Virology & Mycology Infectious Diseases
 
   Publications A-Z
A
»Accounting & Marketing
» Addiction Research & Therapy
» Advanced Chemical Engineering
»Advances in Automobile Engineering
»Advances in Crop Science and Technology
»Advances in Dairy Research
»Advancements in Genetic Engineering
»Advances in Pharmacoepidemiology & Drug Safety
»Advances in Robotics & Automation
»Advanced Techniques in Biology & Medicine
»Advance Research in Meteorological Sciences
»Aeronautics & Aerospace Engineering
»Aging Science
»Agrotechnology
»AIDS & Clinical Research
»Alcoholism and Drug Dependence
»Allergy & Therapy
»Alternative & Integrative Medicine
»Air & Water borne Diseases
»Alzheimers Disease & Parkinsonism
»Analytical & Bioanalytical Techniques
»Anaplastology
»Anatomy & Physiology
»Ancient Diseases & Preventive Remedies
»Andrology-Open Access
»Anesthesia & Clinical Research
»Angiology: Open Access
»Antivirals & Antiretrovirals
»Anthropology
»Applied & Computational Mathematics
»Applied Mechanical Engineering
»Aquaculture Research & Development
» Arabian Journal Business and Management Review
»Architectural Engineering Technology
»Arthritis
»Arts and Social Sciences Journal
» Astrobiology & Outreach
»Astrophysics & Aerospace technology
»Autacoids
»Automatic Control of Physiological State and Function
»Autism-Open Access
  
B
»Bacteriology & Parasitology
»Bioanalysis & Biomedicine
»Bioceramics Development and Applications
»Biochemistry and Analytical Biochemistry
»Biochemistry & Pharmacology: Open Access
»Biochips & Tissue Chips
»Biodiversity & Endangered Species
»Bioenergetics: Open Access
»Bioengineering & Biomedical Science
»Bioequivalence & Bioavailability
»Biosafety & Health Education
»Biofertilizers & Biopesticides
»Biometrics & Biostatistics
»Biomimetics Biomaterials and Tissue Engineering
»Biomolecular Research & Therapeutics
» Biomusical Engineering
»Biochemistry & Physiology: Open Access
»Biological Systems- Open Access
»Biology and Medicine
»Bioprocessing & Biotechniques
»Bioremediation & Biodegradation
»Biosafety
»Biosensors & Bioelectronics
» Biosensors Journal
»Biotechnology & Biomaterials
»Bioterrorism & Biodefense
»Blood Disorders & Transfusion
»Blood & Lymph
»Bone Marrow Research
»Brain Disorders & Therapy
»Business and Economics Journal
»Business and Financial Affairs
  
C
»Cancer Science & Therapy
»Climatology & Weather forecasting
»Carcinogenesis & Mutagenesis
»Cardiovascular Diseases & Diagnosis
»Cardiovascular Pharmacology: Open Access
»Cell & Developmental Biology
»Cell Science & Therapy
»Chemical Engineering & Process Technology
»Chemical Sciences Journal
»Chemotherapy: Open Access
»Child and Adolescent Behavior
»Chromatography & Separation Techniques
»Civil & Environmental Engineering
»Civil & Legal Sciences
»Clinical & Cellular Immunology
»Clinical Case Reports
»Clinical & Experimental Cardiology
»Clinical & Experimental Dermatology Research
»Clinical & Experimental Ophthalmology
»Clinical & Experimental Pathology
»Clinical & Experimental Pharmacology
»Clinical Microbiology: Open Access
»Clinical Pharmacology & Biopharmaceutics
»Clinical Research & Bioethics
»Clinical Research on Foot & Ankle
»Clinical Toxicology
»Clinical Trials
»Clinics in Mother and Child Health
»Cloning & Transgenesis
»Community Medicine & Health Education
»Communication Disorders, Deaf Studies & Hearing Aids
»Computer Science & Systems Biology
» Current Synthetic & Systems Biology
»Cytology & Histology
D
»Data Mining in Genomics & Proteomics
»Defense Management
»Dentistry
»Depression and Anxiety
»Developing Drugs
»Diabetes & Metabolism
»Drug Designing
»Drug Metabolism & Toxicology
  
E
»Earth Science & Climatic Change
»Ecosystem & Ecography
»Endocrinology & Metabolic Syndrome
»Entomology, Ornithology & Herpetology
»Environmental & Analytical Toxicology
»Epidemiology: Open Access
»Emergency Medicine
»Ergonomics
»Electrical & Electronics
»Enzyme Engineering
»Entrepreneurship & Organization Management
  
F
»Family Medicine & Medical Science Research
»Fermentation Technology
»Fertilization: In Vitro - IVF-Worldwide
»Fisheries and Aquaculture Journal
»Fisheries & Livestock Production
»Food Processing & Technology
»Forensic Biomechanics
»Forensic Research
»Forest Research: Open Access
»Fundamentals of Renewable Energy and Applications
»Fungal Genomics & Biology
  
G
»Gastrointestinal & Digestive System
»Genetic Syndromes & Gene Therapy
»Gene Technology
»Generalized Lie Theory and Applications
»Glycobiology
»Glycomics & Lipidomics
»Gynecology& Obstetrics
»General Medicine
»General Practice
»Geography & Natural Disasters
»Geology & Geosciences
»Geophysics & Remote Sensing
»Gerontology & Geriatric Research
»Global Economics
»Global Journal of Technology and Optimization
  
H
»Hair : Therapy & Transplantation
»Hematology & Thromboembolic Diseases
»Health Care : Current Reviews
»Health & Medical Informatics
»Hereditary Genetics
»Homeopathy & Ayurvedic Medicine
»Horticulture
»Hotel & Business Management
»Human Genetics & Embryology
»Hydrology: Current Research
»Hypertension- Open Access
  
I
»Industrial Engineering & Management
»Irrigation and Drainage Systems Engineering
»Infectious Diseases and Therapy
»Information Technology & Software Engineering
»Intellectual Property Rights: Open Access
»Integrative Oncology
»Internal Medicine
»International Journal of Accounting Research
»International Journal of Advanced Innovations, Thoughts & Ideas
»International Journal of Biomedical Data Mining
»International Journal of Economics and Management Science
»International Journal of Sensor Networks and Data Communications
»International Journal of Swarm Intelligence and Evolutionary Computation
»International Journal of waste resources
»International Journal of Genomic Medicine
»International Journal of Physical Medicine & Rehabilitation
»Innovative Energy Policies
»Immunome Research
  
J
»JBR Journal of Interdisciplinary Medicine and Dental Science
»JBR Journal of Clinical Diagnosis and Research
»JBR Journal of Young Scientist
  
L
»Liver
» Leukemia
» Lovotics
  
M
»Marine Science: Research & Development
»Malaria Chemotherapy, Control & Elimination
»Mass Communication & Journalism
»Material Sciences & Engineering
»Medicinal Chemistry
»Medicinal & Aromatic Plants
»Medical Diagnostic Methods
»Medical Microbiology & Diagnosis
»Medical & Surgical Urology
»Membrane Science & Technology
»Metabolic Syndrome
»Metabolomics:Open Access
»Microbial & Biochemical Technology
»Modern Chemistry & Applications
»Molecular Biology
»Molecular Biomarkers & Diagnosis
»Molecular and Genetic Medicine
»Molecular Imaging & Dynamics
»Molecular Pharmaceutics & Organic Process Research
»Mycobacterial Diseases
N
»Natural Products Chemistry & Research
»Nanomedicine & Biotherapeutic Discovery
»Nanomedicine & Nanotechnology
»Neonatal Biology
»Nephrology & Therapeutics
»Neurology & Neurophysiology
»Neuroinfectious Diseases
»Neurological Disorders
»Novel Physiotherapies
»Nuclear Medicine & Radiation Therapy
»Nutrition & Food Sciences
»Nutritional Disorders & Therapy
»Nursing & Care
  
O
»Obesity & Weight Loss Therapy
»Oceanography-Open Access
»Occupational Medicine & Health Affairs
»OMICS Journal of Radiology
»Osteoporosis and Physical Activity
»Oral Health and Dental Management
»Oral Hygiene & Health
»Organic Chemistry: Current Research
»Orthopedic & Muscular System: Current Research
»Otolaryngology
  
P
»Pain & Relief
»Palliative Care & Medicine
»Pancreatic Disorders & Therapy
»Pediatrics & Therapeutics
»Petroleum & Environmental Biotechnology
»Pharmaceutica Analytica Acta
»Pharmaceutical Regulatory Affairs: Open Access
»Pharmacogenomics & Pharmacoproteomics
»Pharmacovigilance
»Physical Chemistry & Biophysics
»Physical Mathematics
»Plant Pathology & Microbiology
»Plant Biochemistry & Physiology
»Pollution Effects & Control
»political Sciences & public affairs
»Poultry, Fisheries & Wildlife Sciences
»Powder Metallurgy & Mining
»Primatology
»Primary Health Care: Open Access
»Probiotics & Health
» Phylogenetics & Evolutionary Biology
»Proteomics & Bioinformatics
»Phylogenetics & Evolutionary Biology
»Psychology & Psychotherapy
»Psychological Abnormalities in Children
»Pulmonary & Respiratory Medicine
  
R
»Reproductive System & Sexual Disorders
»Research and Development
»Review of Public Adminstration and Management
»Rheumatology: Current Research
»Rice Research: Open Access
  
S
» Single Cell Biology
»Sleep Disorders & Therapy
»Socialomics
»Sociology and Criminology-Open Access
»Sports Medicine & Doping Studies
»Spine
»Stem Cell Research & Therapy
»Steroids & Hormonal Science
»Stock & Forex Trading
»Surgery: Current Research
  
T
»Telecommunications System & Management
»Textile Science & Engineering
»Theoretical and Computational Chemistry:Open Access
»Thermodynamics & Catalysis
»Thyroid Disorders & Therapy
»Tissue Science & Engineering
»Translational Medicine
»Transplantation Technologies & Research
»Transcriptomics: Open Access
»Trauma & Treatment
»Tropical Diseases
»Tropical Medicine and Surgery
»Tourism & Hospitality
  
V
»Vaccines & Vaccination
»Vascular Medicine & surgery
»Veterinary Science & Technology
»Virology & Mycology
»Vitamins & Minerals
»Vortex Science and Technology
  
W
»Women's Health Care
  
Y
»Yoga & Physical Therapy
 
   Browse by Subjects
Clinical
» AIDS & Clinical Research
» Anesthesia & Clinical Research
» Angiology
» Cancer Science & Therapy
» Carcinogenesis & Mutagenesis
» Cell Science & Therapy
» Chemotherapy
» Child & Adolescent Behavior
» Clinical & Cellular Immunology
» Clinical Case Reports
» Clinical & Experimental Cardiology
» Clinical & Experimental Dermatology Research
» Clinical & Experimental Ophthalmology
» Clinical & Experimental Pharmacology
» Clinical & Experimental Pathology
» Clinical Microbiology: Open Access
» Clinical Research & Bioethics
» Clinical Research on Foot & Ankle
» Clinical Toxicology
» Clinical Trials
»Clinics in Mother and Child Health
» Communication Disorders, Deaf Studies & Hearing Aids
» Cytology & Histology
» Forensic Research
»Forensic Biomechanics
» Integrative Oncology
»Immunome Research
»JBR Journal of Clinical Diagnosis and Research
» Neurology & Neurophysiology
» Pulmonary & Respiratory Medicine
» Stem Cell Research & Therapy
» Transplantation Technologies & Research
   
Pharmaceutical Sciences
» Advances in Pharmacoepidemiology & Drug Safety
» Alcoholism and Drug Dependence
» Bioanalysis & Biomedicine
» Biochemical Pharmacology
» Bioequivalence & Bioavailability
» Cardiovascular Pharmacology: Open Access
» Clinical Pharmacology & Biopharmaceutics
» Developing Drugs
» Drug Designing
» Drug Metabolism & Toxicology
» Medicinal & Aromatic Plants
» Molecular Pharmaceutics & Organic Process Research
» Pharmaceutica Analytica Acta
» Pharmaceutical Regulatory Affairs
» Pharmacovigilance
» Vaccines & Vaccination
   
Chemistry
» Advanced Chemical Engineering
» Analytical & Bioanalytical Techniques
» Chemical Sciences Journal
» Chromatography & Separation Techniques
» Medicinal Chemistry
» Modern Chemistry & Applications
» Natural Products Chemistry & Research
» Organic Chemistry
» Physical Chemistry & Biophysics
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» Thermodynamics & Catalysis
» Theoretical and Computational Chemistry:Open Access
   
Environmental
» Anthropology
» Aquaculture Research & Development
» Astrobiology & Outreach
» Biodiversity & Endangered Species
» Earth Science & Climatic Change
» Ecosystem & Ecography
» Environmental & Analytical Toxicology
» Fisheries & Livestock Production
»Fundamentals of Renewable Energy and Applications
» Geography & Natural Disasters
» Hydrology: Current Research
»Innovative Energy Policies
»International Journal of waste resources
» Oceanography-Open Access
» Petroleum & Environmental Biotechnology
» Pollution Effects & Control
» Poultry, Fisheries & Wildlife Sciences
   
Omics
» Data Mining in Genomics & Proteomics
»Ergonomics
» Glycomics & Lipidomics
» Health & Medical Informatics
»JBR Journal of Young Scientist
» Metabolomics:Open Access
» OMICS Journal of Radiology
» Pharmacogenomics & Pharmacoproteomics
» Phylogenetics & Evolutionary Biology
» Proteomics & Bioinformatics
» Transcriptomics
   
Life Sciences
» Advanced Techniques in Biology & Medicine
»Advancements in Genetic Engineering
»Advances in Crop Science and Technology
»Advances in Dairy Research
» Aging Science
» Agrotechnology
» Air & Water Borne Diseases
» Antivirals & Antiretrovirals
» Autism-Open Access
» Bacteriology & Parasitology
» Biochemistry & Physiology
» Biochemistry and Analytical Biochemistry
» Bioenergetics
» Bioengineering & Biomedical Science
» Biofertilizers & Biopesticides
» Biological Systems
» Biometrics & Biostatistics
»Biomimetics Biomaterials and Tissue Engineering
» Biomolecular Research & Therapeutics
» Bioremediation & Biodegradation
» Biosafety
» Biosafety & Health Education
» Biosensors & Bioelectronics
» Biosensors Journal
» Biotechnology & Biomaterials
» Bioterrorism & Biodefense
» Cell & Developmental Biology
» Current Synthetic & Systems Biology
» Entomology, Ornithology & Herpetology
» Enzyme Engineering
» Fermentation Technology
» Fertilization: In Vitro - IVF-Worldwide
» Fisheries and Aquaculture Journal
» Forest Research
» Fungal Genomics & Biology
» Gene Technology
» Glycobiology
» Horticulture
» Homeopathy & Ayurvedic Medicine
»International Journal of Swarm Intelligence and Evolutionary Computation
» Marine Science: Research & Development
» Membrane Science & Technology
» Microbial & Biochemical Technology
» Molecular Biology
» Molecular Imaging & Dynamics
» Nanomedicine & Biotherapeutic Discovery
» Nanomedicine & Nanotechnology
» Nutrition & Food Sciences
» Plant Pathology & Microbiology
» Primatology
» Probiotics & Health
» Rice Research: Open Access
» Single Cell Biology
» Sociology and Criminology-Open Access
» Tissue Science & Engineering
» Tropical Diseases
» Veterinary Science & Technology
» Vitamins & Minerals
»Virology & Mycology
   
Engineering
» Advances in Automobile Engineering
» Advances in Robotics & Automation
» Aeronautics & Aerospace Engineering
» Applied & Computational Mathematics
» Applied Mechanical Engineering
» Architectural Engineering Technology
» Astrophysics & Aerospace technology
» Biochips & Tissue Chips
» Bioprocessing & Biotechniques
» Chemical Engineering & Process Technology
» Civil & Environmental Engineering
» Computer Science & Systems Biology
» Electrical & Electronics
» Food Processing & Technology
» Geology and Geosciences
» Geophysics & Remote sensing
»Global Journal of Technology and Optimization
» Industrial Engineering & Management
» Information Technology & Software Engineering
» International Journal of Advance Innovations, Thoughts & Ideas
»International Journal of Sensor Networks and Data Communications
» Irrigation and Drainage Systems Engineering
»Generalized Lie Theory and Applications
» Lovotics
» Material Sciences & Engineering
»Physical Mathematics
» Powder Metallurgy & Mining
» Telecommunications System & Management
» Textile Science & Engineering
»Vortex Science and Technology
   
Medical Sciences
» Addiction Research & Therapy
» Allergy & Therapy
» Alternative & Integrative Medicine
» Alzheimers Disease & Parkinsonism
» Anaplastology
» Anatomy & Physiology
» Ancient Diseases & Preventive Remedies
» Andrology
» Arthritis
» Autacoids
»Automatic Control of Physiological State and Function
» Bioceramics Development and Applications
» Biology and Medicine
» Biomusical Engineering
» Blood & Lymph
» Blood Disorders & Transfusion
» Bone Marrow Research
» Brain Disorders & Therapy
» Cardiovascular Diseases & Diagnosis
» Cloning & Transgenesis
» Community Medicine & Health Education
» Dentistry
» Depression and Anxiety
» Diabetes & Metabolism
» Emergency Medicine
» Endocrinology & Metabolic Syndrome
» Epidemiology: Open Access
» Family Medicine & Medical Science Research
» Gastrointestinal & Digestive System
» General Medicine
» General Practice
» Genetic Syndromes & Gene Therapy
» Gynecology& Obstetrics
» Gerontology & Geriatrics Research
» Hematology & Thromboembolic Diseases
» Hair: Therapy & Transplantation
» Health Care : Current Reviews
» Hereditary Genetics
» Human Genetics & Embryology
» Hypertension-Open Access
» Infectious Diseases & Therapy
» International Journal of Genomic Medicine
» Internal Medicine
»International Journal of Biomedical Data Mining
» International Journal of Physical Medicine & Rehabilitation
»JBR Journal of Interdisciplinary Medicine and Dental Science
» Leukemia
» Liver
»Malaria Chemotherapy, Control & Elimination
» Medical & Surgical Urology
» Medical Diagnostic Methods
» Medical Microbiology & Diagnosis
» Metabolic Syndrome
» Molecular Biomarkers & Diagnosis
» Molecular and Genetic Medicine
» Mycobacterial Diseases
» Neonatal Biology
» Nephrology & Therapeutics
»Neuroinfectious Diseases
» Neurological Disorders
» Novel Physiotherapies
» Nuclear Medicine & Radiation Therapy
» Nursing & Care
» Nutritional Disorders & Therapy
» Obesity & Weight Loss Therapy
» Occupational Medicine & Health Affairs
» Oral Health and Dental Management
» Oral Hygiene & Health
» Orthopedic & Muscular System
» Osteoporosis & Physical Activity
» Otolaryngology
» Pain & Relief
» Palliative Care & Medicine
» Pancreatic Disorders & Therapy
» Pediatrics & Therapeutics
» Primary Health Care
» Psychological Abnormalities in Children
» Psychology & Psychotherapy
» Reproductive System & Sexual Disorders
»Research and Development
» Rheumatology: Current Research
» Sleep Disorders & Therapy
» Spine
» Sports Medicine & Doping Studies
» Steroids & Hormonal Science
» Surgery: Current Research
» Thyroid Disorders & Therapy
» Translational Medicine
» Trauma & Treatment
» Tropical Medicine and Surgery
» Vascular Medicine & surgery
» Women's Health Care
» Yoga & Physical Therapy
 
Management
» Accounting & Marketing
» Arabian Journal Business and Management Review
» Arts and Social Sciences Journal
» Business and Economics Journal
» Business and Financial Affairs
» Civil & Legal Sciences
» Defense Management
» Entrepreneurship & Organization Management
» Global Economics
» Hotel & Business Management
» Intellectual Property Rights: Open Access
»International Journal of Accounting Research
» International Journal of Economics & Management Sciences
» Mass Communication & Journalism
» political Sciences & public affairs
»Review of Public Adminstration and Management
» Socialomics
» Stock & Forex Trading
» Tourism & Hospitality
 
   Conferences
Upcoming Conferences
»3rd International Conference and Exhibition on Biosensors & Bioelectronics August 11-13, 2014 San Antonio, USA
»2nd World Associations Congress August 11-13, 2014 San Antonio, USA
»International Meeting on Space- Open Debate August 12-13, 2014 San Antonio, USA
»5th International Conference and Exhibition on Analytical & Bioanalytical Techniques August 18-20, 2014 Beijing, China
»2nd International Conference on Epidemiology and Evolutionary Genetics August 18-19, 2014 Beijing, China
»2nd International Conference and Exhibition on Pharmacognosy, Phytochemistry & Natural Products August 25-27, 2014 Beijing, China
»2nd International Conference and Exhibition on Traditional & Alternative Medicine August 25-26, 2014 Beijing, China
»2nd International Conference and Exhibition on Mechanical & Aerospace Engineering September 08-10, 2014 Philadelphia, USA
»2nd International Conference and Exhibition on Lasers, Optics & Photonics September 08-10, 2014 Philadelphia, USA
»3rd International Conference and Exhibition on Neurology & Therapeutics September 08-10, 2014 Philadelphia, USA
»4th International Conference on Pharmaceutical Regulatory Affairs September 08-10, 2014 Raleigh, USA
»2nd International Conference on Radiology and Imaging September 08-09, 2014 Raleigh, USA
»2nd International Conference on Genomics & PharmacogenomicsSeptember 08-09, 2014 Raleigh, USA
»2nd International Conference on Alzheimer's Disease and Dementia September 23-25, 2014 Valencia Convention Centre, Valencia, Spain
»3rd International Conference and Exhibition on Nutrition & Food Sciences September 23-25, 2014 Valencia, Spain
»3rd International Conference on Clinical Microbiology & Microbial Genomics September 24-26, 2014 Valencia, Spain
»3rd International Conference on Tissue Science & Regenerative Medicine September 24-26, 2014 Valencia, Spain
»4th International Conference on Vaccines & Vaccination September 24-26, 2014 Valencia, Spain
»3rd International Summit on GMP, GCP & Quality Control September 25-26, 2014 Valencia, Spain
»5th World Congress on Bioequivalence and Bioavailability: Pharmaceutical R&D Summit September 29-October 01, 2014 Baltimore, USA
»2nd International Conference on Hematology & Blood Disorders September 29-October 01, 2014 Baltimore, USA
»3rd International Conference and Exhibition on Clinical & Cellular Immunology September 29-October 01, 2014 Baltimore, USA
»3rd International Conference and Exhibition on Materials Science & Engineering October 06-08, 2014 San Antonio, USA
»3rd International Conference on Forensic Research and Technology October 06-08, 2014 San Antonio, USA
»4th World Congress on Virology October 06-08, 2014 San Antonio, USA
»2nd International Conference on Endocrinology October 20-22, 2014 Chicago, USA
»3rd 3rd International Summit on Toxicology & Applied Pharmacology October 20-22, 2014 Chicago, USA
»3rd 4th World Congress on Cancer Science and Therapy October 20-22, 2014 Chicago, USA
»3rd 3rd International Conference and Exhibition on Cell & Gene Therapy October 27-29, 2014 Las Vegas, USA
»2nd International Conference on HIV/AIDS, STDs & STIs October 27-29, 2014 Chicago, USA
»2nd World Congress on Petrochemistry and Chemical Engineering October 27-29, 2014 Las Vegas, USA
»3rd International Conference and Exhibition on Pharmacovigilance & Clinical Trials October 27-29, 2014 Hyderabad, India
»3rd International Conference and Exhibition on Biowaivers and Biosimilars October 27-29, 2014 Hyderabad, India
»3rd International Conference on Translational Medicine November 03-05, 2014 Las Vegas, USA
»2nd International Conference on Predictive, Preventive and Personalized Medicine & Molecular Diagnostics November 03-05, 2014 Las Vegas, USA
»5th International Conference on Diabetes & Metabolism November 03-05, 2014 Las Vegas, USA
»2nd International Congress on Bacteriology and Infectious Diseases November 17-19, 2014 Chicago, USA
»2nd International Conference on Nursing & Healthcare November 17-19, 2014 Chicago, USA
»3rd International Conference on Surgery and Anesthesia November 17-19, 2014 Chicago, USA
»4th International Conference on Nanotek & Expo December 01-03, 2014 San Francisco, USA
»3rd International Conference and Exhibition on Obesity & Weight Management December 01-03, 2014 San Francisco, USA
»2nd International Summit on Clinical PharmacyDecember 02-03, 2014 San Francisco, USA
»3rd International Conference on Medicinal Chemistry & Computer Aided Drug Designing December 08-10, 2014 San Francisco, USA
»3rd International Conference and Exhibition on Probiotics & Functional Foods December 08-10, 2014 San Francisco, USA
Previous Conferences Organized/Co-organized
»Health Informatics & Technology Conference July 28-29, 2014 Baltimore, USA
»3rd International Conference on Gastroenterology & Urology July 28-30, 2014 San Francisco, USA
»3rd International Conference on Earth Science & Climate Change July 28-30, 2014 San Francisco, USA
»3rd International Conference and Exhibition on Orthopedics & Rheumatology July 28-30, 2014 San Francisco, USA
»International Conference on Business Economics of Broadcasting Media & Film Industry July 28-30, 2014, Baltimore, USA
»4th International Conference on Proteomics & Bioinformatics August 04-06, 2014 Chicago, USA
»3rd International Conference and Exhibition on Addiction Research & Therapy August 04-06, 2014 Chicago, USA
»2nd International Conference on Integrative Biology Summit August 04-05, 2014 Chicago, USA
»3rd International Conference and Exhibition on Cosmetology & Trichology July 21-23, 2014 Las Vegas, USA
»3rd International Conference and Exhibition on Food Processing & Technology July 21-23, 2014 Las Vegas, USA
»2nd International Conference on Oceanography July 21-23 , 2014 Las Vegas USA
»4th International Conference on Clinical & Experimental Ophthalmology July 14-16, 2014 Baltimore, USA
»3rd International Conference & Exhibition on Biometrics & Biostatistics July 14-16, 2014 Baltimore, USA
»2nd International Conference and Exhibition on Physical Medicine & Rehabilitation July 14-16, 2014 Baltimore, USA
»International Conference on Geriatrics & Gerentology July 08-10, 2014 Chicago , USA
»International Conference on Women's Health, Gynecology & Obstetrics July 08-10, 2014 Chicago, USA
»International Conference on Computer Graphics and Media Design July 08-10, 2014 Chicago, USA
»4th International Conference on Clinical & Experimental Cardiology April 14-16, 2014 San Antonio, USA
»4th International Conference on Clinical & Experimental Dermatology April 14-16, 2014 San Antonio, USA
»3rd International Conference and Exhibition on Pathology April 14-16, 2014 San Antonio, USA
»5th International Conference on Biomarkers and Clinical Research April 15-17, 2014 University of Oxford, UK
»2nd International Conference on Business Economics and Management April 21-23, 2014 Dubai, UAE
»2nd International Conference on Dental and Oral Health April 21-23, 2014 Dubai, UAE
»4th World Congress on Cell Science & Stem Cell Research June 24-26, 2014 Valencia, Spain
»3rd International Conference on Biodiversity & Sustainable Energy Development June 24-26, 2014 Valencia, Spain
»3rd International Conference and Exhibition on Occupational Health & Safety June 24-25, 2014 Valencia, Spain
»5th World congress on Biotechnology June 25-27, 2014 Valencia, Spain
»3rd International Conference on Nephrology & Therapeutics June 26-27, 2014 Valencia, Spain
»2nd International Conference on Bioprocess and Engineering June 26-27, 2014 Valencia, Spain
»2nd International Conference on Dental and Oral Health April 21-23, 2014 Dubai, UAE
»5th International Conference on Biomarkers and Clinical Research April 15-17, 2014 University of Oxford, UK
»3rd International Conference and Exhibition on Pathology April 14-16, 2014 San Antonio, USA
»4th International Conference on Clinical & Experimental Dermatology April 14-16, 2014 San Antonio, USA
»4th International Conference on Clinical & Experimental Cardiology April 14-16, 2014 San Antonio, USA
»4th International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems March 24-26, 2014 San Antonio, USA
»3rd International Conference and Exhibition on Metabolomics & Systems Biology March 24-26, 2014 San Antonio, USA
»2nd International Conference on Agricultural & Horticultural Sciences, February 03-05, 2014 Hyderabad, India
»International Conference and Exhibition on Traditional & Alternative Medicine, December 09-11, 2013 Hyderabad, India
»2nd International Conference and Exhibition on Obesity & Weight Management, December 02-04, 2013 Las Vegas, USA
»International Conference on Nursing & Emergency Medicine, December 02-04, 2013 Las Vegas, USA
»3rd International Conference on Nanotek & Expo, December 02-04, 2013 Las Vegas, USA
»3rd World Congress on Virology, November, 20-22, 2013 Baltimore, USA
»International Congress on Bacteriology and Infectious diseases, November 20-22, 2013 Baltimore, USA
»3rd World Congress on Cell Science & Stem Cell Research, November 20-22, 2013 San Antonio, USA
»2nd International Conference and Exhibition on Pharmacovigilance & Clinical Trials, November 18-19, 2013 San Antonio, USA
»International Summit on Clinical Pharmacy & Dispensing, November 18-20, 2013 San Antonio, USA
»World Congress on Petrochemistry and Chemical Engineering, November 18-20, 2013 San Antonio, USA
»International Conference on Functional and Comparative Genomics & Pharmacogenomics, November 12-14, 2013 Chicago, USA
»2nd International Conference and Exhibition on Cosmetology & Trichology, November 12-14, 2013 Chicago, USA
»2nd International Summit on GMP, QA & QC, November 12-14, 2013 Chicago, USA
» International Conference on Fermentation Technology, Bioprocess and Cell Culture, October 28-30, 2013 Kansas City, USA
»2nd International Conference and Exhibition on Food Processing & Technology, October 28-30, 2013 Kansas City, USA
»International Conference on HIV/AIDS, STDs, & STIs, October 24-25, 2013 Orlando-FL, USA
»2nd International Conference and Exhibition on Cell & Gene Therapy, October 23-25, 2013 Orlando, USA
»2nd International Conference and Exhibition on Probiotics & Functional Foods, October 23-25, 2013 Orlando, USA
»International Conference and Exhibition on Pharmacognosy, Phytochemistry and Natural Products, October 21-23, 2013 Hyderabad, India
» 3rd World Congress on Cancer Science & Therapy, October 21-23, 2013 California, USA
»3rd International Conference on Pharmaceutical Regulatory Affairs, October 21-23, 2013 California, USA
»2nd International Conference on Clinical & Cellular Immunology, October 15-17, 2013 Las Vegas, USA
»2nd International Conference on Medicinal Chemistry & Computer Aided Drug Designing, October 15-17, 2013 Las Vegas, USA
»4th International Conference and Exhibition on Analytical & Bioanalytical Techniques, October 15-17, 2013 Las Vegas, USA
»2nd International Summit on Toxicology, October 07-09, 2013 Las Vegas, USA
»International Conference and Exhibition on Lasers, Optics & Photonics, October 7-9, 2013 San Antonio, USA
»2nd International Conference and Exhibition on Materials Science & Engineering, October 07-09, 2013 Las Vegas, USA
»International Conference and Exhibition on Biochemical & Molecular Engineering, October 07-08, 2013 San Antonio, USA
»International Conference on Psychology, Autism and Alzheimer's Disease, September 30-October 01, 2013 San Antonio, USA
»International Conference and Exhibition on Mechanical & Aerospace Engineering, September 30-October 02, 2013 San Antonio, USA
»2nd International Conference and Exhibition on Biowaivers & Biosimilars, September 23-25, 2013 Raleigh, USA
»4th World Congress on Biotechnology, September 23-25, 2013 Raliegh, USA
»International Conference on Hematology & Blood Disorders, September 23-25, 2013 Raliegh, USA
»2nd International Conference on Surgery and Anesthesia, September 16-18, 2013 Las Vegas, USA
»2nd International Conference on Clinical Microbiology & Microbial Genomics, September 16-18, 2013 Las Vegas, USA
» International Conference on Omics Studies, September 04-06, 2013 Orlando-FL, USA
»International Symposia on Entomology, September 04-06, 2013 Miami, USA
» World Congress on Endocrinology, August 26-28, 2013 Raleigh, USA
»2nd International Conference on Hydrology and Groundwater Expo, August 26-27, 2013 Raleigh, USA
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Review Article Open Access
 
The Role of Biological Agents in Immunotherapy
Department of Trauma and Orthopaedic Surgery, Leeds General Infirmary, Great George Street, Leeds, UK Imran Haruna Abdulkareem*
 
Corresponding Author : Imran Haruna Abdulkareem
Department of Trauma and Orthopaedic Surgery
Registrars’ office, B Floor Clarendon Wing
Leeds General Infirmary
Great George Street, Leeds, UK
E-mail: imranharuna@yahoo.com
 
Received April 20, 2013; Accepted May 18, 2013; Published May 25, 2013
 
Citation: Abdulkareem IH (2013) The Role of Biological Agents in Immunotherapy. Metabolomics 3:116. doi: 10.4172/2153-0769.1000116
 
Copyright: © 2013 Abdulkareem IH. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
 
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Abstract
 

Many autoimmune diseases and cancers have an underlying immune basis, and these include Systemic Lupus Erythematosus (SLE), rheumatoid arthritis, systemic sclerosis, ankylosing spondylitis, as well as breast cancer. Biological therapies are monoclonal antibodies and fusion proteins which contain specific recognition components that have antibody function. This principle takes advantage of antigen specificity to produce monoclonal antibodies to the desired antigen. Problems of biological therapies include ethical, regulatory, and licensing issues, documentation of trials, funding, adverse effects, media attention and publicity, selection issues, time considerations and risk-benefit analysis. Therefore, proper and strict regulation of research on humans as well as use of these biological agents should be carefully enforced and monitored by the authorities, to ensure maintenance of transparency and good standards.

 
Keywords
 
Biological agents; Immunotherapy; Monoclonal antibodies; Autoimmune diseases; Cancers; Adverse effects; Regulations
 
Introduction
 
Many diseases have been observed to have an underlying immune basis and include auto-immune diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis and systemic sclerosis [1]. Auto-reactive T cells are kept under control by the regulatory T cells (Treg cells) and absence of co-stimulatory signalling leads to loss of Treg cells [2]. CD28 super-agonists have been observed to cause selective expansion and activation of the regulatory T cells over conventional T cells (Tconv cells) and so it was thought that this anti-CD28 antibody represented a promising new treatment option for the large number of human auto-immune diseases [3].
 
The co-stimulatory signal
 
Bretscher and Cohn in 1970 proposed the two signal model of lymphocyte activation to enable understanding of self/non-self discrimination, and this model suggested that T cell activation needs two separate signals. The first is transmitted through the T cell receptor (TCR) following binding of antigen, and the second co-stimulatory signal occurs through the binding of a separate receptor (CD28) on the T cell [4]. It has been observed that antigenic stimulation of the T cells without this co-stimulatory signal will result in a state of unresponsiveness called anergy and the anergic T cells fail to produce interleukin 2 (IL-2) and other cytokines required for T cell function and regulation [5]. CD28 is important for regulating immune responses and maintaining peripheral tolerance. Binding of this receptor to its ligands causes increased expression of CTLA-4 (Cytotoxic T lymphocyte antigen-4), which has a negative effect on T cell activation. This binding facilitates the differentiation of Th2 cells which have protective functions in auto-immunity, as well as control of the regulatory T cells [6].
 
What is CD28?
 
First cloned by Arrufo and Seed in 1987, and initially called TP44, this is a protein that belongs to the IgSF (immunoglobulin superfamily) group of receptors with a molecular weight of 44 KDa. It is expressed by sub-populations of T cells and activated B lymphocytes [7], as well as neutrophils and [3]. It is expressed before activation of T cells takes place.The ligands for this receptor are CD80/CD86 (B7.1 and B7.2) co-stimulators which are generally found on antigen presenting cells (APCs), and also bind to the counter-stimulatory receptor CTLA- 4 that is expressed after T cell activation to produce a negative effect. CTLA-4 has higher affinity for the ligands (B7.1 and B7.2) than CD28 and leads to blockade of further activation signal [5]. B7.2 (CD86) is the predominant co-stimulatory ligand for CD28 [4].
 
Consequences of CD28-B7 Interaction
 
CD28 stimulation causes transcriptional activation and posttranslational stabilisation of mRNA leading to increased expression of cytokines such as interleukin 2 (IL-2) and activation of protein kinase AKT [4]. It also prevents anergy and causes induction of the anti-apoptotic factor BCL-XL, contributes to B cell differentiation, antibody production, direction of T cell migration and the regulation of chemokine receptors [6].
 
The Role of regulatory T cells
 
These are CD4+ CD25+ cells with regulatory function and known as Tregs. They make up to about 5-15% of the peripheral CD4+ T cells. They constitutively express the interleukin 2 receptor-α chain (CD25) and CTLA-4. The development and survival of these cells in the thymus is controlled by CD28, which maintains their function independent of CTLA-4. This is important in the maintenance of tolerance, prevention of auto-immunity, enhancement of T cell response to pathogens, and prevention of transplant rejection [6]. In addition to that, the CD28- mediated up-regulation of the inhibitory molecule CTLA-4 prevents potentially harmful inflammation by terminating normal immune responses [4].
 
Molecular properties of CD28 “super-agonist”
 
The super-agonist anti-CD28 antibody has been observed to bind to a lateral membrane –proximal loop of the molecule (C”D loop) and interaction of the antibody with the extracellular domain of human CD28 leads to a linear complex formation. The conventional anti- CD28 antibodies bind CD28 bivalently, but result in the formation of tangled complexes. Complex formation of the CD28 causes aggregation of stimulatory signalling components such as PI3 kinase and growth factor receptor bound protein (Grb 2) leading to generation of strong activating signal.
 
Rationale for using anti-CD28 antibody
 
Monoclonal antibodies and fusion proteins with specificity for the T cell receptor (TCR) and CD28 have been found promising in the treatment of auto-immune diseases [1]. Both the anti-TCR monoclonal antibodies and the “conventional” anti-CD-28 monoclonal antibodies individually are unable to stimulate the T cells and need to be combined to produce T cell activation and cytokine production. But the CD28 “super-agonists” are able to cause T cell activation without the need for TCR stimulation, hence the name super-agonists. This is why it was thought by many workers that these monoclonal antibodies will have a place in the treatment of auto-immune diseases which are refractory to the conventional treatments available to patients [3].
 
It has been observed that CD28 super-agonist administration in vivo causes selective expansion and strong activation of the naturallyoccurring CD4+CD25+CTLA-4+FOXP3+ Treg cells over conventional T cells (Tconv cells), and absence of this signalling leads to loss of these regulatory cells. Also, a functional and/or numerical deficit in Treg cells compared to pathogenic auto-reactive cells leads to initiation of autoimmunity. Therefore, it is believed that because Treg cells are the main controllers of peripheral self tolerance, this new therapy which aims at re-establishing the balance between auto-reactive T cells and Treg cells could have important contributions in the treatment of auto-immune diseases [2].
 
Furthermore, application of CD28 super-agonists was noted to result in momentary increase in the percentage of Treg cells which was dose-dependent. This preferential expansion of Treg cells over Tconv is thought to result from generation of extremely strong or sustained signal in Treg cells following super-agonistic anti-CD28 stimulation. This is in addition to the production of BCL-XL which is an anti-apoptotic factor that prevents cell death. Also, increased interleukin synthesis by Tconv cells and its uptake by the Treg cells are thought to contribute to the preferential expansion of the latter cells following super-agonistic CD28 stimulation [4]. Beyersdorf et al. [2] also suggested that Treg cells may have selective advantage over Tconv cells because of active suppression of the latter during super-agonistic CD28 stimulation by activating the cell contact-dependent suppressor machinery which only functions upon recognition of self antigens in vivo.
 
Lastly, it has been observed that administration of CD28 super-agonist to animals with EAE (experimental auto-immune encephalomyelitis) and experimental auto-immune neuritis (EAN) which resemble multiple sclerosis and Gullain-Barre syndrome respectively, prevented or reduced the clinical symptoms when given before the onset of the disease. This monoclonal antibody also rapidly stopped the disease progression and produced disease remission even after the onset of symptoms [2]. This evidence was supported by adoptive transfer experiments which revealed that transfer of CD28 super-agonist-activated Treg cells protected recipient animals from the clinical signs of EAE, and CD4+ CD25- T cells (Tconv) cells were observed to lack any protective effect in spite of ten times greater dose of administration [8].
 
Because both the pharmaco-dynamics and toxicological profiles of the CD28 super-agonist suggested that it was safe, it was thought to have clinical relevance in patients with multiple sclerosis and rheumatoid arthritis who are known to have deficits in Treg cell numbers and/or function with the aim of curing them. The hope was that these patients might benefit from a boost in their Treg cells following the super-agonist administration to improve their clinical symptoms [1,2].
 
What are biological therapies?
 
These are monoclonal antibodies and fusion proteins which contain specific recognition components that have antibody function. The principle of biological therapy takes advantage of antigen specificity to produce monoclonal antibodies to the desired antigens [1]. Currently used biological therapies in clinical practice include Adalimumab, Etanercept, Infliximab, Rituximab, Ibritumomab tiuxetan, Tositumomab and Iodinated Tositumomab (I-131), Basiliximab, Daclizumab, Alemtuzumab, Cetuximab, Bevacizumab, Trastuzumab, and Palivizumab [1].
 
Sources of biological therapies
 
Kohler and Milstein first developed hybridoma technology in early 1970s, and set the pace for the development of monoclonal antibody therapeutics. This was followed later on by the development of hybridomas by the fusion of B cells from immunised mice with murine myeloma cell lines. The immortalised cell lines (clones) were then selected according to the antibody of interest which is then produced in large quantities. This came with problems because it was difficult to produce human anti-mouse antibodies that can be used without immunogenic complications [5].
 
Genetic manipulations allowed the development of chimeric antibodies which are obtained from a combination of murine variable-region genetic material with human constant-region genes. A combination of murine CDR genetic material with the remaining part of the antibody obtained from humans results in humanised antibodies. Lastly, fully human monoclonal antibodies have their origin completely from human beings [1]. Humanised antibodies are superior because they have better interaction with human Fc receptors and effector cells, which gives a greater effector function and less immunogenic reaction. This prolongs the therapeutic half-life of the drug and reduces the side effects especially following subsequent exposures [1].
 
The function of the monoclonal antibody can be determined by selecting a particular Fc component. This can be coupled with a specific molecule to form a fusion protein that has both the antibody effector function and any other desired effects. Finally, monoclonal antibodies can be changed and used for immunotherapy by labelling them with toxins specific for cancer cells without affecting the normal cells [7].
 
Problems of biological therapies
 
Biological therapies are associated with a lot of problems which include regulatory/licensing issues, documentation of the trials (recording and reporting), funding, side effects and complications (short- and long-term), ethical considerations, media attention and publicity, selection of the immune component to be modified, time considerations, risk-benefit analysis and when to use the therapy [1]. I shall therefore attempt to briefly highlight each of the issues involved.
 
Regulatory and Licensing Issues
 
Biological therapies are potentially harmful agents and so there is need for involvement of licensing and regulatory agencies like the UK Medicines and Healthcare Products Regulatory Agency (MHRA), and independent research ethics board (REB) right at the beginning of conception of the idea through to the pre-clinical and clinical studies [9]. This will help to create checks and balances and highlight any potential hazardous effects of the agent before it is tried on humans. This protocol has been observed in the case of TGN1412 because three independent bodies reviewed the drug before it was tried in the six volunteers. It is also important for drug investigators and sponsors to provide accurate, complete and unbiased information to the regulatory bodies and ensure transparency throughout the development of new drugs, in addition to the need for compulsory registration and disclosure of the trials and protocols to the regulatory agencies and public [10].
 
Problems of Funding
 
It is important to note that the process of drug development is very expensive and capital intensive [1], hence the need for research grants and financial support from governments, international agencies and pharmaceutical companies, which will help to convert the idea into a finished product ready for use. In addition to that, even the trials (both pre-clinical and clinical) are capital intensive and add to the cost of drug manufacturing. Lastly, use of the drug is also expensive because it has to be procured by the governments or sometimes the individuals have to pay for the drug according to its availability, this may be worsened by the added treatment of side effects and complications. In addition to all that, the cost of not treating the patient also needs to be considered as it may be more expensive than treating the patient with the therapy in question.
 
Side Effects of the Drugs
 
Safety issues in drug trials are of utmost importance, because of the possible side effects which can be short- or long-term. Any system can be affected depending on the type of monoclonal antibody used and its intended target(s). Immunosuppression can lead to fungal and opportunistic infections, involvement of the gastro-intestinal system may lead to nausea, vomiting, and diarrhoea, while affectation of the respiratory system will lead to difficulty in breathing, chest pain and even respiratory as well as cardiovascular failure. In addition to that shock and hypovolaemia may result in acute renal failure which may present in decreased or complete lack of urine formation [1].
 
Occasionally, multiple organ failure can occur with affectation of virtually all the systems at once as can be seen in the case of trial with TGN1412 [10]. Within 90 minutes of receiving this monoclonal antibody, all the six volunteers developed a systemic inflammatory response syndrome as evidenced by headache, myalgias, nausea, diarrhoea, erythema, vasodilatation and hypotension. There was also recurrent fever, respiratory difficulty, cardiovascular shock, renal failure, hospital-acquired infections, peripheral ischaemia, disseminated intravascular coagulation and generalised skin desquamation [11].
 
Long-term side effects and complications are also to be expected in some cases and these can include chronic low blood cell count, anaemia, cancers, autoimmune diseases, decreased life expectancy and resurgence of infections like tuberculosis in patients that received anti-TNFα therapy [1]. This is because TNF-α is required for the formation of localised tuberculous granuloma, which helps to localise the infection in one place and so may remain dormant for a long time.
 
Ethical Considerations
 
These are very important issues to be considered so as to be sure the subject/patient is given his/her right to know and make judgements before any clinical trials can be done on them. This can be complicated by the need to reward or pay the subjects for their participation which many believe can cloud or bias their judgements in taking a reasonable decision to partake in a drug trial [10]. But Emanuel and Miller [9] caution that although the role of money cannot be over-emphasised, bad things can happen in ethical research, but money does not make them unethical, unscrupulous or malignant. They further noted that a research is ethical from the beginning, good outcomes do not necessarily make it ethical, and a bad outcome does not make an ethical research unethical. Among the many ethical issues to be considered include the need to conduct research in a particular disease area and whether it is justified. Others are the need for scientific validity which require that pre-clinical studies are conducted using cell cultures and laboratory animals before clinical trials are carried out, fair subject selection should be done without targeting vulnerable and marginalised communities, taking informed consent and respecting the enrolled participants as well as granting them the right to withdraw from any trials at any time [1,9].
 
Risk-benefit analysis
 
It is important to make a careful assessment in order to weigh the risks of any drug use against the benefits so as to avoid mistakes and end up with litigation. In the case of the TGN1412 phase 1 clinical trial, healthy male adult volunteers were used even though the drug was meant for patients with compromised immune systems, and therefore some felt that real patients who stood to benefit from the drug should have been co-opted into the trial [10]. But Emanuel and Miller [9] suggested that even though the volunteers had no chance of benefiting directly from the trials (medically), the medical knowledge to be gained could be used to justify the risk of the trials.
 
Media Publicity
 
Although it is important for drug developers to be open and transparent during drug research, negative media attention and bad publicity need to be discouraged, in order to prevent fear and panic in the public which can lead to refusal or rejection of new therapies. It is important for health personnel to educate themselves and their patients on the benefits and/or hazards of new therapies and how they work. This will ensure patient’s trust and compliance with medication, an important consideration in their treatment to ensure good outcomes [9].
 
Conclusion
 
Anti-CD28 monoclonal super-agonist and other biological agents have definite roles in the treatment of auto-immune diseases and even cancers, because of their ability to enhance regulatory T cell function, but there is need to carry out careful and meticulous pre-clinical trials before trying them on humans under close observation, given to one person at a time to prevent disastrous outcomes. Proper and strict regulation of research on humans, as well as use of these biological agents should be enforced and monitored by the authorities to ensure maintenance of transparency and good standards.
 
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