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1.
Indian J Med Res ; 155(5&6): 451-460, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35975352

RESUMEN

Background & objectives: Globally, vaccination is considered as an important public health strategy to mitigate the impact of the COVID-19 pandemic. The purpose of the current study was to conduct an in-depth inquiry to explore perceptions of community members around COVID-19 vaccines in the southern city of Chennai, Tamil Nadu. This was conducted during the early phase of the vaccine rollout programme in India. Methods: A qualitative investigation was conducted between January-February 2021 through in-depth interviews. Healthcare workers, religious leaders, community influencers, local administrators and representatives of marginalized communities were included. The key informant interview guides and probes explored five domains; (i) vaccine availability, (ii) trust in COVID-19 vaccines, (iii) vaccine-related concerns, (iv) health/risk balance and (v) vaccine prioritization. Transcripted interviews were coded using a thematic approach and analyzed manually as well as with the help of ATLAS.ti 9 software. Results: Eagerness to receive COVID-19 vaccines amongst some of the respondents was linked with freedom from fear, possible restoration of normalcy, protection of family and ability to travel and work abroad. Concerns around threat of emergence of new variants, damage caused by such viral mutants and trust in policymakers were other facilitatory influencers for vaccine uptake. On the other hand, doubts surrounding safety and fear of side effects of COVID-19 vaccine were the feeders to vaccine hesitancy. Lack of accurate information, sensational media reports and rumours exacerbated this fear and provoked anxiety among people. Apprehensions around COVID-19 vaccine in the wake of its rapid development and approval for use and reluctance to take it during the declining phase of the epidemic were identified as other inhibitory factors. Participants underlined the importance of having responsive communication strategies in place focussing on vaccine safety. Making vaccines available to people free of cost and ensuring wider access were other programmatic suggestions. Interpretation & conclusions: In conclusion, our study findings suggest that it is essential to remain engaged with communities and execute evidence-based information dissemination strategy about the safety and efficacy of the vaccines. We identified that it is also imperative to sensitize and train media professionals on how to report side effects related to vaccines. Responsive communication strategies will thus have the potential to serve as a key public health approach pertaining to future pandemic preparedness as well as to manage the demands of clinical and public health issues in an ongoing pandemic situation.


Asunto(s)
COVID-19 , Vacunas , Humanos , Vacunas contra la COVID-19/efectos adversos , Pandemias/prevención & control , India/epidemiología , Investigación Cualitativa , COVID-19/epidemiología , COVID-19/prevención & control , Vacunación
2.
Environ Health ; 20(1): 120, 2021 11 19.
Artículo en Inglés | MEDLINE | ID: mdl-34794454

RESUMEN

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic poses a serious public health concern worldwide. Certain regions of the globe were severely affected in terms of prevalence and mortality than other. Although the cause for this pattern is not clearly understood, lessons learned from previous epidemics and emerging evidences suggest the major role of ecological factors like ambient air pollutants (AAP) and meteorological parameters in increased COVID-19 incidence. The present study aimed to understand the impact of these factors on SARS-CoV-2 transmission and their associated mortality in major cities of India. METHODS: This study used secondary AAP, meteorological and COVID-19 data from official websites for the period January-November 2020, which were divided into Pre-lockdown (January-March 2020), Phase I (April to June 2020) and Phase II (July to November 2020) in India. After comprehensive screening, five major cities that includes 48 CPCB monitoring stations collecting daily data of ambient temperature, particulate matter PM2.5 and 10 were analysed. Spearman and Kendall's rank correlation test was performed to understand the association between SARS-CoV-2 transmission and AAP and, meteorological variables. Similarly, case fatality rate (CFR) was determined to compute the correlation between AAP and COVID-19 related morality. RESULTS: The level of air pollutants in major cities were significantly reduced during Phase I compared to Pre-lock down and increased upon Phase II in all the cities. During the Phase II in Delhi, the strong significant positive correlation was observed between the AAP and SARS-CoV-2 transmission. However, in Bengaluru, Hyderabad, Kolkata and Mumbai AAP levels were moderate and no correlation was noticed. The relation between AT and SARS-CoV-2 transmission was inconclusive as both positive and negative correlation observed. In addition, Delhi and Kolkata showed a positive association between long-term exposure to the AAP and COVID-19 CFR. CONCLUSION: Our findings support the hypothesis that the particulate matter upon exceeding the satisfactory level serves as an important cofactor in increasing the risk of SARS-CoV-2 transmission and related mortality. These findings would help public health experts to understand the SARS-CoV-2 transmission against ecological variables in India and provides supporting evidence to healthcare policymakers and government agencies for formulating strategies to combat the COVID-19.


Asunto(s)
Contaminantes Atmosféricos , COVID-19 , Conceptos Meteorológicos , Contaminantes Atmosféricos/análisis , COVID-19/mortalidad , COVID-19/transmisión , Ciudades , Monitoreo del Ambiente , Humanos , India/epidemiología , Material Particulado/análisis
3.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21263807

RESUMEN

With increasing demand for large numbers of testing during COVID-19 pandemic, came alternative protocols with shortened turn-around time. We evaluated the performance of such an approach wherein 1138 consecutive clinic attendees were enrolled; 584 and 554 respectively from two independent study sites in the cities of Pune and Kolkata. Paired nasopharyngeal and oropharyngeal swabs were tested by using both reference and index methods in blinded fashion. Prior to conducting RT-PCR, swabs collected in viral transport medium (VTM) were processed for RNA extraction (reference method) and swabs collected in dry tube without VTM were incubated in Tris-EDTA-Proteinase K buffer for 30 minutes and heat inactivated at 98{degrees}C for 6 minutes (index method). Overall sensitivity and specificity of the index method were 78.9% (95% CI 71% to 86%) and 99 % (95% CI 98% to 99.6%) respectively. Agreement between the index and reference method was 96.8 % (k = 0.83, SE=0.030). The reference method exhibited enhanced detection of viral genes (E, N and RdRP) with lower Ct values compared to the index method. The index method can be used for detecting SARS-CoV-2 infection with appropriately chosen primer-probe set and heat treatment approach in pressing time; low sensitivity constrains its potential wider use.

4.
Curr Treat Options Infect Dis ; 13(1): 14-31, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33519303

RESUMEN

PURPOSE OF REVIEW: There is a need for enhanced adoption of infection prevention and control (IPC) practices in both healthcare settings and the entire community, more so during pandemics. The exponential increase in the use of social media (SM) has made it a powerful tool for creating awareness, education, training and community engagement on IPC. Here, we review how social media can be used effectively to implement strategies to combat public health issues especially vis-à-vis infection prevention and control. RECENT FINDINGS: According to the World Health Organization, 10% of patients get an infection whilst receiving care in healthcare institutions. Effective infection prevention and control measures can reduce healthcare-associated infections by at least 30%. Education and awareness play a vital role in implementation of infection prevention and control (IPC) strategies. Various studies show how social media has been used successfully in education and training activities, for awareness campaigns, community engagement, risk communications during outbreaks, disease surveillance and pharmacovigilance. SUMMARY: Infection prevention and control (IPC) is the need of the hour to mitigate transmission of disease in healthcare settings as well as in the community. SM is the fastest and most efficient way of communicating with the general population as well as health professionals. SM can help people take the right decisions and enable change in their behaviour patterns to introduce infection control practices.

5.
Indian J Med Res ; 149(2): 164-179, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-31219080

RESUMEN

The Indian Council of Medical Research, in 2013, initiated the Antimicrobial Resistance Surveillance & Research Network (AMRSN) to enable compilation of data on six pathogenic groups on antimicrobial resistance from the country. The overarching aim of this network was to understand the extent and pattern of antimicrobial resistance (AMR) and use this evidence to guide strategies to control the spread of AMR. This article describes the conception and implementation of this AMR surveillance network for India. Also described are the challenges, limitations and benefits of this approach. Data from the Network have shown increasing resistance in Gram-negative bacteria in the hospitals that are part of this network. Combined resistance to third-generation cephalosporins and fluoroquinolones and increasing carbapenem resistance are worrisome, as it has an important bearing on the patients' outcome and thus needs to be addressed urgently. Data generated through this Network have been used to develop treatment guidelines, which will be supportive in harmonizing treatment practices across the tertiary level healthcare institutions in the country. While, the major benefit of having a surveillance system is the collection of real-time accurate data on AMR including the mechanisms of resistance, representativeness to community, sustaining the current effort and expanding the current activities to next levels of healthcare settings are the major challenges. The data emanating from the network besides providing evidence, expose several gaps and lacunae in the ecosystem and highlight opportunities for action by multiple stakeholders.


Asunto(s)
Infecciones Bacterianas/epidemiología , Farmacorresistencia Bacteriana Múltiple/genética , Bacterias Gramnegativas/efectos de los fármacos , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Infecciones Bacterianas/genética , Infecciones Bacterianas/microbiología , Fluoroquinolonas/efectos adversos , Fluoroquinolonas/uso terapéutico , Bacterias Gramnegativas/patogenicidad , Humanos , India/epidemiología , Pruebas de Sensibilidad Microbiana
6.
Indian J Med Res ; 149(2): 180-184, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-31219081

RESUMEN

Antimicrobial resistance (AMR) in India has become a great threat because of high rate of infectious diseases. One of the key contributing factors is high antibiotic use due to poor prescription practices, self-medication, over-the-counter sale of drugs and lack of awareness. Antimicrobial stewardship programme (AMSP) have been proved to be successful in restraining sale and use of antibiotics to a large extent in many countries. An AMSP programme for a hospital is imperative for rational and evidence-based antimicrobial therapy. The ultimate aim is to improve patient outcomes, reduce emergence of bacterial resistance and ensure longevity of the existing antimicrobials. The primary goal of AMSP is to encourage cautious use of available antibiotics by training the healthcare workers and creating awareness. This article describes the strategies and recommendations for formulation of AMSP policy for India.


Asunto(s)
Antibacterianos/efectos adversos , Antiinfecciosos/efectos adversos , Infecciones Bacterianas/epidemiología , Salud Pública/legislación & jurisprudencia , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos/legislación & jurisprudencia , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Humanos , India/epidemiología
7.
Biochem Biophys Res Commun ; 505(4): 979-984, 2018 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-30297111

RESUMEN

The notoriety of parasitic nematode survival is directly related to chronic pathogenicity, which is evident in human lymphatic filariasis. It is a disease of poverty which causes severe disability affecting more than 120 million people worldwide. These nematodes down-regulate host immune system through a myriad of strategies that includes secretion of antioxidant and detoxification enzymes like glutathione-S-transferases (GSTs). Earlier studies have shown Wuchereria bancrofti GST to be a potential therapeutic target. Parasite GSTs catalyse the conjugation of glutathione to xenobiotic and other endogenous electrophiles and are essential for their long-term survival in lymph tissues. Hence, the crystal structure of WbGST along with its cofactor GSH at 2.3 Šresolution was determined. Structural comparisons against host GST reveal distinct differences in the substrate binding sites. The parasite xenobiotic binding site is more substrate/solvent accessible. The structure also suggests the presence of putative non-catalytic binding sites that may permit sequestration of endogenous and exogenous ligands. The structure of WbGST also provides a case for the role of the π-cation interaction in stabilizing catalytic Tyr compared to stabilization interactions described for other GSTs. Hence, the obtained information regarding crucial differences in the active sites will support future design of parasite specific inhibitors. Further, the study also evaluates the inhibition of WbGST and its variants by antifilarial diethylcarbamazine through kinetic assays.


Asunto(s)
Filariasis Linfática/tratamiento farmacológico , Glutatión Transferasa/química , Glutatión Transferasa/metabolismo , Wuchereria bancrofti/enzimología , Animales , Sitios de Unión/efectos de los fármacos , Cristalografía por Rayos X , Dietilcarbamazina/farmacología , Filariasis Linfática/metabolismo , Glutatión Transferasa/antagonistas & inhibidores , Humanos , Cinética , Modelos Moleculares , Wuchereria bancrofti/efectos de los fármacos
8.
Stem Cell Res ; 19: 65-75, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28076753

RESUMEN

Chemotherapy resistant leukemic stem cells (LSCs) are being targeted as a modern therapeutic approach to prevent disease relapse. LSCs isolated from methotrexate resistant side population (SP) of leukemic cell lines HL60 and MOLT4 exhibited high levels of CD25 and TRAIL R2/DR5 which are potential targets. Recombinant immunotoxin conjugating IL2α with TRAIL peptide mimetic was constructed for DR5 receptor specific targeting of LSCs and were tested in total cell population and LSCs. IL2-TRAIL peptide induced apoptosis in drug resistant SP cells from cell lines and showed potent cytotoxicity in PBMCs derived from leukemic patients with an efficacy of 81.25% in AML and 100% in CML, ALL and CLL. IL2-TRAIL peptide showed cytotoxicity in relapsed patient samples and was more effective than TRAIL or IL2-TRAIL proteins. Additionally, DR5 specific IL2-TRAIL peptide was effective in targeting and killing LSCs purified from cell lines [IC50: 952nM in HL60, 714nM in MOLT4] and relapsed patient blood samples with higher efficacy (85%) than IL2-TRAIL protein (46%). Hence, CD25 and DR5 specific targeting by IL2-TRAIL peptide may be an effective strategy for targeting drug resistant leukemic cells and LSCs.


Asunto(s)
Apoptosis/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Leucemia/patología , Células Madre Neoplásicas/metabolismo , Péptidos/toxicidad , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/química , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Células HL-60 , Humanos , Inmunotoxinas/genética , Inmunotoxinas/metabolismo , Inmunotoxinas/toxicidad , Interleucina-2/genética , Interleucina-2/metabolismo , Interleucina-2/toxicidad , Subunidad alfa del Receptor de Interleucina-2/antagonistas & inhibidores , Subunidad alfa del Receptor de Interleucina-2/genética , Leucemia/tratamiento farmacológico , Leucemia/metabolismo , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Metotrexato/uso terapéutico , Metotrexato/toxicidad , Microscopía Fluorescente , Células Madre Neoplásicas/citología , Péptidos/genética , Péptidos/metabolismo , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/genética , Recurrencia
9.
Target Oncol ; 11(4): 535-47, 2016 08.
Artículo en Inglés | MEDLINE | ID: mdl-26984209

RESUMEN

BACKGROUND: Human TNF-related apoptotic-inducing ligand (TRAIL) has been used successfully for targeted therapy of almost all cancers. Leukemia is the most common type of cancer in children, and despite the advances in therapeutic strategies, the survival rate in leukemia cases is very low. Overexpression of interleukin 2 receptor (IL2R) in hematological malignancies has been utilized to target leukemia. Here, we report an immunotoxin fusion construct of human IL2α and TRAIL for targeting leukemia. AIM: Our aim was to develop an immunotoxin to target CD25+ leukemic cells. METHODS: Recombinant fusion construct comprising human IL2α and TRAIL114-281 was cloned, expressed and purified. Surface expression levels of IL2α and TRAIL receptors (CD25 and DR5 respectively) were compared in four leukemic cell lines and patient-derived peripheral blood mononuclear cells (PBMCs). Efficacy of immunotoxins was tested in cell lines and PBMCs by cell viability assay and compared with receptor expression. RESULTS: The efficacy of IL2-TRAIL was higher than TRAIL alone and showed an IC50 ranging from 0.2-0.8 µM in cell lines. IL2-TRAIL induced cell death in PBMCs from leukemic patients in vitro, which was proportional to CD25 expression. Out of 34 leukemic samples, 24 samples were susceptible to immunotoxin-mediated cytotoxicity. The efficacy of IL2-TRAIL (87.5 %) was significantly high compared to TRAIL protein (29 %) in both myeloid and lymphoid leukemic patient samples. IL2-TRAIL fusion protein was highly specific for CD25+ leukemia and showed 100 % efficacy in lymphocytic leukemia [acute lymphoblastic leukemia and chronic lymphocytic leukemia] that overexpressed CD25.


Asunto(s)
Subunidad alfa del Receptor de Interleucina-2/genética , Leucemia/genética , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Proliferación Celular , Humanos , Inmunotoxinas/farmacología , Leucemia/patología
10.
Drug Discov Today ; 21(2): 325-32, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26049016

RESUMEN

The identification of numerous unique targets in recent years has led to the development of various immunotoxins (ITs) for treating hematological malignancies. Some of these ITs have advanced to clinical trials and have resulted in a high response rate against leukemia. Newer targets with improve specificity are also being identified for targeting several leukemias. Currently, several modified versions of ITs with increased efficacy are being constructed and evaluated for cytotoxicity in vitro as well as in vivo. Here, we summarize recent advances in preclinical and clinical studies of recombinant ITs targeting diverse surface receptors.


Asunto(s)
Neoplasias Hematológicas/tratamiento farmacológico , Inmunotoxinas/uso terapéutico , Animales , Humanos , Ligandos
11.
Eur J Pharmacol ; 747: 174-80, 2015 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-25514604

RESUMEN

Modern recombinant vaccines are less immunogenic than conventional vaccines which require adjuvants to enhance the effect of a vaccine. Alum is being used as a standard adjuvant for protein based vaccines to augment immune response in several diseases. However, the problem associated with alum is it requires multiple doses at specific time intervals to achieve the adequate level of immunity. Currently the adjuvanticity of Poly-l-lactide microparticles as single dose immunization was explored to overcome multiple immunization and reported to be effective for several diseases. In this regard we adsorbed filarial recombinant chimeric multivalent vaccine candidates such as TV and FEP on to PLA by double emulsion method and analyzed the characterization of PLA encapsulated microparticles and evaluated its immune responses in mice. The efficacy of single dose of PLA encapsulated proteins was investigated in comparison with single dose of alum or protein alone. In mice, single dose of PLA encapsulated antigens such as TV and FEP elicited significantly high antibody titer of 50,000 and 64,000 respectively than single dose of alum adsorbed TV/FEP (6000/9000) and single dose of protein TV/FEP (3000/4000) alone. Further PLA encapsulated antigens induced higher levels of cellular proliferation together with significant (P<0.0001) levels of cytokine response [PLA-TV induced high levels of IL-4(Th2) and IFN-γ (Th1) cytokines whereas PLA-FEP showed high levels of IL-5(Th2) and IFN-γ (Th1)] indicating a balanced response elicited by PLA antigens. Overall strong humoral and cellular responses were observed for PLA encapsulated antigens compared with single dose of alum adsorbed or protein alone.


Asunto(s)
Antígenos/química , Antígenos/inmunología , Portadores de Fármacos/química , Microesferas , Poliésteres/química , Vacunas/química , Vacunas/inmunología , Adyuvantes Inmunológicos/química , Adsorción , Animales , Proliferación Celular , Citocinas/metabolismo , Preparaciones de Acción Retardada , Portadores de Fármacos/metabolismo , Filariasis Linfática/prevención & control , Epítopos/inmunología , Ratones , Poliésteres/metabolismo , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/inmunología , Bazo/citología , Bazo/inmunología
12.
Acta Parasitol ; 59(3): 454-8, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25119360

RESUMEN

Transmission of lymphatic filariasis is mediated through microfilariae (L1 stage of the parasite) which is encased in an eggshell called sheath. The sheath protein Shp-1 stabilizes the structure due to the unique repeat region with Met-Pro-Pro-Gln-Gly sequences. Microfilarial proteins could be used as transmission blocking vaccines. Since the repeat region of Shp-1 was predicted to carry putative B epitopes, this region was used to analyze its reactivity with clinical samples towards construction of peptide vaccine. In silico analysis of Shp-1 showed the presence of B epitopes in the region 49-107. The polypeptide epitopic region Shp-149-107 was cloned and expressed in Escherichia coli. Antibody reactivity of the Shp-149-107 construct was evaluated in filarial endemic population by ELISA. Putatively immune endemic normals (EN) showed significantly high reactivity (P < 0.05) when compared to all the other categories. Antibody reactivity of Shp-1 repeat region was similar to that of whole protein proving that this region carries B epitopes responsible for its humoral response in humans. Thus this can be employed for inducing anti-microfilarial immunity in the infected population that may lead to reduction in transmission intensity and also it could be used along with other epitopes from different stages of the parasite in order to manage the disease effectively.


Asunto(s)
Anticuerpos Antihelmínticos/sangre , Antígenos Helmínticos/inmunología , Brugia Malayi/inmunología , Filariasis Linfática/inmunología , Proteínas del Helminto/inmunología , Animales , Filariasis Linfática/parasitología , Ensayo de Inmunoadsorción Enzimática , Epítopos , Humanos , Microfilarias
13.
Vet Microbiol ; 171(1-2): 13-22, 2014 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-24745626

RESUMEN

Infectious Bursal Disease Virus (IBDV) causes immunosuppression in young chickens by destruction of antibody producing B cells in the Bursa of Fabricius and poses a potential threat to the poultry industry. We have examined the protective efficacy of a subunit DNA vaccine against IBDV infection in chickens in this study. An immunodominant VP2 gene fragment (VP252-417) was cloned into CMV promoter based DNA vaccine vector pVAX1 and in vitro expression of the DNA encoded antigens was confirmed by transfection of CHO cells with vaccine constructs followed by RT-PCR and western blot analysis using IBDV-antiserum. Two weeks old chickens were immunized intramuscularly with pVAXVP252-417 and the in vivo transcription of the plasmid DNA was confirmed by RT-PCR analysis of DNA injected muscle tissue at different intervals of post immunization. Tissue distribution analysis revealed that the plasmid DNA was extensively distributed in muscle, spleen, kidney, liver, and bursa tissues. Chickens immunized with pVAXVP252-417 developed high titer (1:12,000) of anti-VP252-417 antibodies. Further, chicken splenocytes from pVAXVP252-417 immunized group showed a significantly high proliferation to the whole viral and recombinant antigen (P<0.01) compared to control groups, which implies that pVAXVP252-417 codes for immunogenic fragment which has epitopes capable of eliciting both B and T cell responses. This is evident by the fact that, pVAXVP252-417 immunized chicken conferred 75% protection against virulent IBDV (vIBDV) challenge compared to the control group. Thus, the present study confirms that the immunodominant VP2 fragment can be used as a potential DNA vaccine against IBDV infection in chickens.


Asunto(s)
Infecciones por Birnaviridae/veterinaria , Proteínas de la Cápside/genética , Enfermedades de las Aves de Corral/prevención & control , Vacunación/veterinaria , Vacunas Virales/inmunología , Animales , Anticuerpos Antivirales/sangre , Infecciones por Birnaviridae/mortalidad , Infecciones por Birnaviridae/prevención & control , Bolsa de Fabricio/inmunología , Células CHO , Pollos , Cricetulus , Inmunidad Celular , Inmunidad Humoral/inmunología , Virus de la Enfermedad Infecciosa de la Bolsa/genética , Virus de la Enfermedad Infecciosa de la Bolsa/inmunología , Músculo Esquelético/química , Plásmidos/análisis , Enfermedades de las Aves de Corral/inmunología , Enfermedades de las Aves de Corral/mortalidad , Organismos Libres de Patógenos Específicos , Análisis de Supervivencia , Linfocitos T/inmunología , Vacunas de ADN/inmunología
14.
Acta Parasitol ; 58(4): 468-77, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24338307

RESUMEN

Although multiple vaccine strategy for lymphatic filariasis has provided tremendous hope, the choice of antigens used in combination has determined its success in the previous studies. Multiple antigens comprising key vaccine candidates from different life cycle stages would provide a promising strategy if the antigenic combination is chosen by careful screening. In order to analyze one such combination, we have used a chimeric construct carrying the well studied B. malayi antigens thioredoxin (BmTRX) and venom allergen homologue (BmVAH) as a fusion protein (TV) and evaluated its immune responses in mice model. The efficacy of fusion protein vaccine was explored in comparison with the single antigen vaccines and their cocktail. In mice, TV induced significantly high antibody titer of 1,28,000 compared to cocktail vaccine TRX+VAH (50,000) and single antigen vaccine TRX (16,000) or VAH (50,000). Furthermore, TV elicited higher level of cellular proliferative response together with elevated levels of IFN-γ, IL-4 and IL-5 indicating a Th1/Th2 balanced response. The isotype antibody profile showed significantly high level of IgG1 and IgG2b confirming the balanced response elicited by TV. Immunization with TV antigen induced high levels of both humoral and cellular immune responses compared to either cocktail or antigen given alone. The result suggests that TV is highly immunogenic in mice and hence the combination needs to be evaluated for its prophylactic potential.


Asunto(s)
Antígenos Helmínticos/inmunología , Brugia Malayi/inmunología , Filariasis Linfática/prevención & control , Proteínas del Helminto/administración & dosificación , Tiorredoxinas/inmunología , Animales , Anticuerpos Antihelmínticos/sangre , Antígenos Helmínticos/administración & dosificación , Antígenos Helmínticos/genética , Brugia Malayi/enzimología , Brugia Malayi/genética , Proliferación Celular , Filariasis Linfática/inmunología , Proteínas del Helminto/genética , Inmunoglobulina G/sangre , Interferón gamma/metabolismo , Interleucina-4/metabolismo , Interleucina-5/metabolismo , Leucocitos Mononucleares/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/inmunología , Tiorredoxinas/genética , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunología
15.
Vet Immunol Immunopathol ; 148(3-4): 293-301, 2012 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-22795186

RESUMEN

Infectious bursal disease virus (IBDV) is the causative agent of Gumboro disease and poses a huge threat to poultry industry. The risks associated with conventional attenuated viral vaccines make it indispensable to probe into the development of novel and rationally designed subunit vaccines which are safer as well as effective. VP2 is the major host-protective antigen found in IBDV capsid. It encompasses different independent epitopes responsible for the induction of neutralizing antibody. Here, we report the efficacy of the immunodominant fragment of VP2 which induces both humoral and cellular immunity against infectious bursal disease. A 366 bp fragment (52-417 bp) of the VP2 gene from an IBDV field isolate was amplified and expressed in Escherichia coli as a 21 kDa recombinant protein. The efficacy of rVP2(52-417) antigen was compared with two commercial IBDV whole virus vaccine strains. The rVP2(52-417) induced significantly high antibody titres in chicken compared to commercial vaccines and the anti-rVP2(52-417) sera showed reactivity with viral antigens from both commercial strains (P<0.0001) and field isolates. Also, the chicken splenocytes from rVP2(52-417) immunized group showed a significantly high proliferation (P<0.01) compared to other groups, which implies that the rVP2(52-417) fragment contains immunogenic epitopes capable of eliciting both B and T cell responses. Further, rVP2(52-417) conferred 100% protection against vIBDV challenge in the immunized chickens which was significantly higher (P<0.001) compared to 55-60% protection by commercial vaccine strains. Hence, the study confirms the efficacy of the immunodominant VP2 fragment that could be used as a potent vaccine against IBDV infection in chicken.


Asunto(s)
Infecciones por Birnaviridae/veterinaria , Virus de la Enfermedad Infecciosa de la Bolsa/inmunología , Enfermedades de las Aves de Corral/virología , Proteínas Estructurales Virales/inmunología , Vacunas Virales/inmunología , Animales , Anticuerpos Antivirales/inmunología , Infecciones por Birnaviridae/inmunología , Infecciones por Birnaviridae/prevención & control , Pollos/inmunología , Pollos/virología , Inmunidad Celular/efectos de los fármacos , Inmunidad Celular/inmunología , Inmunidad Humoral/efectos de los fármacos , Inmunidad Humoral/inmunología , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunología , Enfermedades de las Aves de Corral/inmunología , Enfermedades de las Aves de Corral/prevención & control , Linfocitos T/inmunología , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/uso terapéutico , Proteínas Estructurales Virales/uso terapéutico , Vacunas Virales/uso terapéutico
16.
Clin Chim Acta ; 412(19-20): 1867-73, 2011 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-21741373

RESUMEN

BACKGROUND: Lymphatic filariasis is a painful and profoundly disfiguring disease. Infection is usually acquired in childhood but its visible manifestations occur later in life, causing temporary or permanent disability. The importance of developing effective assays to diagnose, monitor and evaluate human lymphatic filariasis has been emphasized by the WHO. METHODS: High-affinity monoclonal antibodies (mAbs) specific for recombinant filarial antigen WbSXP-1 were developed. An ELISA based capture assay using monoclonal and polyclonal antibodies for WbSXP-1 was used for detection of circulating filarial antigen. RESULTS: High-affinity monoclonal antibodies (mAbs) were developed that specifically binds both W. bancrofti and B. malayi mf antigens. Two mAbs (1F6H3 and 2E12E3) of subclass IgG2a and IgM showed high affinity, avidity and reactivity to recombinant and mf native antigen. Both the mAbs were used in combination as capture antibodies and polyclonal as detection antibody to develop the assay. The assay showed very high sensitivity towards W. bancrofti mf positive samples compared to endemic normal samples (P<0.0001). CONCLUSION: A capture assay using high-affinity monoclonal antibodies for WbSXP-1 was developed for the detection of filarial circulating antigen in clinical samples from bancroftian infection. Besides, this would also help in epidemiological studies in endemic areas of filarial infections.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Filariasis Linfática/diagnóstico , Ensayo de Inmunoadsorción Enzimática/métodos , Western Blotting , Cromatografía de Afinidad , Humanos
17.
Microbes Infect ; 13(6): 602-6, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21288496

RESUMEN

Although the antioxidant thioredoxin peroxidase (TPX) is a putative target exploited in vaccine studies of lymphatic filariasis, the high sequence homology with host peroxiredoxins remains a great concern. The emergence of immunomics offers a powerful tool for novel vaccine design. Further, due to the cellular hypo-response in filariasis, analysis of T epitope repertoire becomes imperative in disease control. Here, we report the cellular responses of filarial TPX-1 and the identification of T epitope (29-43) in the host non-homologous region. The strong proliferative responses induced by the peptide mimetic in mice splenocytes and human PBMC's prove the existence of T epitope recognized in endemic population.


Asunto(s)
Antígenos Helmínticos/inmunología , Brugia Malayi/inmunología , Filariasis Linfática/inmunología , Filariasis Linfática/parasitología , Epítopos de Linfocito T/inmunología , Peroxirredoxinas/inmunología , Animales , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C
18.
J Parasitol ; 96(6): 1228-9, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21158641

RESUMEN

Filarial thiordoxin peroxidase is a major antioxidant that plays a crucial role in parasite survival. Although Brugia malayi TPx has been shown to be a potential vaccine candidate, it shares 63% homology with its mammalian counterpart, limiting its use as a vaccine or drug target. In silico analysis of TPx sequence revealed a linear B epitope in the host's nonhomologous region. The peptide sequence (TPx peptide(27-48)) was synthesized, and its reactivity with clinical sera from an endemic region was analyzed. The peptide showed significantly high reactivity (P < 0.05) against the sera of putatively immune individuals compared to the nonendemic control sera. It also showed high reactivity against the sera of patients with chronic pathology and patent infection. The high reactivity of the peptide with endemic immune sera equivalent to that of whole protein shows that it forms a dominant B epitope of TPx protein and thus could be utilized for incorporation into a multiepitope vaccine construct for filariasis.


Asunto(s)
Brugia Malayi/enzimología , Filariasis Linfática/inmunología , Sueros Inmunes/inmunología , Peroxirredoxinas/inmunología , Animales , Brugia Malayi/inmunología , Filariasis Linfática/sangre , Filariasis Linfática/parasitología , Enfermedades Endémicas , Epítopos de Linfocito B/inmunología , Humanos , Péptidos/química , Péptidos/inmunología , Peroxirredoxinas/química , Peroxirredoxinas/aislamiento & purificación , Proteínas Recombinantes/química , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/aislamiento & purificación , Vacunas/inmunología
19.
Vaccine ; 28(31): 5038-48, 2010 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-20653106

RESUMEN

Although multi-epitope vaccines have been evaluated for various diseases, they have not yet been investigated for lymphatic filariasis. Here, we report for the first time identification of two immunodominant B epitopes (TRXP1 and TRXP2) from the antioxidant Brugia malayi thioredoxin by studying their immune responses in mice model and human subjects. TRXP1 was also found to harbor a T epitope recognized by human PBMCs and mice splenocytes. Further, the epitopic peptides were synthesized as a single peptide conjugate (PC1) and their prophylactic efficacy was tested in a murine model of filariasis with L3 larvae. PC1 conferred a significantly high protection (75.14%) (P < 0.0001) compared to control (3.7%) and recombinant TRX (63.03%) (P < 0.018) in experimental filariasis. Our results suggest that multi-epitope vaccines could be a promising strategy in the control of lymphatic filariasis.


Asunto(s)
Brugia Malayi/inmunología , Filariasis Linfática/prevención & control , Epítopos de Linfocito B/inmunología , Tiorredoxinas/inmunología , Vacunas Conjugadas/inmunología , Animales , Anticuerpos Antihelmínticos/sangre , Proliferación Celular , Citocinas/inmunología , Filariasis Linfática/inmunología , Epítopos de Linfocito T/inmunología , Femenino , Humanos , Epítopos Inmunodominantes/inmunología , Inmunoglobulina G/sangre , Masculino , Ratones , Ratones Endogámicos BALB C , Murinae , Linfocitos T/inmunología
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