Prime Strategy Research Articles

Bi-PE: bi-directional priming improves CRISPR/Cas9 prime editing in mammalian cells.

Prime editors consisting of Cas9-nickase and reverse transcriptase enable targeted precise editing of small DNA pieces, including all 12 kinds of base substitutions, insertions and deletions, while without requiring double-strand breaks or donor templates. Current optimized prime editing strategy (PE3) uses two guide RNAs to guide the performance of prime editor. One guide RNA carrying both spacer and templating sequences (pegRNA) guides prime editor to produce ssDNA break and subsequent extension, and the other one produces a nick in the complementary strand. Here, we demonstrated that positioning the nick sgRNA nearby the templating sequences of the pegRNA facilitated targeted large fragment deletion and that engineering both guide RNAs to be pegRNAs to achieve bi-direction prime editing (Bi-PE) further increase the efficiency by up to 16 times and improved the accuracy of editing products by 60 times. In addition, we showed that Bi-PE strategy also increased the efficiency of simultaneous conversion of multiple bases but not single base conversion over PE3. In conclusion, Bi-PE strategy expanded the editing scope and improved the efficiency and the accuracy of prime editing system, which might have a wide range of potential applications.

Evaluation of prime and prime-boost immunization strategies in BALB/c mice inoculated with Leishmania infantum transfected with toxic plasmids

The etiologic agents of visceral leishmaniasis are Leishmania infantum and Leishmania donovani. Despite the variety of drugs available to treat leishmaniasis, most lead to serious adverse effects, and resistance to these drugs has been reported. Currently, no leishmaniasis vaccine is available for humans. That is why the group developed transgenic L. infantum promastigote lines, which express toxic proteins after differentiation into amastigotes. That is why group developed the pFL-AMA plasmid and transfected it into L. Infantum promastigotes. This plasmid was expressed only in the amastigote form of the parasite. Sequences encoding toxic proteins (active bovine trypsin and egg avidin) were inserted in this plasmid, and the transfected parasites died after the differentiation process. In this study, two immunization protocols were performed in BALB/c mice: prime and prime-boost immunization prior to challenge with the wild-type L. infantum (WT). The parasite burdens in the spleen, liver, and bone marrow were evaluated to verify immunological protection. Histopathological analysis of the spleen and liver and the humoral immune response were also performed. The data showed that the parasite burden was reduced in prime-boosted mice in the spleen, liver, and bone marrow, indicating that mice immunized with two doses of the transfected parasites were satisfactorily protected. High levels of IgG, IgG1, and IgG2a antibodies were observed, as well as the presence of anti-inflammatory cytokine Interleukine-10 and pro-inflammatory cytokine Tumor Necrosis Factor-α (TNF-α) and Interferon-γ (IFN – γ) suggesting a Th1/Th2 mix response, in addition to the presence of multinucleated giant cells in the spleen and lymphocyte infiltration in the liver. Therefore, L. infantum transfected with a toxic plasmid is an excellent vaccine candidate against visceral leishmaniasis and the application of a boost before the challenge promotes greater protection against WT L. infantum infection.

Effects of crystalloid and colloid priming strategies for cardiopulmonary bypass on colloid oncotic pressure and haemostasis: a meta-analysis.

OBJECTIVESColloid oncotic pressure (COP) is an important factor in cardiac surgery, owing to its role in haemodilution. The effect of cardiopulmonary bypass prime fluids on the COP is unknown. In this study, the effect of crystalloid and colloid prime fluids, with or without retrograde autologous priming (RAP), on the COP during elective cardiac surgery was evaluated.METHODSRandomized controlled trials and prospective clinical trials comparing crystalloid and colloid priming fluids or with RAP were selected. The primary outcome was the COP; secondary outcomes were fluid balance, fluid requirements, weight gain, blood loss, platelet count and transfusion requirements.RESULTSFrom 1582 records, 29 eligible studies were identified. COPs were comparable between gelofusine and hydroxyethyl starch (HES) during bypass [mean difference (MD): 0.69; 95% confidence interval (CI): −2.05, 3.43; P = 0.621], after bypass (MD: −0.11; 95% CI: −2.54, 2.32; P = 0.930) and postoperative (MD: −0.61; 95% CI: −1.60, 0.38; P = 0.228). Fluid balance was lower with HES than with crystalloids. RAP reduced transfusion requirements compared with crystalloids. Blood loss was comparable between groups.CONCLUSIONSCOPs did not differ between crystalloids and colloids. As a result of increased transcapillary fluid movement, fluid balance was lower with HES than with crystalloids. Haematocrit and transfusion requirements were comparable between groups. However, the latter was lower when RAP was applied to crystalloid priming compared with crystalloids alone. Finally, no differences in blood loss were observed between the groups.

Immune characterization in platinum resistant ovarian cancer patients treated with pembrolizumab and guadecitabine

Abstract Immune checkpoint inhibitors (ICI) have limited activity in ovarian cancer (OC). Accumulating preclinical and early clinical results support that interventions targeting the epigenome could elicit an inflamed tumor milieu to augment ICI. Here we explore the clinical and biological activity of guadecitabine, a second generation Hypomethylating agents (HMA), given in low dose as a priming strategy before pembrolizumab, a humanized anti-PD1 antibody in a clinical trial for patients with recurrent, platinum-resistant OC. Among 35 evaluable patients, there were 3 partial responses (8.6%) and 8 (22.9%) patients with stable disease, resulting in clinical benefit rate (CBR) of 31.4%. Median duration of clinical benefit was 6.8 months. High dimensional immune profiling of PBMCs showed higher frequency of naive and/or central memory CD4+ T cells and of classical monocytes in patients with durable CBR. Higher baseline density of CD8+ T and CD20+ B cells and presence of tertiary lymphoid structures in tumors were associated with durable CBR. The molecular features such as expression levels of PD-L1 or A2AR linked to therapeutic benefit for resistant OC. Our study provides an in-depth view of the immune milieu of platinum resistant OC and of the effects of the combination of HMAs and pembrolizumab on the interactions between immune cell populations and tumor cells. Supported by USAMRMC/CDMRP (W81XWH170141)

Toward Improved Bioremediation Strategies: Response of BAM-Degradation Activity to Concentration and Flow Changes in an Inoculated Bench-Scale Sediment Tank.

Compound-specific isotope analysis (CSIA) can reveal mass-transfer limitations during biodegradation of organic pollutants by enabling the detection of masked isotope fractionation. Here, we applied CSIA to monitor the adaptive response of bacterial degradation in inoculated sediment to low contaminant concentrations over time. We characterized Aminobacter sp. MSH1 activity in a flow-through sediment tank in response to a transient supply of elevated 2,6-dichlorobenzamide (BAM) concentrations as a priming strategy and took advantage of an inadvertent intermittence to investigate the effect of short-term flow fluctuations. Priming and flow fluctuations yielded improved biodegradation performance and increased biodegradation capacity, as evaluated from bacterial activity and residual concentration time series. However, changes in isotope ratios in space and over time evidenced that mass transfer became increasingly limiting for degradation of BAM at low concentrations under such stimulated conditions, and that activity decreased further due to bacterial adaptation at low BAM (μg/L) levels. Isotope ratios, in conjunction with residual substrate concentrations, therefore helped identifying underlying limitations of biodegradation in such a stimulated system, offering important insight for future optimization of remediation schemes.

An Analysis of Higher Education Policy Act 101 of 1997

The South African higher education sector is one of the most contested sectors with high policy influxes since the beginning of current democratic dispensation. From a horrendous past where it endured the repressive strategy that disenfranchised majority of the population, the country’s higher education system undoubtedly needed a thorough reshape to meet the then changing national development needs and aspirations of the newly elected democratic government. Hence, the prime strategy of redressing past imbalances and inequalities accruing from pre-democratic era, was justified through Higher Education Policy (HEP) Act 101 – whose operational consistency is evident in the past twenty-five years. This synoptic review focuses on HEP Act 101 by unravelling the circumstances presaging its formation, the policy provisions and amendments – whose sectional highlights are also embodied herein. The brief prelude to the policy’s penultimate silver-jubilee forms an agendum for extensive research on its performance over the last quarter-century, while the ensuing discourse aims to channel scholarly attention on critical matters that may inform a new HEP formation or amendment, that will be more agreeable with contemporary socioeconomic needs of the masses and synchronous to new national development goals in the long run.

한국의 Artemis 국제공동 유인달탐사 참여를 중심으로 우리나라 심우주탐사 로드맵 제안

Korea is near close the success on the indigenous launch vehicle KSLV-2 after the second test launch during the second half of 2022, and the satellite development has been already in the level of advanced country. After the such mature of satellite and launch vehicle technologies, Korea’s space development main theme should be ‘Space Exploration and Space Application’, and paradigm should be changed from ‘Hardware’ to ‘Scientific/Technological Mission’, from ‘Unmanned’ to ‘Manned’. Korea’s prime space strategy should be the direction of expansion of space industry, creation of employment and secure the key technologies, improvement of convenience and safety of people. For the purpose it is necessary to start ‘Manned Space Development’ such that participation to ‘Artemis and Gateway Program’ in 20s’ and manned Mars exploration in 30s’ which would be carried out by means of global international cooperation, and which could be a good opportunity to explore the new area of space development and upgrade national technology capability. Taking advantage of this opportunity, it is required for Korea to join the international programs through developing indigenous challenging, sustainable Korean mission and hardware. Also selection of the 2nd Korean Astronaut could draw national attention, especially could give dreams to young generation. Participation to the Artemis program could be the opportunity of entering the major space fairing nation and boosting up national pride. In this study we survey and analyze the Artemis Program in detail, and in conclusion we suggest the strategy of Korea’s participation to the Artemis Program.

Changes in the Transcriptome Profiles of Human Amnion-Derived Mesenchymal Stromal/Stem Cells Induced by Three-Dimensional Culture: A Potential Priming Strategy to Improve Their Properties.

Mesenchymal stromal/stem cells (MSCs) are believed to function in vivo as a homeostatic tool that shows therapeutic properties for tissue repair/regeneration. Conventionally, these cells are expanded in two-dimensional (2D) cultures, and, in that case, MSCs undergo genotypic/phenotypic changes resulting in a loss of their therapeutic capabilities. Moreover, several clinical trials using MSCs have shown controversial results with moderate/insufficient therapeutic responses. Different priming methods were tested to improve MSC effects, and three-dimensional (3D) culturing techniques were also examined. MSC spheroids display increased therapeutic properties, and, in this context, it is crucial to understand molecular changes underlying spheroid generation. To address these limitations, we performed RNA-seq on human amnion-derived MSCs (hAMSCs) cultured in both 2D and 3D conditions and examined the transcriptome changes associated with hAMSC spheroid formation. We found a large number of 3D culture-sensitive genes and identified selected genes related to 3D hAMSC therapeutic effects. In particular, we observed that these genes can regulate proliferation/differentiation, as well as immunomodulatory and angiogenic processes. We validated RNA-seq results by qRT-PCR and methylome analysis and investigation of secreted factors. Overall, our results showed that hAMSC spheroid culture represents a promising approach to cell-based therapy that could significantly impact hAMSC application in the field of regenerative medicine.

A Survey Into the Use of Priming Techniques Implemented by Athletes and Coaches to Improve Athletic Performance.

Collins, J, Bishop, C, Hills, F, Spiegelhalter, A, Cohen, R, and Turner, A. A survey into the use of priming techniques implemented by athletes and coaches to improve athletic performance. J Strength Cond Res 37(1): 107-113, 2023-This study aimed to examine the frequency and modes of psychological priming techniques and strategies being implemented by athletes of a variety of performance levels. A 15-question, anonymous questionnaire was developed and shared via social media sites. The survey implemented a quantitative method approach to collect background information (e.g., demographics, competition, and training history), the prevalence of priming, and the methods used. Ninety subjects met the inclusion criteria (71 men, 18 women, and 1 subject did not identify their sex), with a median age of 28 ± 7.47 years (range, 24-33 years) and training experience of 11 ± 7.57 years (range, 8-18 years). Self-selected participation level accounted for 11 professional, 17 semiprofessional, and 54 amateur-level athletes. Priming strategies were implemented by 79% of subjects without the use of a coach, 10% used strategies with their coach, and 11% did not prime. For athletes, music was the preferred choice (27%), followed by instructional self-talk (24%), motivational self-talk (23%), applied physical actions (20%), and watching videos clips (6.3%). Coaches preferred motivational statements with 55% implementing this technique, followed by 27% using inspiring team talks, and only 18% playing music. Of those who implemented a priming strategy, 66% found them to be either "very" or "extremely" effective," With 38% of subjects feeling that priming accomplished this through increased motivation, 22% felt that it reduced their fear and anxiety, 21% thought that it improved their intensity, 15% felt that it increased strength and power, and 2% felt that it improved endurance. The chi-square test also found a significant (φc = 0.27; p = 0.011) relationship with the use of priming to increase motivation. These results demonstrate that priming strategies are being used irrespective of coach intervention; therefore, educating coaches and athletes on the implementation of priming techniques has its place when aiming to improve athlete performance.

Cell Membrane-Camouflaged Liposomes and Neo-Peptide-Loaded Liposomes with Tlr Agonist R848 Provides a Prime and Boost Strategy for Efficient Personalized Cancer Vaccine Therapy

Cell Membrane-Camouflaged Liposomes and Neo-Peptide-Loaded Liposomes with Tlr Agonist R848 Provides a Prime and Boost Strategy for Efficient Personalized Cancer Vaccine Therapy

Analysis of Livelihoods and Food Security among Rural Households of Khyber Pakhtunkhwa, Pakistan

Purpose: This study was an effort with the aim to study livelihoods and food security status in rural areas of Khyber Pakhtunkhwa province, Pakistan.
 Design/Methodology/Approach: Three districts of the province were confined and research data from randomly selected 336 households were collected. Livelihoods was analyzed by investigating livelihood strategies pursued by the households while food security status was measured through calorie intake method.
 Findings: The study examined that diversified livelihood strategies were pursued by the households; and noticed that farm was the prime strategy of 34.52% households while non-farm was the strategy of 65.48% households The incidence of food secure and insecure households was 57.44% and 42.56%, respectively; and FSI of the food secure households averaged 1.26 and food insecure households averaged 0.79.
 Implications/Originality/Value: There is dire need to provide opportunities for a sustainable livelihood strategy at household level that could ultimately move them from worse to better food security status.

Priming strategies for controlling stem cell fate: Applications and challenges in dental tissue regeneration

Priming strategies for controlling stem cell fate: Applications and challenges in dental tissue regeneration

Priming strategies for controlling stem cell fate: Applications and challenges in dental tissue regeneration.

Mesenchymal stromal cells (MSCs) have attracted intense interest in the field of dental tissue regeneration. Dental tissue is a popular source of MSCs because MSCs can be obtained with minimally invasive procedures. MSCs possess distinct inherent properties of self-renewal, immunomodulation, proangiogenic potential, and multilineage potency, as well as being readily available and easy to culture. However, major issues, including poor engraftment and low survival rates in vivo, remain to be resolved before large-scale application is feasible in clinical treatments. Thus, some recent investigations have sought ways to optimize MSC functions in vitro and in vivo. Currently, priming culture conditions, pretreatment with mechanical and physical stimuli, preconditioning with cytokines and growth factors, and genetic modification of MSCs are considered to be the main strategies; all of which could contribute to improving MSC efficacy in dental regenerative medicine. Research in this field has made tremendous progress and continues to gather interest and stimulate innovation. In this review, we summarize the priming approaches for enhancing the intrinsic biological properties of MSCs such as migration, antiapoptotic effect, proangiogenic potential, and regenerative properties. Challenges in current approaches associated with MSC modification and possible future solutions are also indicated. We aim to outline the present understanding of priming approaches to improve the therapeutic effects of MSCs on dental tissue regeneration.

IFN-Gamma and TNF-Alpha as a Priming Strategy to Enhance the Immunomodulatory Capacity of Secretomes from Menstrual Blood-Derived Stromal Cells.

Mesenchymal stromal cells isolated from menstrual blood (MenSCs) exhibit a potent pro-angiogenic and immunomodulatory capacity. Their therapeutic effect is mediated by paracrine mediators released by their secretomes. In this work, we aimed to evaluate the effect of a specific priming condition on the phenotype and secretome content of MenSCs. Our results revealed that the optimal condition for priming MenSCs was the combination of interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) that produced a synergistic and additive effect on IDO1 release and immune-related molecule expression. The analyses of MenSC-derived secretomes after IFNγ and TNFα priming also revealed an increase in EV release and in the differentially expressed miRNAs involved in the immune response and inflammation. Proliferation assays on lymphocyte subsets demonstrated a decrease in CD4+ T cells and CD8+ T cells co-cultured with secretomes, especially in the lymphocytes co-cultured with secretomes from primed cells. Additionally, the expression of immune checkpoints (PD-1 and CTLA-4) was increased in the CD4+ T cells co-cultured with MenSC-derived secretomes. These findings demonstrate that the combination of IFNγ and TNFα represents an excellent priming strategy to enhance the immunomodulatory capacity of MenSCs. Moreover, the secretome derived from primed MenSCs may be postulated as a therapeutic option for the regulation of adverse inflammatory reactions.

The Clinical Oncolytic Reovirus Formulation Reolysin Synergistically Augments the Anti-Leukemic Activity of Azacitidine

Despite the recent development of new agents for acute myeloid leukemia (AML) therapy, novel approaches are still needed for patients that do not benefit sufficiently from existing regimens. Reolysin (Pelareorep) is a proprietary clinical formulation of the naturally occurring oncolytic reovirus that is non-pathogenic and preferentially replicates in cancer cells, but not in normal tissue. Although Reolysin has been investigated in over 30 adult clinical trials and is very well tolerated when given alone and in combination with chemotherapy, it has never been evaluated for AML therapy. Our major goal was to determine the efficacy and mechanism of action of Reolysin alone and in combination with azacitidine in AML models and primary patient specimens. Reolysin exhibited dose-dependent effects against AML cells with respect to the reduction in leukemia cell viability and induction of apoptosis in all 8 cell lines evaluated. The combination of Reolysin with azacitidine yielded synergistic benefit across all cell lines that was dramatically superior to single agent treatments (p<0.001). The benefit of combination treatment was confirmed in primary AML specimens (N=14 to date). RNASeq-based transcriptome and gene ontology (GO) analyses of the pharmacodynamic effects of each agent and the combination revealed that the Reolysin and azacitidine combination potently altered multiple genes in the immune response pathway (p<0.001). qRT-PCR analyses and ELISA assays confirmed the broad immunomodulatory effects of the Reolysin plus azacitidine combination. Immune priming strategies that can turn “immune cold” cancers to “immune hot” may significantly augment the benefit of many therapeutic approaches. Basic leucine zipper transcription factor ATF-like 2 (BATF2) is a key tumor suppressor that is absent in AML and certain other malignancies. Its deficiency promotes immune escape of cancer cells. BATF2 exhibits anticancer activity through upregulation of interleukin-12 and the activation of CD8+ T cells and therefore represents a novel new target in anticancer treatment with immune checkpoint inhibitors. Our transcriptome analyses identified BATF2 as one of the most significantly upregulated genes in AML cells following treatment with the Reolysin plus azacitidine combination (p<0.0001). Additional mechanistic studies confirmed that BATF2 induction was a key driver of the anti-leukemic effects of combination treatment. Finally, Reolysin (5 x 10 8 TCID50 IV 1x per week), azacitidine (5 mg/kg SC 2x per week), and the combination were administered to mice bearing MOLM-13 FLT3-ITD+ xenografts for 19 days to assess the efficacy and tolerability of each treatment. Combination treatment was well tolerated and antagonized disease progression significantly more effectively than either monotherapy (p<0.01). Additional in vivo studies more rigorously assessing the immunomodulatory effects of Reolysin and azacitidine in immune competent mice are underway. Our collective data demonstrate that Reolysin is a safe and well tolerated agent with potent immunomodulatory effects that synergistically augments the anti-AML effects of azacitidine. A phase I investigator-initiated clinical trial further investigating the safety and preliminary efficacy of this combination in patients with AML is currently being planned. DisclosuresNo relevant conflicts of interest to declare.

English

Increased salinity stress in environment challenges the seed germination, emergence, and crop yield. The issue carefully demands the seed priming strategies to mitigate the drastic effects of salinity. Current study was conducted to appraise the modulation in germination, photosynthetic pigments, yield, and gas exchange attributes of sesame cultivars (TS-5 and TH-6) to pre-sowing seed treatment with glycinebetaine (GB) under salt stress. Seeds were treated with GB (25 mM) and water prior to sowing for 16 h. Ten seeds of each cultivar were laid down on moistened filter paper (0 mM and 70 mM NaCl) in petri plates to assess the germination attributes under salt stress. In a separate pot experiment, GB primed and water primed seeds were sown in 10 kg sand filled plastic pots. After two weeks of seed sowing, two concentrations of salinity (0 mM and 70 mM) were maintained by dissolving NaCl in full strength Hoagland nutrient solution. Data for germination, gas exchange and yield parameters were collected after one week, two week and ten weeks respectively. Salt stress decreased the germination percentage, plumule/radicle length, number of seeds/plant, Chl a, net photosynthetic rate (PN), stomatal conductance (gs) and transpiration rate (E), while intercellular CO2 concentration (Ci) and ratio of internal to atmospheric CO2 concentration Ci/Ca ratio were increased. However, seed mass/plant, Chl b and carotenoids remained unaffected under salinity. GB mitigated the saline effects by increasing the germination percentage, plumule length, number of seeds/plant and PN and showed nonsignificant effect on radicle length, seed mass per plant and Chl a, b and carotenoid contents. Sesame cultivar TH-6 showed better performance as compared to TS-5 under saline conditions. GB is powerful osmoregulator to minimize salt effect in sesame by enhancing physiological and yield attributes

RESPLENDENT LEADERSHIP OF ALEXANDER THE GREAT: REMINISCENCES AND REFLECTIONS

Leadership is an assiduously cultivated art, and enduring leadership styles are seen as an invaluable asset that is designed to pass from one generation to the next. Since ancient times, the theory of leadership has historically evolved from a narrow, unidimensional concept into the multidimensional status it enjoys today as a prime developmental strategy. Change is the one constant and as situations and people change with the passage of time, workplace skills too need to evolve to keep pace with the prevailing trends. Prime among these are leadership skills that of a necessity need to evolve in order to stay abreast of the competition. Transformational leadership is the need of the hour in every workplace, collective evolution is of paramount importance as work environments and the workforce undergo rapid changes. Leadership skills must be capable of tackling such exponential organisational changes with a constant re-think of possibilities in the path to success. In the recent past, leadership skills and styles have become a topic of intense research with many pivotal studies conducted by the research community which continues to expend efforts to gain a better understanding of this management phenomenon. History abounds with inspiring tales of great leaders, foremost among them being the powerful Greek Emperor,Alexander the Great. History can be an excellent teacher and the success of historical figures such as Alexander from the ancient world can easily be replicated in the modern age. Many crucial leadership lessons can be learnt from the past and they continue to hold good in the technology driven world of today. A valiant emperor and mighty conqueror, King Alexander was an unparalleled military leader who maximised the potential of his soldiers by sharing his vision with his army who led him from one victory to another. A perfect example of a strong, rock solid leadership that was not averse to taking calculated risks in the ancient past to rise to stupendous power, it continues to be relevant in challenging contemporary times for exploring successful modern leadership styles.. This research paper sheds light on the vision and leadership skills of Alexander the Great, a fearless, revolutionary leader and a master tactician, through a meticulous study of his illustrious life and triumphant victories. This qualitative research is based on established historical sources which makes the narrative of one of the most notable emperors in history not only a source of instruction but also an engaging and informative read.

T helper type 1 biased immune responses by PPE17 loaded core-shell alginate-chitosan nanoparticles after subcutaneous and intranasal administration

PurposeTuberculosis, a cost and life threatening disease, was being subjected for improving vaccine strategies beyond BCG. Thus, a novel particulate delivery system using alginate-coated chitosan nanoparticles including PPE17 protein and CpG were administered through intranasal (IN) and subcutaneous (SC) routes. MethodsThe encapsulated nanoparticles were first characterized for size, surface charge, encapsulation efficiency and in vitro release of PPE17 antigen. The nanoparticles were then administered intranasal and subcutaneously to evaluate the induction of systemic and/or mucosal immune responses in mice. ResultsAccording to our result, the mean size of nanoparticles was measured about 427 nm, and exhibited a negative zeta potential of −37 mV. Following subcutaneous and intranasal administration, the results from cytokines assay showed that an increasing in the level of IFN-γ, and adversely a decrease in the level of IL-4 (presumptive Th1 biased immune response) was happened and also a notable elicitation in IL-17 cytokine was observed. ConclusionIn conclusion, our study demonstrated that alginate-coated chitosan nanoparticles showed to be an effective way to improve BCG efficiency as booster strategy for subcutaneous vaccine, and also can induce strong immune responses as prime strategy through intranasal vaccination.

Livelihood Continuity and Change: Adaptation to Climate and Environmental Change in Northern Unguja, Zanzibar 1916-2016

Coastal community continuity and change in livelihoods become a prime adaptation strategy worldwide because of climate and environmental change. The changes in climate and environment along the coast have been associated with natural and human induced factors. This paper analysed the livelihood continuity and change as adaptation measures in northern Unguja, in relation to temperature and rainfall change. Archival and current reviews, interview and observation which represent the livelihoods change over last 100years were used. The paper also, analyzed how local community processes of continuity and change have interconnected with local climate events and changes over last 100 years. The results reveal that there were societal change both North Western Zone and North Eastern Zone in livelihoods activities as an adaptation mechanism due to gradual environmental changes, such as coastal erosion, coastal floods, unreliable rainfall and droughts. Such scenario increases the risk and vulnerability to the local community. The study also reveals that the identification of risks and vulnerability depends on the local community perceptions of what functions the coastal and terrestrial land should provide, as they informed by past experience, histories and current situation. Therefore, the successful adaptation from the local perspective should go beyond protecting what is already there and allow for future development of the village.

Efficacy of Early Post-Transplant Vaccination Using a Prime and Boost Strategy Is Independent of a Prior History of GvHD: Results from BMT CTN 0201

Introduction: BMT CTN 0201 was a randomized trial of bone marrow (BM) vs G-CSF mobilized peripheral blood (G-PB) grafts in 550 patients with leukemia or MDS undergoing allogeneic hematopoietic stem cell transplantation from unrelated donors. Responses to the 23-valent-pneumococcal vaccine are poor in elderly and immune-compromised patients, including allo-transplant recipients. A secondary objective of BMT CTN 0201 compared responses to post-transplant vaccination using protein-based diphtheria-tetanus (dT) vaccine followed by two doses of a diphtheria-pneumococcal polysaccharide conjugate (PCV7) and the 23-valent pneumococcal polysaccharide vaccine (PPV23).Methods: Vaccination started at 6 months post-transplant with dT followed by PCV7 at 7 and 9 months and PPV23 at 11 months post-transplant. Hepatitis B vaccination occurred at 6, 7 and 11 months. Serological responses in BMT CTN 0201 patients surviving to one year post-transplant were compared among those vaccinated per protocol (N=71), those that received partial vaccination (N=58) or no vaccines (N=39). Primary end-points were the fractions of vaccinated individuals with protective antibody titers to the 14 common pneumococcal bacterial serotypes, Hepatitis B, diphtheria and tetanus. Clinical history of acute or chronic GVHD, blood B-cells and T-cells, and serum immunoglobulin levels were studied as covariates of protective immunological responses.Results: Overall survival at 3 years across the cohorts that received full, partial, or no vaccination was similar (81%, 87%, 84%). Lack of compliance with protocol vaccination did not vary according to whether subjects had a history of acute or chronic GVHD. The frequency of patients with prior history of grade 2-4 acute GVHD or chronic GVHD were similar across the three cohorts (82%, 90%, 82%), with comparable rates of severe grades 3-4 acute (10%, 12%, 13%) and extensive chronic GVHD (63%, 67%, 64%, respectively). Serological responses to vaccines did not differ between recipients of BM vs G-PB grafts, or whether patients had a history of grade 2-4 acute GVHD or chronic GVHD. Serological responses were highly associated with protocol-specified vaccination, with median (range) of titers (ug/mL) for fully vaccinated versus non-vaccinated individuals for HepB: 10.81 (0.05-110) versus 0.49 (0.05-63) p=0.01; tetanus, 2.80 (0.16-20) versus 0.40 (0.05-20) p<0.001; diphtheria: 1.62 (0.05-20) versus 0.08 (0.05-1.2) p<0.001; as well as protective antibody titers to each of the component pneumococcal epitopes shared between PCV7 and PPV23 (Table 1, N=71 fully vaccinated and N=48 with no pneumococcal vaccines). Among the fully-vaccinated cohort, a greater proportion had protective antibodies to individual pneumococcal serotypes present in the PCV7 “prime” vaccine (median 66%) versus those restricted to the PPV23 “boost” vaccine (median 41%). Serum levels of IgA, IgM, and IgG at 12 months post-transplant were correlated with the kinetics of B-cell recovery in the blood at 3, 6, and 12 months. Antibody titers to tetanus, diphtheria and 8/14 of the tested pneumococcal serotypes were correlated with total serum IgG levels at 12 months post-transplant. Titers to diphtheria, a T-cell dependent antigen, were correlated with day +100 blood levels of T-cells, myeloid dendritic cells and B-cells (p<0.05), while antibody levels to serotypes in PCV7 were correlated with day +100 levels of B-cells in the blood.Conclusion: The efficacy of vaccination to specific pneumococcal serotypes among recipients of allogeneic transplants is enhanced by priming with dT and PCV7 prior to vaccination with the PPV23 vaccine. Vaccination is effective in patients with a history of acute or chronic GVHD. Strategies that enhance B-cell recovery post-transplant may improve responses to vaccines, especially those that are T-cell independent. [Display omitted] DisclosuresWaller:National Institutes of Health: Research Funding; Helocyte: Consultancy; Chimerix: Equity Ownership; Cerus: Equity Ownership; Coulter Foundation: Research Funding; PRA: Consultancy; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Research Funding; Cambium Medical Technologies: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Katz Foundation: Research Funding; AMGEN: Consultancy; Celldex: Consultancy.