Acceptability and Feasibility of Reiki for Symptom Management in Children Receiving Palliative Care

Complementary therapies are chosen by parents of children receiving palliative care to augment the use of traditional medications for symptom management without the increased side effects additional medications may bring. Pain and anxiety are common symptoms for children receiving palliative care. Reiki therapy is a light touch therapy that has been examined in adults but not with children until recently. This dissertation addresses the evidence for complementary therapies for children experiencing pain and anxiety, Reiki therapy for pain and anxiety in adults, and evidence based complementary therapies for young children considering developmental stage. The main study is a quasi-experimental mixed methods pilot study design examining the acceptability and the feasibility of a Reiki therapy intervention for children ages 7 to 16 years receiving palliative care. We measured pain, anxiety, and relaxation operationalized as heart and respiratory rates pre and post Reiki therapy interventions at each of two home visits. We completed a structured interview separately with parents and children to elicit their views on the Reiki therapy experience. Paired student t-tests or Wilcoxon signed rank tests were calculated comparing the pre and post Reiki scores separately for verbal and non-verbal children for each treatment, over the entire intervention, and independent sample t-tests or Mann-Whitney tests comparing children based on demographic variables. We approached 24 child-parent dyads, 21 (87.5%) agreed to participate and signed consents while 3 (12.5%) declined to participate. Of the 21 dyads, 16 completed the study (eight verbal and eight non-verbal children). Statistical significance was obtained for verbal children for heart rate for treatment two (t=3.550, p = 0.009) and for nonverbal children for pain for treatment two (Z = -2.023, p = 0.063); however effect sizes using Cohen’s d levels were medium to large for both verbal and non-verbal children for pain and anxiety. Children and their parents told us their experiences with Reiki therapy. Themes found in interviews augment the quantitative results. Themes included Feeling Better, Hard to Judge, and Still Going On, which helped clarify the quantitative results. Results support further study of Reiki therapy for symptom management in children

The Ohio State University Dream Team: Innovation for Well-being fellowship and coaching program

Abstract Background: Nearly 70% of faculty experience very high levels of stress. Integrative Nurse Coaching (INC) can help by assisting clients in establishing goals and embarking on new lifestyle behaviors that help to decrease perceived stress, achieve work life integration, and enhance life satisfaction. Our goal was to evaluate a faculty coaching and fellowship program to support faculty well-being while developing innovation competency. Methods: We employed an INC paradigm to coach five faculty to build confidence and competence in innovation and enhance well-being. We offered monthly group and individual coaching and used a qualitative research thematic analysis to determine themes important for the fellow and group experiences, identify outcomes, and create recommendations for the future. Results: We identified the following themes as outcomes for our program: (1) enhanced connection, comradery, and support; (2) increased confidence and competence in navigating academia; (3) shift from a fixed mindset to an innovation mindset; and (4) increased ability to identify and manage stress and burnout. Fellows also experienced a shift from focusing on individual needs to addressing the needs of the community at the college. Conclusion: Nurse coaching is an effective strategy to address faculty stress and burnout. Additional research is needed to evaluate the Innovation for Well-being faculty fellowship program and its impact on the academic community

A proof-of-concept study for the design of a VLP-based combinatorial HPV and placental malaria vaccine

Abstract In Africa, cervical cancer and placental malaria (PM) are a major public health concern. There is currently no available PM vaccine and the marketed Human Papillomavirus (HPV) vaccines are prohibitively expensive. The idea of a combinatorial HPV and PM vaccine is attractive because the target population for vaccination against both diseases, adolescent girls, would be overlapping in Sub-Saharan Africa. Here we demonstrate proof-of-concept for a combinatorial vaccine utilizing the AP205 capsid-based virus-like particle (VLP) designed to simultaneously display two clinically relevant antigens (the HPV RG1 epitope and the VAR2CSA PM antigen). Three distinct combinatorial VLPs were produced displaying one, two or five concatenated RG1 epitopes without obstructing the VLP’s capacity to form. Co-display of VAR2CSA was achieved through a split-protein Tag/Catcher interaction without hampering the vaccine stability. Vaccination with the combinatorial vaccine(s) was able to reduce HPV infection in vivo and induce anti-VAR2CSA IgG antibodies, which inhibited binding between native VAR2CSA expressed on infected red blood cells and chondroitin sulfate A in an in vitro binding-inhibition assay. These results show that the Tag/Catcher AP205 VLP system can be exploited to make a combinatorial vaccine capable of eliciting antibodies with dual specificity

A VAR2CSA:CSP conjugate capable of inducing dual specificity antibody responses

Background: Vaccine antigens targeting specific P. falciparum parasite stages are under pre-clinical and clinical development. It seems plausible that vaccine with multiple specificities will offer higher protection. With this hypothesis, we exploited the Spy- Tag/SpyCatcher conjugation system to make a, post expression, dual antigen conjugate vaccine, comprising two clinically tested antigen candidates (CSP and VAR2CSA).Methods: The DBL1x-DBL2x-ID2a region of VAR2CSA was genetically fused with SpyTag at N-terminus. The full-length CSP antigen was genetically fused to C-terminal SpyCatcher peptide. The covalent interaction between SpyTag/ SpyCatcher enables the formation of DBL1x-DBL2x-ID2a:CSP conjugate vaccine. Immunogenicity and quality of antibody responses induced by the conjugate vaccine, as well as a control CSP-SpyCatcher vaccine, was tested in BALB/c mice.Results: Serum samples obtained from mice immunized with the conjugate vaccine were able to recognize both untagged DBL1x-DBL2x-ID2a as well as CSP antigen. Moreover, the geometric mean anti-CSP antibody titer was 1.9-fold higher in serum (at day 35 and 55 post-first immunization) from mice immunized with the conjugate vaccine, as compared to mice receiving the control vaccine.Conclusion: The data obtained in this study serves as proof-of-concept for the simultaneous induction of antibodies directed against individual antigen components in a dual stage anti-malaria vaccine.Keywords: Malaria vaccine, Circumsporozoite protein, VAR2CSA, CSP SpyCatcher, SpyTag-DBL1x-DBL2x-ID2a, bacterial superglue, DBL1x-DBL2x-ID2a:CSP conjugat

A vaccine displaying a trimeric influenza-A HA stem protein on capsid-like particles elicits potent and long-lasting protection in mice

Due to constant antigenic drift and shift, current influenza-A vaccines need to be redesigned and administered annually. A universal flu vaccine (UFV) that provides long-lasting protection against both seasonal and emerging pandemic influenza strains is thus urgently needed. The hemagglutinin (HA) stem antigen is a promising target for such a vaccine as it contains neutralizing epitopes, known to induce cross-protective IgG responses against a wide variety of influenza subtypes. In this study, we describe the development of a UFV candidate consisting of a HAstem trimer displayed on the surface of rigid capsid-like particles (CLP). Compared to soluble unconjugated HAstem trimer, the CLP-HAstem particles induced a more potent, long-lasting immune response and were able to protect mice against both homologous and heterologous H1N1 influenza challenge, even after a single dose

HER2 cancer vaccine optimization by combining Drosophila S2 insect cell manufacturing with a novel VLP-display technology

Breast cancer is a widespread oncology indication affecting more than 1.3 million people worldwide annually, 20%-30% of which are HER2 positive. HER2 is a tyrosine kinase receptor that is frequently overexpressed in several solid-tumor cancers (incl. breast, prostate, gastric, esophageal and osteosarcoma) where it denotes an aggressive phenotype, high metastatic rate, and poor prognosis. In a human context, passive HER2-targeted immunotherapy using monoclonal antibodies (mAb, e.g. Trastuzumab and Pertuzumab) has proven to be an effective treatment modality, which has dramatically improved clinical outcomes. Unfortunately, mAb therapy is very expensive and the repeated injections of high doses can be associated with severe side-effects that reduce efficacy. Vaccines are highly cost-effective, but overall progress in development of anti-cancer vaccines based on cancer-associated antigens (e.g. HER2) has been hampered by inherent immune-tolerogenic mechanisms rendering the immune system incapable of reacting against the body’s own cells/proteins (i.e. self-antigens). Consequently, many attempts to develop anti-cancer vaccines have failed in clinical trials due to insufficient immunogenicity. To circumvent this central issue, we have developed a proprietary virus-like particle (VLP)-based vaccine delivery platform. Notably, the VLP-platform is currently the only available technology to effectively facilitate multivalent “virus-like” display of large/complex vaccine antigens. This is key to overcome immune-tolerance and enable induction of therapeutically potent antibody responses directed against cancer-associated self-antigens. In this talk I will discuss the non-viral Drosophila S2 insect cell production system and how it was applied to the production of hHer2/neu antigen, including using advanced production methods such as perfusion for clinical material manufacture. Furthermore, I will present our data from a transgenic mouse model for spontaneous breast cancer development, where high-density display of the HER2 extracellular domain on the surface of virus-like particles (VLPs) enables induction of therapeutically potent anti-HER2 responses. Split-protein tag/catcher conjugation was used to facilitate directional covalent attachment of HER2 to the surface of icosahedral bacteriophage-derived VLPs, thereby harnessing the VLP platform to effectively overcome B-cell tolerance. Vaccine efficacy was demonstrated both in prevention and therapy of mammary carcinomas in HER2 transgenic mice. Thus, the HER2-VLP vaccine shows promise as a new strategy for treatment of HER2-positive cancer. The modular VLP system may also represent an effective tool for development of self-antigen based vaccines against other non-communicable diseases

A VAR2CSA:CSP conjugate capable of inducing dual specificity antibody responses.

Background: Vaccine antigens targeting specific P. falciparum parasite stages are under pre-clinical and clinical development. It seems plausible that vaccine with multiple specificities will offer higher protection. With this hypothesis, we exploited the SpyTag/SpyCatcher conjugation system to make a, post expression, dual antigen conjugate vaccine, comprising two clinically tested antigen candidates (CSP and VAR2CSA). Methods: The DBL1x-DBL2x-ID2a region of VAR2CSA was genetically fused with SpyTag at N-terminus. The full-length CSP antigen was genetically fused to C-terminal SpyCatcher peptide. The covalent interaction between SpyTag/SpyCatcher enables the formation of DBL1x-DBL2x-ID2a:CSP conjugate vaccine. Immunogenicity and quality of antibody responses induced by the conjugate vaccine, as well as a control CSP-SpyCatcher vaccine, was tested in BALB/c mice. Results: Serum samples obtained from mice immunized with the conjugate vaccine were able to recognize both untagged DBL1x-DBL2x-ID2a as well as CSP antigen. Moreover, the geometric mean anti-CSP antibody titer was 1.9-fold higher in serum (at day 35 and 55 post-first immunization) from mice immunized with the conjugate vaccine, as compared to mice receiving the control vaccine. Conclusion: The data obtained in this study serves as proof-of-concept for the simultaneous induction of antibodies directed against individual antigen components in a dual stage anti-malaria vaccine