Vaccination and the use of immune stimulants are two important ways to mitigate the costs of disease in fish aquaculture. A vaccine to Enteric redmouth disease (ERM) was the first licensed fish vaccine in the world. Although effective in protecting fish from the motile bacterial (Yersinia ruckeri) infection, ERM can occur in ERM vaccinated fish due to the rise of non-motile Y. ruckeri that does not express flagellin. This highlighted the need for continual improvement of vaccine efficacy and the importance of flagellin in fish immune responses. In this thesis the immune response to the ERM vaccine was studied first to give insights for vaccine development. A recombinant flagellin from Y. ruckeri (YRF) was then produced and its bioactivities were investigated in vitro and in vivo. The immune response to ERM vaccination was studied in rainbow trout in two major and relevant immune organs, the spleen and gills. Intraperitoneal injection of the ERM vaccine induces an early balanced expression of pro- and anti-inflammatory cytokines and adaptive cytokines in the spleen, with a heightened expression of acute phase proteins (APPs) and anti-microbial peptides (AMPs) in both spleen and gills. The analysis suggests that ERM vaccination activates host innate immunity and the expression of specific IL-12 and IL-23 isoforms leading to a Th1 and Th17 biased immune responses. This study has increased our understanding of the host immune response to ERM vaccination and the adaptive pathways involved. The early responses of a set of genes established in this study may prove useful as biomarkers in future vaccine development in aquaculture. YRF was next produced in a bacterial system, and purified. Its bioactivity was investigated first in the trout macrophage cell line RTS-11 and head kidney primary cell cultures. YRF is a potent activator of pro-inflammatory cytokines, APPs, AMPs and subunits of the IL-12 cytokine family in vitro. This property was further confirm in vivo in multiple tissues after intraperitoneal injection of YRF. These results suggest that flagellins are important pathogen-associated molecular patterns (PAMPs) that can activate an inflammatory response in fish not only in vitro but also in vivo. Furthermore, YRF was shown to be the most potent PAMP in vitro, in terms of activation of an inflammatory response, compared to pure LPS and peptidoglycan. In addition, YRF mixed with complete Freund's adjuvant can induce YRF-specific IgM antibodies in rainbow trout. These antibodies are able to neutralize YRF bioactivity, and react against the middle domain of YRF, as assessed in Western blot analysis. When YRF was fused with a protein antigen, it increased the antigen-specific IgM antibody response. This analysis reveals that YRF is a potent activator of host immune responses and can be used as an immune stimulant and adjuvant to improve vaccine efficacy.

Production of an effective vaccine and long-term treatment against human immunodeficiency virus (HIV) is elusive. In this thesis two different techniques were used in an attempt to insert HIV-neutralising monoclonal antibody (IgG1b12) sequences into a simian retroviral gene therapy agent pseudo-typed with vesicular stomatitis virus glycoprotein. Genes were encoded in either a poxvirus split-vector system or a baculovirus expression system. Both systems aim to produce replication incompetent pseudotyped virus like particles with simian origin. It is believed that the resulting non-infectious artificial lentivirus particles enter neighbouring cells, penetrate the nucleus and insert genetic material (the antibody gene) into the mammalian genome. The poxvirus split-vector system used in this project was a Vaccinia Retroviral Hybrid Vector, where recombinant modified vaccinia Ankara (MVA) is used to deliver the simian immunodeficiency virus (SIV) like particles into mammalian cells. However, the MVA system failed to express proteins of interest due to the instability of genetic insertion into the recombinant MVA genome. As an alternative strategy, two different BacMam systems were used to allow the production of VLPs, where mammalian cells are co-transduced with different recombinant baculoviruses (rBVs). VLPs were expressed either under the control of T7 RNA polymerase system or under the cytomegalovirus immediate early gene promoter. The results from the first BacMam system indicated that the T7 RNA polymerase system was not suitable to express detectable levels of proteins. The results indicated that translation of the produced mRNA by T7 promoter is inefficient, most likely because of the absence of RNA 5’ cap structure. To overcome this hybrid BV–T7 system limitation, a different system was developed. Proteins of interest from the second BacMam system were successfully expressed and detected using western blot analysis. VLPs were generated and visualised under electronic microscope. IgG1b12 was secreted in the supernatant of the transduced mammalian cells. Mammalian cells were successfully transduced with multiple different recombinant BVs simultaneously. The study establishes the feasibility of antibody gene transfer, and demonstrates the use of SIV like particles production to transduce mammalian cells using BacMam technology. The technique may have application for use as an immunotherapy of HIV infection as well providing long-acting prevention of HIV infection for those not yet infected with HIV.

No description available.

To evaluate the impact of maternal HIV-infection on routine childhood immunization coverage, comparison was made on the immunization status of children born to HIV-infected and HIV-uninfected women in rural KwaZulu Natal. The study population was all children enrolled in the routine demographic surveillance system as at 31st December 2005 (n=18,171) in Africa Centre Demographic Surveillance Area. Sampling of subjects was done based on the dates of birth that were between the period 1st Jan 2004 and 31st December 2005 (n=2,020). This was further divided based on maternal HIV status namely; 236 HIV (+), 777 HIV (-) and 1,007 HIV (unknown). The main outcome measure was the percent of complete routine childhood immunizations recommended by the WHO as assessed from the Road-to- Health cards or maternal recall during household interviews. For all vaccines, children born to HIV-infected mothers had lower immunization coverage than children born to HIV-negative mothers (78.21% vs. 86.52%). The children of mothers who were HIV-infected were 31-55% (P-value <0.020) less likely to be immunized compared to children of mothers who were HIVuninfected. We conclude that maternal HIV-infection is associated with childhood under immunisation. VCT health workers should encourage HIV-infected mothers to complete childhood immunization. Improving access to immunization services could benefit vulnerable populations such as children born to HIV-infected mothers.

Background: Children are required by law to receive vaccinations to enter school. States and territories offer exemptions for parents who refuse to vaccinate their children. Types of exemptions vary by state or territory, as does the exemption claiming process. The purpose of this research was to identify the various education-related processes implemented by states and territories which allow parents to exempt children from vaccinations. Methods: A questionnaire was distributed to immunization managers in the 50 United States, District of Columbia, the United States Indian Health Service, and eight United States territories. Managers reported vaccination requirements for their jurisdiction (collectively referred to as "state"). Education-related questions, identified which states required parents to: 1) read and sign a vaccination risk/benefit statement prior to exemption; 2) complete mandatory vaccine education before obtaining vaccination exemption; 2a) complete education within a certain time period before school admission; and 2b) have parental vaccine education regulated. Results: A parent-signed risk/benefit statement was required by 25 states for religious exemptions, 12 states for personal exemptions, 10 states for medical exemptions, and 1 state for temporary medical exemptions. Thirteen states required mandatory parental vaccine education prior to obtaining an exemption. Vaccine education could be completed at various times prior to school admission. For most states, the mandated parental vaccine education prior to exemption was regulated by law, administrative rule, or policy. Conclusions: Implementing a risks/benefits statement prior to granting an exemption may not be helpful in reducing religious and personal exemption rates. The process of providing vaccine education prior to exemption varies greatly between states. Familiarity with various state vaccine education requirements may aid policymakers who are considering enacting mandatory vaccine education in his or her state.

According to the Centers for Disease Control and Prevention (CDC), there are approximately 14 million new cases of HPV diagnosed each year (men and women combined). The rate of vaccine administration among adolescent males is much less than it is among females. As a result, the CDC has urged health care providers to work with state and local health care providers to improve the utilization of the HPV vaccine. The purpose of this scholarly project was to develop an educational toolkit, one guided by Ajzen and Fishbein's theory of reasoned action, regarding the value of the HPV vaccine. The toolkit was offered through both online and hard copy formats and provided parents of adolescent males with information regarding HPV, the HPV vaccine, helpful websites, and references. The toolkit's efficacy will be determined by a comparison of annual vaccination rates. This project fills a significant knowledge gap in the scholarly literature, as there were only 8 articles that met the inclusion criteria in the review of literature. It also provides a guide for other outpatient clinics that may want to implement a comparable toolkit.

Thesis (MPH)--University of Limpopo, 2010. / Introduction: Hepatitis B is a serious liver disease caused by the hepatitis B virus (HBV), with an estimated 360 million chronic infections worldwide, about a million of which die each year from chronic liver diseases. In South Africa (SA) over 50% of the population has been infected by HBV, and at least 3 million people are chronic HBV carriers. Chronic HBV carriers have the potential of transmitting HBV parenterally in the hospital setting, thus health care workers (HCWs) are at risk of contracting HBV, with the most likely exposure being via a needle stick injury (NSI). There is an effective vaccine against HBV which is recommended by the SA Department of Health, yet previous studies have shown that most HCWs are not vaccinated. Aim and objectives: The study aimed to investigate the knowledge, attitudes and practices regarding hepatitis B vaccination amongst HCWs in the Ekurhuleni Metro. Objectives were to determine: (1) the level of knowledge of HCWs about vaccination against HBV; (2) the attitudes of HCWs towards vaccination against HBV; (3) the practices of HCWs regarding HBV prevention and (4) the barriers to / predictors for effective HBV vaccination among HCWs at Ekurhuleni Metro Materials and Methods: This was a cross-sectional descriptive study which made use of a self-administered questionnaire that was sent to Ekurhuleni nurses and doctors who were working in 3 public hospitals, 7 district clinics, and 110 general practices. Results: Two hundred and fifteen questionnaires were distributed and 161 were returned giving an overall response rate of 74.9%. HCWs do not report their NSI; over a third [37.6% (41/81)] always reported the NSI; while 72% (116/161) of HCWs had been vaccinated, only 61.2% (71/116) of those vaccinated had received all 3 doses of the vaccine. For knowledge of HBV vaccination, 66.5% (107/161) scored poor; 31.7% (51/161) scored moderate; and 1.8% (3/161) scored high. For attitudes towards HBV vaccination, 0.6% (1/160) scored negative; 24.4% (39/160) scored neutral; and 74.5% (120/160) scored positive. A positive attitude score was a significant predictor for being vaccinated (OR=1.13, p=0.007) Conclusion: Guidelines should be put in place to increase vaccination uptake and reduce the risk of exposure to HBV infection by HCWs

The recombinant Hepatitis B surface antigen vaccine inadequately protects those living with HIV from Hepatitis B virus infection. This study utilized saved serum samples from a retrospective cohort of persons with HIV and documented vaccine-induced HBsAb seroconversion to determine factors associated with persistence of protective levels of HBsAb (≥10mIU/ml). HBsAb levels fell below 10mIU/ml in 27% of the cohort after a median follow-up of 43 months. HIV viral load suppression (<50copies/ml) at the time of vaccination was the major factor associated with persistence of protective levels of HBsAb (OR 3.83, p <0.01). Among individuals who lost protective levels of HBsAb, booster doses of vaccine re-instated the development of protective levels of HBsAb. Delaying or repeating HBV vaccination until after suppression of HIV viral load is achieved should be considered HBV antibody levels should be followed over time and boosters given with loss of protective levels of HBsAb.

The recombinant Hepatitis B surface antigen vaccine inadequately protects those living with HIV from Hepatitis B virus infection. This study utilized saved serum samples from a retrospective cohort of persons with HIV and documented vaccine-induced HBsAb seroconversion to determine factors associated with persistence of protective levels of HBsAb (≥10mIU/ml). HBsAb levels fell below 10mIU/ml in 27% of the cohort after a median follow-up of 43 months. HIV viral load suppression (<50copies/ml) at the time of vaccination was the major factor associated with persistence of protective levels of HBsAb (OR 3.83, p <0.01). Among individuals who lost protective levels of HBsAb, booster doses of vaccine re-instated the development of protective levels of HBsAb. Delaying or repeating HBV vaccination until after suppression of HIV viral load is achieved should be considered HBV antibody levels should be followed over time and boosters given with loss of protective levels of HBsAb.

Human Papilloma virus (HPV) can lead to cervical cancer, a common form of cancer in Sweden and globally. A vaccine has been developed for the most carcinogenic strains of HPV. In Sweden it is planned that the vaccine be included in the public national vaccination program for children. The aim of this study was to illustrate attitudes towards future sexual habits and preventive cervical cancer screening among young women and parents of girls vaccinated against HPV. This study is a part of a larger project where interviews with young women aged 17 to 26 years and parents of girls aged 13 to 17 years compose the foundation. In this study the interviews were analysed with qualitative latent content analysis, all together 21 interviews. The main result was that in both groups it was generally thought that neither future sexual habits nor participation in cervical cancer screening would be considerably affected. The young women however had deficient knowledge about what they were vaccinated against and the purpose of cervical cancer screening. The parents had better understanding. Accurate information about HPV, the HPV vaccine and cervical cancer screening in connection with vaccination is important for the outcome of future sexual habits and participation in cervical cancer screening. / Humant papillomvirus (HPV) kan leda till cervixcancer som är en vanlig cancersort både i Sverige och globalt. Ett vaccin har utvecklats mot de mest onkogena HPV-typerna. I Sverige ska HPV-vaccinet ingå i det allmänna nationella vaccinationsprogrammet för barn. Syftet med studien var att belysa inställningen till framtida sexualvanor och gynekologiska cellprovskontroller (GCK) bland unga kvinnor och föräldrar till flickor som HPV-vaccinerats. Denna studie är en del av ett större projekt där intervjuer med unga kvinnor 17-26 år samt med föräldrar till flickor 13-17 år utgör grunden. I denna studie analyserades intervjuerna med kvalitativ latent innehållsanalys, sammanlagt 21 intervjuer. Det huvudsakliga resultatet som framkom var att majoriteten av de unga kvinnorna och föräldrarna till flickorna inte trodde att framtida sexualvanor skulle förändras samt att deltagande i framtida GCK inte skulle påverkas nämnvärt. Det framkom dock att de unga kvinnorna hade bristfälliga kunskaper om vad de var vaccinerade emot och vad GCK var. Föräldrarna till flickorna hade större kunskap om vad vaccinering och GCK innebar än de unga kvinnorna. Vikten av rätt sorts information om HPV, HPV-vaccin och GCK i samband med vaccination framkom som ett betydande resultat för utfallet för de framtida sexualvanorna och deltagandet i GCK.