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.

published_or_final_version / Community Medicine / Master / Master of Public Health

published_or_final_version / Nursing Studies / Master / Master of Nursing

The ectodomain of influenza matrix protein 2 (M2e) may be an ideal candidate in the development of influenza universal vaccine due to its highly conserved property among different subtypes/strains of influenza virus. M2e based vaccines have been extensively studied and potent cross-subtype/strain protections have been reported. However, more and more M2e mutants of influenza virus have been identified in recent years. It is still unclear whether M2e based vaccines are effective against these M2e mutants of influenza virus. This study first evaluated cross-protection of an M2e tetrameric peptide vaccine based on H5N1 virus strain A/Vietnam/1194/04 (VN/1194-M2e) against lethal challenges of M2e mutants of H5N1 virus strain A/Hong Kong/156/97 (HK/156) and a novel H7N9 virus, because there are 3 or 5 amino acid differences between VN/1194-M2e and HK/156-M2e or VN/1194-M2e and H7N9-M2e. The results showed that the vaccination of VN/1194-M2e did not induce high level of cross-reactive antibodies against HK/156-M2e and just provided poor cross-protection against lethal challenge of HK/156 virus. In contrast, VN/1194-M2e vaccination induced high level of cross-reactive antibodies against H7N9-M2e. Consistently, the vaccination provided good cross-protection against lethal challenge of H7N9 virus. These results strongly suggested that some mutations in M2e, such as mutations at positions 10, 14 and 16 which found in HK/156 M2e, might affect the M2e vaccine efficacy, but some others, such as five mutations found in H7N9-M2e, might not be critical for the M2e immunogenicity. This study then investigated the relationship between the M2e immunogenicity and amino acid mutations of the M2e. Beside VN/1194-M2e (P0), we synthesized additional 10 M2e mutant peptides which contain different single or multiple mutations. The 3D structures of these M2e peptides were predicted and analyzed. The prediction results showed that group 1 peptides (P0, P10, P14, P16, P18, P20 and P18-20) exhibited either irregular structures or loose hairpin structures which might associate with well exposure of antigenic epitope, whereas group 2 peptides (P10-14, P10-16, P14-16 and P10-14-16) formed tight hairpin structures in which antigenic epitope might bury inside their own secondary structure. Vaccination efficacies of these M2e peptides were evaluated in mice for antibody responses and cross-protection against lethal challenge of VN/1194 and HK/156 viruses. Our results showed that vaccinations of group 1 peptides induced high levels of cross-reactive antibodies against VN/1194-M2e and good cross-protection against lethal challenge of VN/1194 virus. However, vaccinations of group 2 peptides vaccinations induced significantly lower VN/1194-M2e antibody responses and poor cross-protection against lethal challenge of VN/119 virus. Furthermore, both group 1 and group 2 peptides could just induce low levels of cross-reactive antibodies against HK/156-M2e and poor protection against lethal challenge of HK/156 virus. Although H5N1-M2e tetrameric peptide has been previously shown to protect mice from lethal challenges by different subtypes/strains of influenza virus, this study has shown that certain amino acid variations in M2e could weaken M2e immunogenicity but some others might not. The different secondary structures of M2es may probably associate with their immunogenicity. Our findings have provided valuable information for the development of M2e based universal vaccines. / published_or_final_version / Microbiology / Doctoral / Doctor of Philosophy

published_or_final_version / Nursing Studies / Master / Master of Nursing

Backgrounds: Receive seasonal influenza vaccination is the most safe and effective way to prevent seasonal influenza and its complications. According to the WHO, the number of hospitalizations among older people due to influenza could be reduced by a ranged from 25% to 39% as a result of vaccination. It has also been revealed to reduce overall mortality rate of the influenza seasons by a range from 39% to 75%. Moreover, influenza vaccination protects almost 90% healthy adults against clinical disease in industrialized countries, under the precondition that the vaccine antigens and circulating viruses are well matched with each other. However, the prevalence of elderly Chinese people undertaking influenza vaccination is still sub optional, the percentage of which is 62.4%. Previous researches reveal that there are a number of reasons for non-compliance to influenza immunization, including the unfavorable side-effects, doubt to the effectiveness of the vaccine, the fear of needles, as well as unawareness of the seriousness of flu. These are all factors associated with personal willingness. Aims and objectives: The aims of this paper are to explore factors that influence vaccination rate in older people and to examine other countries’ experience to identify useful policies. The specific objectives are: 1. To identify from the published literature factors which contribute either positive or negative impacts on vaccination rates in older people. 2. To group these factors into appropriate categories. 3. To make suggestions on policies to improve vaccination rates based on the identified factors and other countries’ experience. Methods: Relevant publications were achieved through PUBMED. Search strategies as well as criteria for inclusion and exclusion had been predetermined and applied. Analysis includes both community perception factors and interpersonal factors. Results: 17 English literatures were reviewed, revealing predictors of seasonal influenza vaccination for and against, which could be grouped into four categories: Factors relate to demographic, factors relate to Health Belief Model, factors relate to social support, factors relate to advice and information being provided. Conclusion: According to this literature review, demographic factors, factors relate to Health Belief Model, social support and information being provided are revealed to be associated with the elders’ inclination to get influenza vaccination. / published_or_final_version / Public Health / Master / Master of Public Health

Influenza vaccination is the best preventive measure against influenza virus infection, and antivirals including oseltamivir are effective treatments. From a public health point of view, it is important to evaluate whether vaccination and antiviral treatment reduces transmission of the virus. I analyzed data from a community-based study of influenza virus transmission in households, and identified effectiveness of antiviral treatment in reducing duration of illness and some evidence that treatment reduced transmission to household contacts. I also analyzed data from a community-based placebo-controlled trial of influenza vaccination and confirmed efficacy of vaccination against seasonal influenza but differential efficacy against pandemic influenza possibly because of timing and mediation of seasonal influenza epidemics. In further analyses I found that antibody titers of 1:40 correlated with 50% protection against infection, and repeated vaccination with the same strains tended to be associated with reduced responses to those strains although there was no evidence of reduced efficacy. In the study, one child in each household was randomly allocated to receive vaccine or placebo and I did not identify any evidence of indirect benefits to the household members of vaccinated children. I reviewed vaccine target groups in different countries, and noted that some countries now include school-age children in their target groups based mainly on the principle of herd immunity. My findings did not support the inclusion of school-age children as a target group for vaccination in Hong Kong. Further studies should examine the indirect as well as direct benefits of vaccination in different settings in order to guide optimal influenza vaccination policies. / published_or_final_version / Community Medicine / Doctoral / Doctor of Philosophy

Thesis (M. P. H.)--University of Hong Kong, 2008. / Includes bibliographical references (leaf 89-94) Also available in print.

Thesis (D.P.H.)--University of Michigan.