anchored (cell associated) and extracellular (secreted) forms of glycoprotein D (gD), an antigen from the viral envelope of the bovine herpesvirus-1 (BHV-1). Intramuscular injection of mice with plasmids encoding secreted or cell associated forms of this antigen led to seroconversion and a predominance of splenic IFN ã. Mice receiving plasmids encoding cell associated or secreted antigens displayed a predominance of IgG2a and IgG 1, respectively. The predominant serum isotype correlated with the cytokine and antibody isotype profiles within the draining lymph node. We demonstrated modulation of immune responses in mice following co-delivery of plasmids encoding a secreted form of gD and each of eight different murine cytokines (IL-1á, IL-12, IL-4, IL-6, IL-10, GM-CSF, IFN ã, TNF á). Plasmids encoding GM-CSF, TNF á, IL-4 and IL-6 demonstrated the capacity to enhance serum IgG titers and seroconversion efficiency. Plasmids encoding IFN ã and TNF á increased levels of serum IgG2a in mice. Varying the dose of plasmids encoding GM-CSF enhanced (10 [mu]g) or suppressed (50 [mu]g) serum antibody levels and induced significant increases in IL-4 levels in the spleen and draining lymph nodes. High doses of GM-CSF (50 [mu]g) increased the levels of serum IgG2a after boosting. Co-administration of plasmids encoding IFN ã either reduced (10 [mu]g) or enhanced (50 [mu]g) serum antibody levels and elevated mean serum IgG 2a levels. Finally, we investigated the potential for plasmids encoding the secreted form of gD to elicit immune responses in passively immune mice. We demonstrated that a single intramuscular immunization of passively immune C3H.HeN or C57BL/6 mice with plasmids encoding the secreted form of BHV-1 gD resulted in the development of both cell-mediated and humoral immunity.

Background: Human papillomavirus vaccination is newly developed in this decade. There are 2 types of vaccines. Bivalent vaccine targets on HPV types 16, 18 to prevent cervical cancer. Quadrivalent vaccine target on HPV type 6, 11, 16, 18 to prevent genital warts and cervical cancer. England has adopted a population –based HPV vaccination program. In attempt to find out the worthiness to implement the population-based vaccination program in Hong Kong, this project reviewed 15 cost-effectiveness analyses in Asian countries. Asian countries may have the similar characteristics, such as culture, sex behavior, genome, etc, that makes the result more applicable to Hong Kong. Methodology: Cost-effectiveness analysises of human papillomavirus vaccination were identified by the searching engine MEDLINE (Ovid) by using relevant keywords. All English and Chinese articles relevant to the topic were identified. Articles conducted for the cost-effectiveness of human papillomavirus vaccine in Asian countries were considered as the potential literature for the review. Result and Discussion: The searching engine identified 259 literatures, 16 of them are in Asian countries, 1 of them did not meet the criteria of quality assessment. 15 of them are included in this review. 6 different model approaches were used in the 15 articles. Results from the same countries in 2 separated articles were heterogeneous. That may probably due to the different assumption and perspectives used. Different perspectives would include different costing. Studies only including the direct cost would likely over-estimate the cost-effectiveness of the vaccine. The threshold value adopted would also affect the result. A stricter threshold value would under-estimate the cost-effectiveness. Some low-and-middle income countries has no available data on the vaccination because the vaccine is not available in the market, the data would only rely on the past literature or international data. 12 out of the 15 studies showed that the vaccination is cost-effective in the countries. Conclusion and Implication: the ICER is sensitive to the price of the vaccine, the efficacy, the duration of protection, the discount rate, the screening coverage rate, and the age of receiving vaccination, the vaccination coverage rate and the cervical cancer or genital warts incidence rate. Some studies showed that regular screening combined with vaccination program would be cost-effective. In the studies comparing the 2 types of vaccines, all the results showed that quadrivalent vaccine dominant to the bivalent vaccine. Moreover, the vaccination would decrease the cervical cancer incidence by 20% to 90%. In view of the prevalence of HPV type and the high incidence rate of genital warts. The quadrivalent vaccine is likely beneficial to Hong Kong / published_or_final_version / Public Health / Master / Master of Public Health

Includes list of publications arising from the thesis. / Bibliography: leaves 327-341. / 341, [15] leaves : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examines the effect of adverse storage on the immunogenicity of pertussis, diphtheria and tetanus vaccines, the protective efficacy of pertussis vaccines and the effect of premature birth on antibody response to routine childhood immunisations. / Thesis (Ph.D.)--University of Adelaide, Dept. of Paediatrics, 2002?

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Hong Kong, 1996. / Cover title. Includes bibliographical references.

Thesis (M.N.) -- Memorial University of Newfoundland, 2003. / Typescript. Bibliography: leaves 125-131. Also available online.

The neuroparalytic syndrome called botulism is caused by the neurotoxins produced by bacteria in the genus Clostridium. There are seven toxigenic types of C. botulinum (A to G) based on antigenically distinct toxins produced by different strains of the organism. Animal botulism is caused by C. botulinum type C and D neurotoxins and has a severe economic impact on cattle farming in South Africa and neighbouring countries. Current treatment regimes include the use of acetylcholine for symptomatic treatment, but this is unfortunately very seldom successful. All indications are that there is no cure for this disease and that effective control can only be achieved through development of efficacious vaccines. The botulinum vaccine currently in use in South Africa contains an adjuvanted toxoid form of the type C and o neurotoxins. However, this bivalent vaccine relies on problematic anaerobic cultivation of the Clostridium bacterium followed by isolation, purification and inactivation of the toxin by treatment with formalin. Apart from the fastidious growth requirements of this organism, it has been reported that the production of toxin by these cells declines rapidly and eventually ceases, following laboratory passaging of the bacterial cultures. In addition, improper inactivation of the toxins may also lead to the demise of animals following vaccination. Thus, there exists a great need for a safe, effective and inexpensive vaccine against botulism. To investigate the potential of types C and D botulinum neurotoxins as efficacious recombinant vaccine candidates against botulism, full-length copies of the genes were obtained by polymerase chain reaction (PCR) amplification from bacteriophage DNA isolated from Clostridium botulinum type C (Stockholm) and D (South Africa) cultures. The full-length genes were cloned and subsequently sequenced to verify their integrity. By making use of PCR-based site-directed mutagenesis procedures, three amino acid mutations were introduced in the zinc-binding motif of the respective neurotoxins. Mutation of this domain has previously been reported to successfully detoxify type C neurotoxin. The wild-type and mutant genes were subsequently expressed in insect cells using the BAC-to-BAC™ baculovirus system. Although, unique protein bands corresponding to the size of the neurotoxins could not be seen in Coomassie brilliant blue-stained gels, Western blot analysis indicated immunoreactive material for wild-type and mutant type C corresponding to the size of the type C toxin light chain. However, there was no conclusive evidence to support the successful expression of the full-length wild-type and mutant type D genes. / Dissertation (MSc (Microbiology))--University of Pretoria, 2006. / Microbiology and Plant Pathology / unrestricted

Streptococcus pneumoniae is typically an asymptomatic colonizer of the upper respiratory tract but can cause invasive disease in susceptible populations. Pneumococcal vaccines which are currently in use have failed to significantly reduce colonization by S. pneumoniae. To control invasive pneumococcal disease, novel strategies must be utilized. One such strategy is to reduce or eradicate colonization by pneumococcus. Supplementary vaccination with pneumococcal proteins important for colonization could serve to prime the immune system against these targets. This study serves as an initial step towards identification of crucial pneumococcal colonization proteins which may previously have been uncharacterized. Assessing the immune reactivity of human serum to isolated pneumococcal membrane proteins allowed for selection of proteins for analysis via mass spectrometry. Results of MS produced several potential protein targets for further research. Identification of these key surface proteins will pave the way for the creation of a more robust supplementary vaccine, and an improved understanding of the role of non-immunogenic pneumococcal surface proteins.