Bakgrund: Vaccin är sjukvårdens viktigaste, mest kostnadseffektiva åtgärd som räddar två till tre miljoner liv per år världen över. Hög vaccintäckning skyddar inte bara individerna utan minskar spridningen av sjukdomar i samhället. Trots detta finns det personer som tvekar på dess effektivitet, säkerhet och nödvändighet. Dessa personer väljer att avstå från att vaccinera sina barn, vilket innebär en risk för individen och samhället. Syfte: Syftet var att beskriva vilka faktorer som gör föräldrar tveksamma till att vaccinera sina barn enligt deras nationella vaccinationsprogram. Metod: Litteraturstudie baserad på tio kvalitativa artiklar publicerade mellan år 2012 och 2019. Datainsamlingen utfördes i databasen PubMed och en sekundärsökning gjordes för att få ett så täckande resultat som möjligt. Den teoretiska referensramen för den här studien grundades på Leiningers transkulturella omvårdnadsteori. Resultat: Resultatet presenteras i fem olika teman: Allvarliga biverkningar och farliga tillsatser, Brist på information, Hälsosam livsstil och naturlig immunisering, Förtroende för myndigheter och Bristande kunskap om sjukdomar. Majoriteten av deltagarna var rädda för att vaccinet kunde skada deras friska barn. Det fanns även en misstanke om att sjukdomarna som vaccin skyddar mot inte är speciellt farliga och att myndigheter som rekommenderar vaccin har finansiellt motiverade avsikter. Hälsosamma levnadsvanor och naturlig uppbyggnad av immunförsvaret ansågs tillräckligt för att skydda ett barn genom livet. Slutsats: De huvudsakliga faktorerna till varför föräldrar tvekar inför att vaccinera sina barn grundar sig i bristande förståelse för vaccin och sjukdomarna det skyddar mot. Genom att skapa sig en förståelse av alla bakomliggande faktorer som påverkar vaccinets förtroende kan varje land skräddarsy insatser som ökar vaccintäckningen. / Background: Vaccine is the most important, cost effective healthcare action that saves two-three million lives each year all over the world. High coverage of vaccine not only protects the individuals but reduces the spread of diseases in the community. Still, there are people who doubt its effectiveness, safety and necessity. These people choose to refrain from getting their children vaccinated, which puts the individual and the society at risk. Purpose: The purpose was to describe what factors make parents hesitant to vaccinate their children according to their national vaccination programme. Method: Literature study based on ten qualitative articles published between 2012 and 2019. The data collection was carried out in the PubMed database and a secondary search was done to obtain as comprehensive result as possible. The theoretical framework of reference for this study was based on Leininger's transcultural nursing theory. Results: The results are presented in five different themes: Serious side effects and dangerous additives, Lack of information, Healthy lifestyle and natural immunization, Trust in authorities and Lack of knowledge about diseases. The majority of participants were afraid that the vaccine could harm their healthy children. There was also a suspicion that what the diseases vaccines protect against are not particularly dangerous and that the authorities recommending the vaccines have financially motivated intentions. Healthy living habits and natural enhancement of the immune system were considered sufficient to protect a child through life. Conclusion: The main factors to why parents hesitate to vaccinate their children are based on a lack of understanding about the vaccines and the diseases it protects against. By creating an understanding of all the factors affecting the confidence in vaccine, each country can tailor actions that increase vaccine coverage.

Measles is a potentially deadly illness that has been declared no longer endemic in the United States of America since 2000.1 However, in the past few years, imported cases of the measles have continued to cause hospitalization and deaths among those citizens who remain unvaccinated, or have waning immunity, against measles, especially children. The Measles, Mumps and Rubella (MMR) vaccine has been available since 1963 and is routinely given to children in the first two years of life.1 Endemic cases of measles are increasing each year, specifically in undervaccinated communities. In 2018-2019, there was an outbreak of measles in the Williamsburg neighborhood of Brooklyn, New York. Investigating the knowledge, attitudes and opinions on the measles virus and the MMR vaccine in the Williamsburg neighborhood may facilitate discussions that could increase the vaccination rate among its population, as well as elucidate more effective strategies for vaccination in the future. Comparing attitudes from the Williamsburg neighborhood with a population across the Hudson River, in the East Village, which has previously had higher rates of vaccination, could shed light on how to target and tailor vaccination campaigns to different populations in New York City moving forward.2–4

Introduction: Mortality in cancer has declined during recent years due to more efficient cancer treatments. Some of the novel immunotherapies against cancer under development has a risk of lacking regulatory guidance for the approval, such as neoantigen-based therapeutic vaccines. Aim: The purpose of the degree project is to evaluate the potential process of approval of neoantigen based vaccines from a regulatory perspective. Methods: The method used to gather data in the study is through qualitative interviews, regulatory documents, guidelines and data from current trials. Results: The results indicate that during the preclinical phase, neoantigen vaccines can receive warrants of a case-by-case approach leading to a more optimized development pathway. During clinical trials, the trial design could consist of master protocols, singlearm trials, comparative trials and adaptive trials where the control group may use the standard of care or historical controls. The indication in the trials should be cancer types with a high tumor mutational burden, low mortality rate, and high medical need. The biomarkers should evaluate immune and tumor response. Endpoints in early trials should evaluate safety and efficacy, and the tumor and immune response in pivotal trials. Neoantigen vaccines can use several incentives during the development and can be approved through conventional or conditional approval. Finally, the study suggests that it is yet too early for the agencies to have established any guidelines. However, advices from regulatory agencies can guide developers towards regulatory approval. Conclusion: This study shows that different study designs and various incentives can be used for the regulatory approval of individualized neoantigen based vaccines. Further guidelines need to be developed to enhance future development.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24139号 / 医博第4879号 / 新制||医||1060(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 森信 暁雄, 教授 上野 英樹, 教授 金子 新 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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<p>  </p> <p>The study presented within demonstrates that Nano-11, a plant-derived nanoparticle adjuvant, can be utilized in conjunction with innate immune stimulators, including the TLR3 agonist poly(I:C) and the STING agonist cyclic-di-AMP, to provoke enhanced immune responses when administered through intradermal vaccines. The study demonstrated that the utilization of a combination adjuvant consisting of Nano-11 and a synthetic STING agonist, ADU-S100, in intradermal vaccination exhibited dose-sparing characteristics and resulted in enhanced immunity in both mice and pigs when compared to intramuscular immunization. The utilization of Nano-11-based adjuvant technology has demonstrated both prophylactic and therapeutic efficacy in mouse models of lymphoma and melanoma. The proposed adjuvant platform for intradermal vaccines, which is based on Nano-11, aims to enhance the accessibility of vaccines for the purposes of controlling infectious diseases and cancers.</p>

Introduction The discovery and continued development of vaccines is arguably one of the most important innovations in human history. Vaccination greatly reduces the worldwide incidence and transmission of diseases, preventing permanent injury and premature death. Mass vaccination campaigns have led to the eradication or partial eradication of severe infectious such as smallpox and polio, have reduced childhood mortality, and has led to an overall increase in average health in the human population globally. Despite the documented benefits of vaccination, vaccine hesitancy is increasing, and the uptake of some vaccines is low. Vaccines have been so successful at preventing disease that portions of the population are now more afraid of the possible side-effects of vaccines then they are of the serious symptoms and maladies that vaccines prevent. Vaccine hesitancy is a serious concern for the global medical community. The incidence of infectious disease is inversely proportional to vaccine uptake; as fewer people are vaccinated against preventable diseases, the frequency at which people get sick increases. A reduction in vaccination rates due to vaccine hesitancy reduces herd immunity, which increases the risk for the whole population, especially immunocompromised individuals who are unable to receive vaccines. Vaccines that protect against high-risk strains of Human Papillomavirus (HPV) have recently been developed and released to the worldwide population. High-risk HPV strains can cause persistent infection and various cancers. Although HPV vaccines have been extensively tested and are recommended by the Centers for Disease Control and Prevention and the World Health Organization, uptake among some demographics is low. Understanding what factors impact HPV vaccine hesitancy can guide the design of effective interventions which can increase vaccine uptake. High HPV uptake will lead to a reduction of HPV associated cancers and reduce the transmission of high-risk subtypes. Research Significance Vaccine hesitancy is a growing challenge for the medical community and could potentially put global health at risk by undermining 200 years of progress towards eliminating infectious diseases. A better understanding of what factors impact vaccine hesitancy allows public health professionals to design better policies and interventions policies and helps primary care providers better address concerns the concerns of their patients. Better understanding of the factors which cause vaccine hesitance can be used to tailor education about vaccines. This leads to higher vaccine uptake and better community health overall. Methodology Electronically distributed surveys and statistical analysis were the primary tools used in this research. Surveys were used to generate data from a sample population, including: demographic factors, attitudes towards vaccination, and intent to vaccinate against HPV. Barriers to HPV vaccine uptake and factors that impact HPV vaccine acceptance were identified through statistical analysis, including confirmatory factor analysis, structural equation modeling, regression and univariate analysis. Findings We found that general attitudes toward vaccination had the greatest impact on the intent of parents to vaccinate their children against HPV. Parents who view vaccination positively intend to vaccinate their children against HPV or have already vaccinated their children against HPV. Parents who are somewhat unsure about vaccines are more hesitant about vaccinating their children against HPV. Knowledge about HPV increases intent to vaccinate. We found that traditionally religious parents who felt that religious adherence provided some protection against HPV were more hesitant about HPV vaccinations. We found that both a religious-focused intervention and an education-focused interventions increased parental intent to vaccinate more than a control intervention. Our study of Utah residents confirmed our earlier findings that general attitudes toward vaccination had the greatest impact on the intent of parents to vaccinate their children against HPV. Our study also confirmed that knowledge about HPV increases intent to vaccinate. We found that high religious practice negatively impacts parental intent to vaccinate. Cautious sexual attitudes also negatively impact intent to vaccinate against HPV. High religious practice is correlated with cautious sexual attitudes which explains the negative impact of high religious practice on intent to vaccinate. The findings of this research work will be used to inform future religious and educational based interventions in Utah and beyond.

Objective: Little is known about the parental perception of usage and delivery of Vaccine Information Statements (VISs), the timing of VIS delivery, parent opportunity to read VISs, and time for discussing content of VISs with providers. Parental reports of dissemination and use of VISs are explored in this study, including parental use, experience, and perceptions. Method: Data for this pilot cross-sectional descriptive study were collected via an online survey. The instrument consisted of 21questions including five demographic questions, 11 questions about VIS distribution, four questions about parental use and understanding of VISs, and one open-ended question about finding information about immunizations (see appendix A). The questionnaire was available in both English and Spanish. Results: Responses from 130 parents in one school district were used for analysis. Most participants (67.7%) reported getting vaccine information from a pediatric healthcare provider. A large majority of participants (71.5%) said VISs were included as part of the vaccination process and that they received a paper copy (64.6%). About a third of participants (37.7%) said they read some or all of the VIS before their child was vaccinated and over half (59.3%) said they read some or all of the VIS after their child was vaccinated. Discussion: While it is promising that many parents reported receiving the federally mandated vaccine information, over a quarter of parents reported they did not receive a VIS. Similar to findings in the literature, a majority of parents read all or part of the VIS after an immunization appointment. Limited time to read and understand the information on the VIS before an immunization was administered may lead to limited parental understanding. Although some parents reported struggling to understand VISs, more than half of the parents in our study said that VISs were helpful and would read another in the future. Nursing Implications: Without appropriate use of VISs and other vaccine education material, providers miss the opportunity to educate parents on the risks and benefits of vaccinating their children. Conclusion: Since their implementation in 1986, there has been little research on VIS use for vaccine education and parental perception. Providers must be aware of literacy levels and vaccine attitudes and create appropriate opportunities for parents to read and learn about vaccines. VISs are a valuable tool to educate patients and parents on the benefits and risks of vaccines. Improvements are needed to improve the clarity of the VIS messaging and dissemination practices.

HIV and Tuberculosis (TB) co-infection place an immense burden on health care systems as they act in synergy to worsen disease prognoses. TB is the most common cause of death in people living with HIV (PLWH) and in turn, HIV is the most significant risk factor for progressing from latent to active TB disease. While HIV and TB are endemic in sub-Saharan Africa, they also disproportionately affect marginalized populations in Canada. Unfortunately, the only licensed TB vaccine, BCG, does not protect from adult pulmonary TB and is not recommended for PLWH. Thus, the development of novel TB vaccines, which are safe and effective in PLWH, remains an urgent global necessity. We have found that humanized mice (hu-mice) are ideal models to research this as they can be successfully infected with HIV, TB and HIV/TB and recapitulate human disease pathology. A next-generation respiratory mucosal (RM) trivalent chimpanzee adenoviral-vectored vaccine (Tri:ChAd68) was developed and tested in our naïve and HIV-infected hu-mice. When immunizing naïve hu-mice, a trend of increased M.tb-specific CD4+ T cells producing IFNγ and TNFα in the lungs and spleen was observed. After subsequent M.tb infection, the vaccinated naïve hu-mice also exhibited significantly reduced lung mycobacterial burden, tissue dissemination and lung pathology. We then investigated the vaccine immunogenicity and ability to protect from TB in the context of HIV. Our immunized HIV-infected hu-mice were also able to produce M.tb-specific T cells and when challenged with M.tb, we observed a decreased trend in mycobacterial load in the lungs, indicating that the vaccine may be able to offer protection against TB when a prior HIV infection is present. These findings demonstrate the protective potential of the RM Tri:ChAd68 vaccine against TB disease for PLWH. In the future, we will test this vaccine in antiretroviral treated HIV-infected hu-mice to increase clinical significance. / Thesis / Master of Science in Medical Sciences (MSMS) / HIV and TB are major diseases that can occur together, severely worsening patients’ health and challenging global healthcare systems. The current TB vaccine, BCG, isn’t ideal for people living with HIV (PLWH), causing this vulnerable population to be at greater risk of getting TB infection. Therefore, developing a new TB vaccine that is safe and effective in PLWH is an urgent global issue. We used humanized mice that develop human immune cells to test a novel TB vaccine delivered to the lungs (Tri:ChAd68) to see if it could protect against TB and overcome immune challenges from HIV. We saw increased immune responses and lower TB infection in our vaccinated humanized mice and the vaccine appeared to also be beneficial in the mice that had prior HIV infection. This suggests the Tri:ChAd68 vaccine may be able to offer protection against TB in PLWH; however, more studies are needed to conclude this.

At the beginning of 2020, the SARS-CoV-2 virus, known more commonly as COVID-19, created a pandemic. To slow its spread, healthcare workers were heavily encouraged to vaccinate themselves. However, nurses have been less likely to be vaccinated against COVID-19 than physicians. Four common themes have been associated with vaccine hesitancy among nurses, namely certain demographic variables (e.g., younger age and female sex), fears of the vaccine, conspiracy theories and news sources, and medical and psychological histories that pertain to receiving the COVID-19 vaccine. Thus, this study aimed to identify whether these factors apply to Florida nurses' decisions to get vaccinated after the height of the pandemic. To approach this problem, sixty-five participants were surveyed through a Qualtrics cross-sectional questionnaire. The results revealed that approximately 18.5% of participants were not vaccinated. Trends in the data revealed that older age and a postgraduate education level were associated with receiving the vaccine. Non-vaccinated participants had less confidence in the vaccine's ability to reduce the risk of hospitalization, death, and infection, and they had a stronger fear of side effects and the vaccine's rapid development. Several vaccinated and non-vaccinated participants also believed vaccine conspiracy theories, such as that vaccine safety data is falsified. Many non-vaccinated nurses also received SARS-CoV-2 information from social media or their patients, whereas many vaccinated nurses received information from government news sources or physicians. Non-vaccinated nurses also tended to have more discomfort towards hypodermic injections than vaccinated nurses. These conclusions are generalizable to the nurses of this study and may not be generalizable to all nurses. However, because nurses are on the frontlines of the healthcare field and have an essential role in informing the public about health, the results of this study can help inform vaccine education interventions should a future pandemic occur.