Cancer vaccines can fail despite the induction of large numbers of CD8+ T cells. Two categories of memory CD8+ T cells have been defined; central memory (TCM, IL-7RαhighCD44highCD62Lhigh) and effector memory (TEM, IL-7RαhighCD44highCD62Llow). It is clear that the memory phenotype of CD8+ T cells can affect vaccine potential; however methods to augment a beneficial phenotype are not clear. I have compared three vaccine delivery systems: Listeria monocytogenes, Salmonella enterica serovar Typhimurium and the particulate liposomal adjuvant, archaeosomes, for their efficacy to protect against murine melanoma. My study revealed that the anti-tumour response is strongly influenced by the kinetics, phenotype, and lymph node homing potential of CD8+ T cells. Listeria monocytogenes-ovalbumin (LM-OVA) induced TCM cells were adept at long lasting protection against B16-OVA melanoma due to their increased homeostatic and antigen-induced proliferation, interleukin-2 production, and ability to extravasate into tumour draining lymph nodes. Conversely, although Salmonella Typhimurium-ovalbumin (ST-OVA) induced TEM, produced IFN-γ, and killed target cells, this was insufficient for long-term tumour protection. Selectin-ligand engagements of TCM cells influenced their homing potential and efficacy against murine melanoma. Fucosyltransferase deficient (FtDKO) mice, lacking functional selectin ligands, were vaccinated with LM-OVA; despite the activation of cytotoxic CD8+ T cells, there was a reduced protection against murine melanoma compared to wild-type. FtDKO CD8+ T cells exhibited reduced extravasation into FtDKO lymph nodes compared to wild-type. Additionally, fewer FtDKO CD8+ T cells compared to wild-type migrated into tumour sites. Archaeosome vaccination was used to compare the influence of CD8+ T cell quantity versus phenotype. Single or multiple therapeutic vaccinations with archaeosome-OVA yielded transient melanoma tumour protection, despite an increased frequency of circulating and tumour infiltrating CD8+ T cells. This correlated with increased expression of Program death receptor-1 (PD-1) on CD8+ T cells and induction of regulatory T cells. Prophylactic archaeosome-OVA vaccination resulted in a maximal frequency of antigen-specific CD8+ T cells of ~50-60 % with just three injections, and ~50 % of the mice were of mice were afforded long-term tumour protection (> 90 days). Overall, my study shows that the choice of vaccine adjuvant and/or vector can profoundly influence CD8+ T cell quality and cancer vaccine efficacy.

Background: An estimated 50,000 adults in the United States (U.S.) die each year from one of 10 vaccine preventable diseases. For those who survive vaccine preventable infections, health care costs and loss of income become more significant. While children in the U.S. aged 0-2 exhibit vaccine prevalence rates of almost 90%, some adult vaccine prevalence rates in the U.S. population are reported to be nearly 30-40% less than the goals set forth by Healthy People 2010. The purpose of this study was to examine the associations between socio-demographic characteristics of U.S. adults and adult vaccination prevalence for pneumococcal, hepatitis A, hepatitis B, tetanus, and pertussis. Methods: Data from the 2008 National Health Interview Survey were assessed examining various health indicators and characteristics of non-institutionalized adults and children. The sample was restricted to adults ≥18 years of age. Odds ratios were calculated and multivariate logistic regression was also conducted. P-values of Results: There were 21781 total observations; 19.3% received the pneumococcal vaccine, 9.4% received the hepatitis A vaccine, 27.2% received the hepatitis B vaccine, 55.1% received the tetanus vaccine, and 15.2% received the pertussis vaccine. Of the socio-demographic characteristics examined, age, health insurance, marital status, and education were significant for either all five or at least four of the vaccines included in this study. As one might expect those who reported health insurance and those who had a higher level of education usually had a higher likelihood of vaccine receipt as compared to those without health insurance and those with less than a high school education. Age associations varied due to age-related recommendations for certain vaccines such as pneumococcal (recommended for adults ≥65). Compared to the married population (referent), marital status results varied, but for reasons unclear. Whites, the referent group, were the most likely to be vaccinated as compared to Blacks, Hispanics/Latinos, and Asians. Hispanics/Latinos typically had the lowest likelihood of vaccination in this examination. Conclusions: This study further explores the impact of socio-demographic disparities on vaccination status and adds new information to the literature regarding adult vaccination rates for preventable diseases. While research exists related to strengthening interventions such as patient reminder systems, those who do not see the same health care providers on a regular basis remain at risk for lower vaccination prevalence. It is important to better understand the role of social determinants of health, specifically in terms of vaccinations. Future research is needed to further characterize the association of socio-demographic factors with receipt of optional vaccines in adults.

Group A streptococcus (GAS) is an important pathogen that produces a wide spectrum of suppurative infections and autoimmune sequelae in humans, ranging from less complex pharyngitis, impedigo to more severe manifestations such as necrotizing fasciitis, toxic shock syndrome, rheumatic fever and glomerulonephritis. The worldwide burden of GAS infections and sequelae is considerable, but an immunization program that defends against the hyper-variable GAS is missing. The streptococcal hemoprotein receptor (Shr), is an iron-regulated protein involved in heme acquisition. An unspecified region in the amino terminus of Shr mediates the interactions with hemoglobin and two protein modules named NEAT1 and NEAT2 bind heme. In this study, we analyzed the molecular structure and function of Shr, investigated its antigenic properties and role in GAS disease production. We demonstrated that Shr is a new type of GAS adhesin that contributes to the pathogen interactions with extracellular matrix (ECM) proteins. Shr enabled bacterial adherence to host cells and was important for GAS virulence in vivo. Immunizations with Shr protein by intraperitoneal or intranasal administration conferred resistance to systemic GAS challenge in mice. Shr antiserum allowed bacterial opsonization and defended against GAS diseases in a murine model for passive vaccination. Studies with isolated Shr domains localized ECM-binding to the NEAT domains and showed that most of the protein is exposed on the bacterial surface. In addition, Shr N-terminal region and both of the NEAT modules elicited strong antibody response in rabbits. In conclusion, Shr is a protective antigen that contributes to GAS pathogenesis by facilitating both heme uptake and bacterial adherence. Since Shr is conserved among GAS strains and other pyogenic streptococci, this study demonstrates that Shr may be used to develop a vaccine against GAS strains and related pathogens.

Bakgrund: Sedan januari 2010 ingår vaccin mot humant papillomvirus i det svenska barnvaccinationsprogrammet. Beslutet att vaccinera eller inte vaccinera sina barn kan vara svårt för föräldrar. Syfte: Var att beskriva föräldrars kunskap om och attityd till vaccin mot humant papillomvirus och hur det inverkar på deras beslut att vaccinera sina barn. Design: Mixed-methods research integrated design. Metod: Beskrivande litteraturstudie. En systematisk sökning gjordes i databaserna CINAHL och PubMed och 12 artiklar identifierades. Artiklarna hade kvantitativ och kvalitativ ansats. Resultat: Föräldrar var positiva till HPV-vaccin. Många föräldrar hade liten kunskap om vaccinet och upplevde att de inte hade tillräckligt med information. Det fanns en oro för vaccinets säkerhet och biverkningar. Många fick information från media men den föredragna informationskällan var vårdgivare. De som fått information från vården var mer positiva till vaccinet. Föräldrar ansåg att den rekommenderade åldern för vaccinet var för låg och det fanns en rädsla att en vaccination skulle påverka dotterns sexuella beteende. Bland de föräldrar som valde att vaccinera var den oron mindre. Sociala normer och religion påverkade föräldrarna i besluten kring vaccination. Lägre utbildning var en prediktor för att välja att vaccinera. Egen eller anhörigas erfarenhet av cellförändringar eller cervixcancer påverkade också intentionen att vaccinera.   Sökord: MeSH-termerna accept*, attitudes, behavior, beliefs, decision, HPV-vaccine, intent*, knowledge, parents. / Background: Since of January 2010 vaccine against human papillomavirus (HPV) is a part of the Swedish child vaccination program. The decision to vaccinate can be difficult for the parents to make. Purpose: The purpose of the study was to describe parental knowledge and attitude towards vaccine against human papillomavirus and how that influenced their decision to vaccinate their children. Design: Mixed methods research with integrated design. Method: A descriptive literature review. A systematic search was performed in the databases PubMed and CINAHL and 12 studies were identified. The studies had quantitative and qualitative design. Results: Parents were positive towards the HPV-vaccine. Many parents lacked knowledge and felt they didn´t have enough information about the vaccine. There was concern about the safety and side effect. Many got their information from media but the preferred source of information was caregivers. Parents who had gotten information from caregivers were more positive towards the vaccine. The recommended age for vaccination was considered too low and there was concern that a vaccination would have an effect on their daughter’s sexual behavior. Among the parents who had made the choice to vaccinate that concern was lower. Social norms and religion affected the parents in their decision to vaccinate. Lower education was a predictor in the decision to vaccinate. Experience of abnormal pap-smears or cervicularcancer also affected the intention to vaccinate.   Search words: MeSH-therms accept*, attitudes, behavior, beliefs, decision, HPV-vaccine, intent*, knowledge, parents.

This thesis describes the West Nile virus (WNV) epidemic in horses by exploring all aspects: sub-clinical infection, development of clinical disease and case fatality. All of the collected data were then compiled to create predictive risk maps of WNV infection for the province of Saskatchewan. <p>During the 2003 season, 133 clinical cases were documented with laboratory testing. Week of onset of clinical signs, gender, and coat color were significant predictors of whether the horse died or was euthanized due to severity of clinical signs. Studies of the serological response to vaccination and natural infection were examined to interpret the lab results from over 1100 samples taken from approximately 875 horses in 2003. A serologic study involving 212 horses on 20 farms determined the prevalence of sub-clinical infection (55.7% (95%CI, 44.9% to 65.8%)) and identified risk factors for infection. The study found risk of infection was highest in the Grasslands ecoregions compared to the Boreal Transition ecoregion. A case control study looked at risk factors for development of clinical disease. The study followed 23 case farms and control farms with a total of 300 horses sampled. This was the first field study to show that vaccination was efficacious in preventing the development of clinical signs. <p>The inclusion of horse surveillance data in the Saskatchewan Health WNV Integrated Surveillance Initiative was useful; however, it was discontinued due to time constraints, logistics, and declining monetary resources. <p>Since West Nile Virus is a mosquito-borne disease it is highly influenced by environmental changes, spatially and temporally. Discriminant analyses were used to partition Saskatchewan rural municipalities (RM) into categories of risk of infection with WNV based on acquired horse data and different environmental and meteorological data derived from both satellites or climate stations. The result was the creation of yearly predictive risk maps defining low to high risk of infection with WNV for each RM. <p>The 2003 epidemic provided a novel opportunity to study an important zoonotic disease emerging in a new environment. The information gathered will further the knowledge base upon which decisions for prevention of infection and clinical disease are made.

As respiratory syncytial virus (RSV) is a respiratory pathogen that causes significant morbidity and mortality in infants, there has always been great interest in the development of a vaccine. In the 1960s, children were immunized with formalin-inactivated (FI)-RSV vaccines. Not only did these vaccines fail to prevent infection, but in most cases they resulted in enhanced disease upon subsequent exposure to the virus. In the intervening years, studies in mice have led to the hypothesis that the enhanced disease is due to an aberrant Th2-biased immune response. Thus, we hypothesized that formulating FI-RSV vaccines with a Th1 promoting adjuvant, such as CpG oligoeoxynucleotides (ODN), would result in the induction of protective immunity against RSV without risk of deleterious effects. We observed in calves that parenterally delivered FI-bovine RSV (BRSV) formulated with CpG ODN resulted in a shift towards a Th1-biased or more balanced immune response that was protective against BRSV.<p> As RSV infects the lung mucosa, vaccines that induce mucosal immunity are desirable. Parenterally delivered vaccines typically induce systemic immunity with low mucosal immune response levels, whereas mucosally delivered vaccines induce systemic and mucosal immunity. However, upon mucosal delivery there is an increased chance of vaccine components being degraded or washed away prior to the induction of immunity. Thus, we added polyphosphazenes (PP) to our mucosal vaccine formulations. PP are synthetic polymers that form non-covalent complexes with other vaccine components, increasing their stability. Intranasally delivered FI-BRSV co-formulated with CpG ODN and PP performed better than FI-BRSV alone, or FI-BRSV formulated with either adjuvant individually, in terms of inducing protective immunity against BRSV in mice. Furthermore, mice that received intranasally-delivered FI-BRSV or BRSV F protein co-formulated with CpG ODN and PP developed higher levels of immunity and protection than mice that received parenterally delivered vaccines. Because of the similarities between BRSV and HRSV, co-formulation of intranasally delivered HRSV vaccines with CpG ODN and PP could prove important in the development of a safe vaccine against HRSV in humans.

The Shiga-like toxins have DNA sequence homology to the toxins accountable for the dysentery brought about by the Shigella species. <i>Escherichia coli</i> which encode and produce shiga-like toxins are referred to as shiga toxin-producing E. coli (STEC). Upon infection with STEC, humans may develop a variety of clinical symptoms ranging in severity from bloody diarrhea to life threatening hemolytic uremic syndrome (HUS). Hemolytic uremic syndrome is the most fatal disease manifestation upon STEC infection for humans and has been documented to occur in up to 20% of patients upon STEC infection [29]. The Shiga toxins (Shiga toxin 1 and 2) are regarded as the principal virulence factor of STEC and are responsible for the clinical manifestations during HUS in humans [49].<p> Cattle are the primary non-human reservoir for STEC and therefore represent an attractive target for pre-slaughter intervention as a means to reduce human infections. To date, vaccination with secreted proteins including Shiga toxin 2 (Stx2), has reduced the numbers of bacteria shed in feces [3]. Even though published data exists supporting vaccination in cattle as a means to reduce STEC, commercially available vaccines are not being used by farms and STEC remain a significant zoonotic pathogen of humans causing disease and death. To further our knowledge about STEC pathogenesis in cattle, we examined the effect of Shiga toxin 2 on bovine immune responses. Bovine lymphocyte function was determined in the presence of Shiga toxin 2 and the magnitude of bovine immunological responses was measure after immunization with Shiga toxin 2. In general, results suggest that Shiga toxin 2 downregulates bovine immune responses suggesting vaccination with effector molecules that exclude Shiga toxin 2 may induce a better immunological response and improve vaccine efficacy.<p> To examine the possibility that Stx2 modulates bovine immune responses, we investigated lymphocyte function in the presence of Stx2. Menge et al [70] have reported that bovine lymphocytes express the Stx receptor and that Shiga toxin 1 inhibits lymphocyte proliferation in vitro. We isolated two populations of lymphocytes, peripheral blood mononuclear cells (PBMCs) and ileal Peyers patch lymphocytes (IPPL) and compared lymphocyte function in the presence and absence of Stx2. We found that Stx2 did not affect IPPL viability in vitro but did inhibit IPPL proliferation after 12 hours of incubation <i>in vitro</i>. In contrast, no altered PBMC function could be observed in the presence of Stx2. These results suggest that receptor-bound Stx2 may inhibit IPPL proliferation and that the two populations of lymphocytes isolated are unique and distinct from each other in their response to Stx2.<p> To determine the effect of Stx2 on bovine immune responses during STEC infection, a bovine ileal ligated loop model was employed. Ligated loops were inoculated with either a Stx2+ STEC strain or an isogenic Stx2- STEC strain. After 24 hours, IPPL populations were isolated from each ligated loop and immunophenotyped. The results indicated a significantly reduced CD4+ T cell population in the presence of Stx2. No differences in the levels of IFNá, TNFá, IL12 or IFNã could be detected between groups. These results suggest that Stx2 modulates bovine immune responses but not as a result of increased production of these cytokines. To extend this finding, we determined the effect of Stx2 on bovine immune responses during active immunization by using ELISA to measure serological responses in the presence and absence of Stx2. Serological responses to secreted proteins, as well as a co-administered antigen (hen egg lysozyme), were significantly reduced in the groups of cattle that were immunized with either purified Stx2 or secreted protein preparations isolated from STEC compared to groups vaccinated with antigens which did not contain the toxin. Bovine proliferative responses were also measured and the results indicated significantly reduced proliferation in the groups vaccinated with the formulations containing Stx2. Therefore, based on these results, we conclude that Stx2 downregulates bovine immune responses and thus may contribute to the colonization and persistence of cattle by STEC.

Resandet mellan länder ökar allt mer och många resor går från rikare till fattigare länder i tropiska och subtropiska områden. De resande möter ett annat panorama av sjukdomar än i hemlandet och det vanligaste hälsoproblemet bland resenärer är turistdiarré. Inför resan söker många råd på en vaccinationsmottagning. Råd ges bland annat kring kost och vaccin för att förhindra turistdiarré. Syftet med studien var att undersöka det vetenskapliga underlaget för att sjuksköterskor skall kunna ge evidensbaserade råd kring kosthållning och vaccination för att undvika turistdiarré. Sökningar i framför allt PubMed och Cinahl utmynnade i 15 kvantitativa artiklar som kom att utgöra material till litteraturstudiens resultat. Litteraturen gav motstridiga svar på frågan om kostrådens betydelse för att förhindra turistdiarré. Resultaten antydde att risken för att insjukna varierade med ålder, resans duration och destination. Resultatet visade vidare att det finns ett vaccin med viss effekt mot turistdiarré. Färre vaccinerade insjuknade och de som insjuknade var sjuka kortare tid. Vaccinet skyddade framför allt mot svårare diarrésjukdom. De studier som fanns gjorda på området var få och i många fall relativt gamla. Fler studier behövs för att säkrare slutsatser skall kunna dras som underlag för individuellt anpassade evidensbaserade råd. / Travel between countries continues to increase and many trips go from richer to poorer countries in tropical and subtropical areas. Travellers meet a different spectrum of diseases than in their home countries and the most common health problem among travellers is travellers´diarrhoea. It is common among travellers to seek advice at a travel clinic prior                                         to the trip. Advice is given on, among other things,                                                          diet and vaccine to prevent travellers´ diarrhoea. The aim of this literature study was to investigate the evidence base to enable nurses to provide evidence based advice on diet and vaccine to prevent travellers´ diarrhoea. The search for articles in mainly PubMed and Cinahl lead to 15 quantitative articles, which constituted material for the result of the literature study. The literature gave contradictory answers to the question of the significance of dietary advice. The results indicated that the risk for travellers´ diarrhoea varied with age, duration of the trip and destination. The results further showed that there is a vaccine with some effect against travellers´ diarrhoea. There was a lower incidence rate among the vaccinated and the ones who did contract travellers´ diarrhoea were ill during a shorter period of time. The vaccine protected mainly against more severe diarrhoea. The studies carried out on the area were few and in many cases relatively old. More studies are needed to enable assertive conclusions as material for individually suited evidence based advice.

Pasteurella multocida serotype A:3 is a gram-negative bacterial pathogen which is one of the causative agents of shipping fever in cattle. In this study, ompH and two fragments of plpE gene (plpEN and plpEC) were cloned from the genomic DNA of P. multocida P-1062 (ATCC 15743, serotype A:3) and plpEN-ompH and plpEC-ompH fusions were constructed. In vitro expression of the genes was shown in HEK-293 cells. Later, full-length plpE gene was cloned and the recombinant proteins were expressed in E. coli and purified. Three DNA vaccine formulations, namely pCMV-ompH, pCMV-plpEN-ompH and pCMV-plpEC-ompH and five recombinant protein based vaccines, PlpEN-OmpH, PlpEC-OmpH, OmpH, PlpEC and PlpE were generated. Recombinant proteins were formulated with at least one of the adjuvants: alum, CpG, alum-CpG, oil based and oil based-CpG. BALB/c mice were immunized with these vaccine formulations and their sera were used for the evaluation of antibody and serum IFN-&gamma / titers. Protective capacities of the vaccines were also evaluated via challenge of mice with 10 LD50 of P. multocida A:3. DNA vaccines induced immune responses, but did not provide protection. All protein vaccine formulations increased antibody levels and CpG containing formulations enhanced serum IFN-&gamma / titers. 100 &micro / g of PlpEC-OmpH protein adsorbed on alum adjuvant conferred 40% protection while no protection was obtained with PlpEN-OmpH. Next, the effects of CpG, or its alum and oil based combinations as adjuvants were investigated on PlpEC-OmpH mediated protection. The vaccine formulation composed of PlpEC-OmpH and oil based-CpG adjuvant conferred 100% protection. Finally, the mice were vaccinated with recombinant OmpH, PlpEC and PlpE formulated with oil based-CpG adjuvant. OmpH, PlpEC and PlpE formulations provided 50%, 60% and 100% protection, respectively. These findings implicated that recombinant PlpE and PlpEC-OmpH fusion proteins when formulated with oil based-CpG adjuvant are potent acellular vaccine formulation candidates against shipping fever.

The objective of this investigation was to evaluate the effects of administering CpG-ODN to commercial strain chickens as a potential adjuvant to vaccination against Salmonella, Eimeria spp., and Newcastle disease virus, or immunization to bovine serum albumin (BSA). During Experiment 1, which evaluated the dual application of CpG-ODN and a Newcastle disease virus vaccine, in the first of three replicate trials, on day 28 of the experiment, animals in the Vaccine + CpG 1& 14 experimental group were observed to have the highest levels of (p<0.05) anti-NDV IgG in serum. These levels were elevated above levels in animals from all other experimental groups. This suggestion for an adjuvant effect associated with CpG-ODN administration was not supported in the remaining two trials of experiment 1. Experiment 2 evaluated the potential for CpG-ODN to adjuvant a commercial live oocyst coccidial vaccine when applied by an oral route to neonatal broiler chickens. Overall, when body weight gain during challenge, development of intestinal lesions, and anti-Eimeria IgG levels were evaluated, vaccine administration alone was demonstrated to provide the best measure of protection among animals in all experimental groups, including those receiving either CpG-ODN or Non CpG-ODN. Experiment 3 investigated the simultaneous administration of CpG-ODN or Non-CpG ODN and a commercially acquired Salmonella typhimurium vaccine to SCWL chickens. Similar to experiments 1 and 2, antigen specific IgG responses in serum and indices of protection against field strain Salmonella challenge were variable and inconsistent. Anti-BSA IgG levels were compared in broiler and SCWL chickens immunized against BSA by a drinking water route of administration alone, or in combination with two different concentrations of CpG-ODN or Non CpG-ODN in experiment 4. The only observation where CpG-ODN and BSA co-administration resulted in anti-BSA IgG levels that were elevated above BSA alone immunized chickens was measured in broilers at day 19 post-final immunization. Taken together, given the variable results reported in this investigation related to the co-administration of ODN and vaccine or protein antigen, these data are largely inconclusive for suggesting that CpG-ODN can effectively adjuvant humoral immune responses in commercial strain chickens.