Influenza has been one of the most infectious diseases for roughly 2400 years. The most effective way to prevent influenza outbreaks and eliminate their seasonal effects is vaccination. The distribution of influenza vaccine to various groups in the population becomes an important decision determining the effectiveness of vaccination for the entire population. We developed a simulation model using the Epifire C++ application program [2] to simulate influenza transmission under a given vaccination strategy. Our model can generate a network that can be configured with different degree distributions, transmission rates, number of nodes and edges, infection periods, and perform chain-binomial based simulation of SIR (Susceptible-Infectious-Recovered) disease transmission. Furthermore, we integrated NOMAD (Nonlinear Optimization by Mesh Adaptive Direct Search) for optimizing vaccine allocation to various age groups. We calibrate our model according to age specific attack rates from the 1918 pandemic. In our simulation model, we evaluate three different vaccine policies for 36 different scenarios and 1000 individuals: The policy of the Advisory Committee on Immunization Practices (ACIP), former recommendations of the Centers for Disease Control and Prevention (CDC), and new suggestions of the CDC. We derive the number of infected people at the end of each run and calculated the corresponding cost and years of life lost. As a result, we observe that optimized vaccine distribution ensures less infected people and years of life lost compared to the fore-mentioned policies in almost all cases. On the other hand, total costs for the policies are close to each other. Former CDC policy ensures slightly lower cost than other policies and our proposed in some cases.

Even though influenza vaccinations were provided free to all healthcare workers in the United States, healthcare workers were not 100% compliant. The non-compliance with influenza vaccinations may expose their patients, their families, and the public at large to a high-risk source of influenza infection. This study's research questions included how registered nurses perceived influenza and influenza vaccination; registered nurses' self-reported incidents with influenza vaccination; and factors that contributed to registered nurses' non-compliance with influenza vaccination. Guided by the theory of reasoned action and the theory of planned behavior, the purpose of this qualitative study was to determine the factors that contributed to the non-compliance of registered nurses with receiving the influenza vaccination. Twenty participants from a healthcare facility in Florida were interviewed using an interview guide. Audio data was transcribed to text data; text data was coded and thematically analyzed by using ATLAS.ti software. Results revealed that 70% of registered nurses were afraid of influenza vaccination, while 80% of them saw influenza vaccination as ineffective; 90% of them had bad experiences or have seen colleagues/friends who have had bad experiences after influenza vaccination. In addition, 40% of registered nurses claimed that they already had good immunity, while 20% of them declined influenza vaccination because of personal choices. Research findings from this study may be utilized to bring positive social change to society at large. The findings may be utilized to enhance existing strategies or policies or even help formulate new policies and strategies that would address the concerns of HCWs, especially registered nurses.

Foreign and domestic researches reveal that influenza vaccine is safe and can effectively reduce related healthy trouble caused by influenza in the elderly, infant and high-risk population, etc. The main purpose of ¡§Influenza vaccine policy¡¨ is public service. To promote concepts of citizenism and consumer-right brings the concept of marketing. With the progress of democratic trend, when policies are discussed, planned, established and executed, the government should consider policies as ¡§products¡¨ to sale and emphasize policy-marketing concept to gain public approval and acceptance. This study was based on influenza vaccine policy carried out by Centers for Disease Control, R.O.C. (Taiwan). In accordance with the marketing framework of public policy advocated by Snavely (1991), we designed a questionnaire investigation on surveying citizen and medical staff of Kaoshiung to see if government vaccine policies can grasp the important path as well as positive effectiveness of policy marketing, and issued our research outcomes on promoting prevention and cure of vaccine to be part of references for government health center. The results of descriptive statistics displayed that 80% of survey candidates regardless of common people or medical practitioners possessing professional knowledge agreed that influenza vaccine was an outstanding policy and approved the government¡¦s response and clarification in facing medial negative report. 60% of survey candidates were affected and worried about safety of influenza vaccine, after receiving these medial negative reports. Former experience of vaccination would considerably affect the willingness of general public to receive a flu shot. Survey candidates mainly received information about influenza vaccine from television media and preferred to approve either experts or endorsers. Results of Chi-square test showed that there was a significant correlation between ¡§influenza vaccination¡¨ and common people¡¦s experience of suffering from chronic disease or unhealthy inoculable response. Results of independent-samples T test and one-way ANOVA indicated the factors correlating significantly with the analytic variables of approval of degree ¡§service¡¨ in marketing mix program. In the case of common people, these factors included the following variables such as ¡§those who had ever been vaccinated¡¨, ¡§those who had ever been vaccinated and suffered from bad inculable response¡¨, and ¡§those who had ever participated health education during the past year¡¨. In respect of medical practitioners, these factors included the following variables such as ¡§those who had ever been vaccinated and suffered from bad inculable response¡¨ and ¡§those who had ever taken the thematic speech, related websites or webpages¡¨. With regard to analytic variables of approval of degree ¡§cost¡¨ in marketing mix program included following factors. For common people, the factors contained ¡§those who had ever been vaccinated and suffered from bad inculable response¡¨, and ¡§those who had ever participated health education, related bulletin board and scrolling text marquee during the past year¡¨. For medical practitioners, the factors comprised ¡§those who had ever been vaccinated and suffered from bad inculable response¡¨ and ¡§those who had ever taken thematic speech, related vedio, websites or webpages¡¨ As for analytic variables of approval of degree ¡§supply of information and education¡¨ in marketing mix program included following factors. For common people, the factors contained ¡§those who had ever been vaccinated¡¨, and ¡§those who had ever participated related bulletin board, scrolling text marquee, thematic speech, TV vedio, broadcasts, websites or webpages during the past year¡¨. For medical practitioners, the factors comprised ¡§occupation¡¨ and ¡§those who had ever perused related books, journals, newspaper, websites or webpages¡¨. Policy marketing concept should not be neglected in the application of executing public policy. For influenza vaccination policy marketing, first of all, public mental barriers of safety of influenza vaccine must be overcome, therefore the most critical issue is to enhance advertisement and education about safety of vaccine in order to improve confidence of public for influenza vaccine and to prevent from the loophole of influenza prophylaxis and treatment. This study suggests that we must to adopt consumer-driven marketing concept for the influenza vaccine policy marketing mix program. Government public relations should establish harmonious media relations and use higher acceptance of promotion way to focus on the limited resources to target market. We should make concise and rememberable messages and integration marketing communication way to achieve the comprehensive effect. We expect that the government performs policy marketing to promote the public approval of ¡§influenza vaccine policy¡¨ and to raise influenza vaccination rate on diminishing influenza morbidity and mortality rate.

The seasonal influenza (flu) vaccine has been shown to prevent flu outbreaks that can cause debilitating effects on the body and even death. Underserved members of Black communities are more likely to refuse the flu vaccine than are persons of other ethnicities. The purpose of the project was to determine from a needs assessment the reasons for flu vaccine refusal in the Black population of an inner city clinic in order to develop tailored communication and nursing actions that promote awareness of the flu vaccine's importance and safety. The health belief model constructs (perceived susceptibility, perceived severity, perceived benefits, and perceived barriers) were used to guide the project. A survey based on the constructs of the health belief model was administered to a convenience sample of 40 adult patients in an inner city clinic who completed the anonymous survey while they waited for the physician. Descriptive statistics showed that adults ages 18 to 36, who were the largest group of respondents (n = 33), agreed to be vaccinated and believed the flu to be a serious disease for their age group. Reported barriers to vaccination included finding time to get vaccinated and the belief that the vaccine causes the flu. The findings supported development of an annual seasonal flu vaccine campaign that included verbal and written education, informational posters, social media messages, and a standing order to offer and administer the injection to all adults served by the practice. Social change implications are expected to include decreased morbidity and mortality from flu among the Black inner city patients and closer alignment of the clinic with the Healthy People 2020 vaccination goals.

Although there are well-documented benefits from influenza vaccine and 23-valent pneumococcal polysaccharide vaccine (23vPPV) against invasive pneumococcal disease and laboratory confirmed influenza, their effectiveness against pneumonia remains controversial for community-based persons aged >=65years. At the time of this research, within Australia, only the government of Victoria publicly funded these vaccines for elderly persons. With continued growth of the elderly population, the subsequent adoption of an Australia-wide program, and increasing uptake of similar programs in other countries, there is a need for data clarifying the impact of vaccination on pneumonia. This research estimates incremental vaccine effectiveness of 23vPPV over and above influenza vaccine against hospitalisation with community-acquired pneumonia (CAP) in the elderly.

Cold-adapted (ca) live attenuated influenza vaccines (LAIVs) have been introduced as alternatives to existing inactivated influenza vaccines. The influenza A components of the FDA-approved ca LAIVs (Flumist®; Medimmune) have common internal genes derived from the donor strain A/Ann Arbor/6/60 ca and surface genes derived from current wild-type (wt) epidemic strains. The aim of this thesis was to investigate determinants of immunogenicity for reassortants of A/Ann Arbor/6/60 ca, using a range of immunological assays, including recently developed MHC tetramer techniques. From the study, the extent of viral replication in the respiratory tract of mice, the primary site of inoculation, was a key factor in determining ca vaccine immunogenicity. Replication was shown to be influenced by both viral surface Ags and the host MHC. The H3 ca reassortants CR6, CR18, CR29 and CR6-35* exhibited greater replication efficiency (as determined by their PFU:HAU ratios) than the H1 ca reassortants CR35 and CR6-35. The H3 ca reassortant CR6 caused a 3.79% loss in body weight but no losses were observed for the H1 ca reassortant CR35 and the ca H2N2 donor strain A/Ann Arbor/6/60 ca. Higher HI responses were detected after 3 weeks in groups infected with the H3 ca reassortant CR6 (GMT 80) than with the H1 reassortant CR35 (GMT 10) and the H2 ca donor strain A/Ann Arbor/6/60 ca (GMT 13). Recently developed techniques were used to evaluate specific T-cell response to ca LAIVs. Fluorescent-labelled tetramer is the key reagent for use in tetramer-based flow cytometry assays. The NP366-374 peptide of influenza A viruses comprises an immunodominant epitope that is highly conserved between subtypes. Tetramers developed for A/PR/8/34 (H1N1) were able to detect NP-specific cytotoxic T lymphocytes (CTLs) induced by A/Ann Arbor /6/60 ca (H2N2). An attempt to prepare the A/Ann Arbor/6/60 ca-specific-NP-tetramer is described. H-2Db monomers were successfully refolded with the peptide, but only 20% were able to form tetramers through biotin-streptavidin linkage, resulting in a poor capacity to stain. By contrast, an IFN-γ ICC assay developed in parallel demonstrated that peptide NP366-374 was able to restimulate A/Ann Arbor/6/60 NP ca-specific CTLs and secrete IFN-γ when tested in vitro. Specific-B and T cell responses induced in the lungs in response to infection by ca reassortants exhibited great variability that was determined by the growth characteristics of different viruses. Type I (CTL) responses were induced by low yielding ca reassortants, such as CR35 (H1N1). Viruses with enhanced growth characteristics, such as CR6 (H3N2), produced higher Type II (HA-specific Ab) responses. In addition, host factors, such as MHC type, were found to play an important role in responses to the same viruses. Susceptible mouse strains, such as C57BL/6, showed higher CTL but lower serum Ab responses than more resistant strains, such as BALB/c. Throughout this PhD project, a fine balance between the humoral and CMI, local and systemic immune responses induced by ca LAIVs was demonstrated. The need to assess local immune responses, in addition to serum antibody levels, for the evaluation of vaccine efficacy was an important conclusion of the thesis.

The influenza virus, a member of the Orthomyxoviridae family, causes regular, large-scale morbidity and mortality in birds and humans and significant human suffering and economic loss. The primary aim of this study was to develop a novel influenza vaccine. Vaccines are an essential tool for the control of influenza because they increase resistance to infection, prevent illness and death and help to limit virus transmission to other birds and mammals, including humans. By reducing the environmental contamination of influenza virus in global poultry stocks, the risk of a new pandemic virus being generated by the human-avian link is diminished. Marek’s Disease is a common lymphoproliferative disease of poultry that is readily controlled worldwide using the live attenuated vaccine, CVI988. The Marek’s Disease Virus (MDV) CVI988 viral genome, available as a Bacterial Artificial Chromosome (BAC), forms viable infectious viral particles when transfected into Chicken Embryo Fibroblast (CEF) cells. Using BAC mutagenesis, two non-essential genes in the MDV CVI988 BAC (UL41 and US10), were identified and replaced by the low pathogenic influenza haemagglutinin 10 (H10) gene. These live recombinant MDV-H10 vectors will allow simultaneous vaccination against both pathogens. In addition, the non-essential genes were also replaced with GFP creating MDV-GFP constructs. Both genes were expressed initially using a CMV promoter, although this disrupted the MDV CVI988 BAC; a second promoter, PGK-1, proved more successful. A third MDV gene (UL50) was deleted, but severe attenuation prevented the incorporation of H10 into this open reading frame. Future work to test the MDV-HA constructs in vivo will be carried out in collaboration with the Istituto Zooprofilattico Sperimentale delle Venezie in Italy. In addition, development of MDV constructs containing multiple HA genes (H10 and H5) linked by the 2A polyprotein can be developed with the goal of establishing heterosubtypic immunity.

Influenza is a public health problem that causes serious illness and deaths all over the world. Vaccination has been shown to be the most effective mean to prevent infection. The primary component of influenza vaccine is the weakened strains. Vaccination triggers the immune system to develop antibodies against those strains whose viral surface glycoprotein hemagglutinin (HA) is similar to that of vaccine strains. However, influenza vaccine must be updated annually since the antigenic structure of HA is constantly mutation. Hemagglutination inhibition (HI) assay is a laboratory procedure frequently applied to evaluate the antigenic relationships of the influenza viruses. It enables the World Health Organization (WHO) to recommend appropriate updates on strains that will most likely be protective against the circulating influenza strains. However, HI assay is labour intensive and time-consuming since it requires several controls for standardization. We use two machine-learning methods, i.e. Artificial Neural Network (ANN) and Logistic Regression, and a Mixed-Integer Optimization Model to predict antigenic variety. The ANN generalizes the input data to patterns inherent in the data, and then uses these patterns to make predictions. The logistic regression model identifies and selects the amino acid positions, which contribute most significantly to antigenic difference. The output of the logistic regression model will be used to predict the antigenic variants based on the predicted probability. The Mixed-Integer Optimization Model is formulated to find hyperplanes that enable binary classification. The performances of our models are evaluated by cross validation.

Influenza is a public health problem that causes serious illness and deaths all over the world. Vaccination has been shown to be the most effective mean to prevent infection. The primary component of influenza vaccine is the weakened strains. Vaccination triggers the immune system to develop antibodies against those strains whose viral surface glycoprotein hemagglutinin (HA) is similar to that of vaccine strains. However, influenza vaccine must be updated annually since the antigenic structure of HA is constantly mutation. Hemagglutination inhibition (HI) assay is a laboratory procedure frequently applied to evaluate the antigenic relationships of the influenza viruses. It enables the World Health Organization (WHO) to recommend appropriate updates on strains that will most likely be protective against the circulating influenza strains. However, HI assay is labour intensive and time-consuming since it requires several controls for standardization. We use two machine-learning methods, i.e. Artificial Neural Network (ANN) and Logistic Regression, and a Mixed-Integer Optimization Model to predict antigenic variety. The ANN generalizes the input data to patterns inherent in the data, and then uses these patterns to make predictions. The logistic regression model identifies and selects the amino acid positions, which contribute most significantly to antigenic difference. The output of the logistic regression model will be used to predict the antigenic variants based on the predicted probability. The Mixed-Integer Optimization Model is formulated to find hyperplanes that enable binary classification. The performances of our models are evaluated by cross validation.

Influenza is an important respiratory pathogen that infects several million people each year. Currently available flu vaccines have to be updated regularly in order to be effective as the virus changes its composition by antigenic drift and shift. Most of the antibody response generated by these vaccines is strain specific as it is directed against the head domain (HA1) of HA. The HA2 subunit of hemagglutinin is highly conserved and immunogens designed from this subunit are likely to provide protection against multiple strains of the virus. However, expression of HA2 alone in the absence of HA1 resulted in a protein that took up the low pH conformation of HA. Our goal was to design immunogens from HA2 that would fold into the neutral pH form. Sequence analysis of a large number of HA protein sequences was carried out to identify conserved and exposed regions on HA. Several peptide and protein constructs were designed from the stem region of HA. These proteins were expressed in bacteria and purified proteins were used to immunize mice. Immunized mice were challenged with a lethal dose of virus to test for efficacy of the immunogen. Using this approach, stem domain constructs of HA were successfully designed and shown to take up the neutral pH form. These immunogens were also shown to be capable of providing broad range protection. Residues involved in the low pH induced conformational change of HA were identified from studies on HA2 derived peptides.