Overview of vaccine and vaccination, types of vaccines with examples, vaccine production technique, adverse effects of vaccination, precautions
Email: jeevan@smail.nchu.edu.tw
vaccine is a biological preparation that provides active acquired immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and to further recognize and destroy any of the microorganisms associated with that agent that it may encounter in the future.
HISTORY OF VACCINES-
EDWARD JENNER conduct experiments in 1796 that lead to the creation of the first smallpox vaccine for prevention of smallpox.
A vaccine for RABIES is developed by LOUIS PASTEUR .
Vaccine for COLERA and TYPHOID were developed in 1896 and PLAGE vaccine in 1887.
The first DIPHTHERIA vaccine is developed in about 1913 by EMIL ADOLPH BEHRING,WILLIAM HALLOCK PARK.
The whole cell PERTUSIS vaccines are developed in 1914.
A TETANUS vaccine is developed in 1927.
Types of Vaccines with live attenuated, inactivated up to recombination technique. OPV and IPV difference and rationale to replace OPV with IPV. EPI schedule of nepal
Overview of vaccine and vaccination, types of vaccines with examples, vaccine production technique, adverse effects of vaccination, precautions
Email: jeevan@smail.nchu.edu.tw
vaccine is a biological preparation that provides active acquired immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and to further recognize and destroy any of the microorganisms associated with that agent that it may encounter in the future.
HISTORY OF VACCINES-
EDWARD JENNER conduct experiments in 1796 that lead to the creation of the first smallpox vaccine for prevention of smallpox.
A vaccine for RABIES is developed by LOUIS PASTEUR .
Vaccine for COLERA and TYPHOID were developed in 1896 and PLAGE vaccine in 1887.
The first DIPHTHERIA vaccine is developed in about 1913 by EMIL ADOLPH BEHRING,WILLIAM HALLOCK PARK.
The whole cell PERTUSIS vaccines are developed in 1914.
A TETANUS vaccine is developed in 1927.
Types of Vaccines with live attenuated, inactivated up to recombination technique. OPV and IPV difference and rationale to replace OPV with IPV. EPI schedule of nepal
A vaccine is a biological preparation of weakened or killed pathogen such as bacterium or virus that will improves immunity to a particular diseases.
The principle of immunization or vaccination is based on the property of ‘memory’ of the immune system.
The process of introduction of vaccine into an individual to provide protection against a disease called vaccination.
SYNTHETIC PEPTIDE VACCINES AND RECOMBINANT ANTIGEN VACCINED.R. Chandravanshi
What is a Vaccine?
A vaccine is a substance that is introduced into the body to prevent infection or to control disease due to a certain pathogen (a disease-causing organism, such as a virus, bacteria or parasite). The vaccine “teaches” the body how to defend itself against the pathogen by creating an immune response.
1 Unlike traditional pharmaceuticals, vaccines are biologics since they are made from living organisms (biological sources).
2 Specifically, vaccines are preparations of components derived from (or related to) a pathogen; they can typically induce a protective effect through one to three very small doses, in the range of micrograms to milligrams.
3 Immunity lasts for an extended period, from one year up to lifetime protection, including prevention of disease and/or related sequelae.
Synthetic peptide vaccines represent fragments of protein antigen sequences, synthesizing specific B cell and T cell epitopes offer the potential to induce diseases neutralizing immuno response with completely synthetic structure. Now it is well established that short chain peptides can be used to mimic antigenic sites of viruses and thus can be used the basics for vaccines and development. therefore, attempts have been made to synthesize such peptides which act as the serrogate immuunogens, as an alternative to the existing conventional vaccines.
Introduction
Definition
History
Why are the transgenic animals being produced
Transgenic mice
Mice: as model organism
Methods of creation of transgenic mice
knock-out mice
Application of transgenic mice
Conclusion
References
A vaccine is a biological preparation of weakened or killed pathogen such as bacterium or virus that will improves immunity to a particular diseases.
The principle of immunization or vaccination is based on the property of ‘memory’ of the immune system.
The process of introduction of vaccine into an individual to provide protection against a disease called vaccination.
SYNTHETIC PEPTIDE VACCINES AND RECOMBINANT ANTIGEN VACCINED.R. Chandravanshi
What is a Vaccine?
A vaccine is a substance that is introduced into the body to prevent infection or to control disease due to a certain pathogen (a disease-causing organism, such as a virus, bacteria or parasite). The vaccine “teaches” the body how to defend itself against the pathogen by creating an immune response.
1 Unlike traditional pharmaceuticals, vaccines are biologics since they are made from living organisms (biological sources).
2 Specifically, vaccines are preparations of components derived from (or related to) a pathogen; they can typically induce a protective effect through one to three very small doses, in the range of micrograms to milligrams.
3 Immunity lasts for an extended period, from one year up to lifetime protection, including prevention of disease and/or related sequelae.
Synthetic peptide vaccines represent fragments of protein antigen sequences, synthesizing specific B cell and T cell epitopes offer the potential to induce diseases neutralizing immuno response with completely synthetic structure. Now it is well established that short chain peptides can be used to mimic antigenic sites of viruses and thus can be used the basics for vaccines and development. therefore, attempts have been made to synthesize such peptides which act as the serrogate immuunogens, as an alternative to the existing conventional vaccines.
Introduction
Definition
History
Why are the transgenic animals being produced
Transgenic mice
Mice: as model organism
Methods of creation of transgenic mice
knock-out mice
Application of transgenic mice
Conclusion
References
a research presentation done by Augustine Mwaawaaru Level 400) and Matthew Frimpong Antwi (Level 300) students of( Presbyterian University College-Ghana on Antimicrobial resistance and the way foeward in Ghana. contact 0261825262
development of antimicrobial agents which can overcome the antimicrobial resi...Arijit Goswami
as the microorganisms are increasingly becoming resistant to conventional antibiotics therefore there is a need of some new antimicrobial gents which can overcome the resistance and also helps to stop the overuse and mishandling of antibiotics
Endocrine Disruptors presentation will inform our readers about different disruptors that affect the everyday lives of people: BPA, MethylMercury, Pesticides, Phthalates, and Soy all these will inform the reader about the hazards, exposure, and the alternatives behind these disruptors.
Immunomodulators modern and ayuvedic conceptsJAYAKRISHNAN K
A MINOR SIMPLE PROJECT ON IMMUNOMODULATORS. It explains types of immunity, hyper sensitivity, allergy, immunostimulants, immunoadjuvants, immunosuppressants etc. with relevant ayurvedic portions.
Increasing Trends in Male Reproductive Disorders, Environmental Exposures, an...DES Daughter
On this call, Dr. Skakkebaek presented his concerns about increasing trends in male reproductive disorders, including the significant global increase in incidence of germ cell tumors. He and colleagues from all over the world demonstrated that over half of all young men's semen quality does not meet the reference standard of the World Health Organization. Dr. Skakkebaek presented evidence linking testicular cancer, poor semen quality, childlessness, and rapidly decreasing fertility rates. He showed how there is little doubt that environmental factors, most likely associated with modern lifestyles, have - in a broad sense - had an adverse influence on male reproductive health. He and his group are examining a fundamental role that exposure to endocrine-disrupting chemicals may play in these trends, trends that in a few decades will result in decreasing populations in industrialized countries, and believes collaborative research is required to identify the causes of these adverse trends.
Sources: http://healthandenvironment.org/partnership_calls/18355
Endocrine disruptors in the healthcare sectorDES Daughter
Created for healthcare professionals on EDCs, this slideshow by Health Care without Harm Europe (HCWH) examines the reasons why we should be concerned, who is at risk, including on pregnant women and babies, and where EDCs are hidden in the healthcare sector.
Sources: https://noharm-europe.org/documents/presentation-slides-webinar-edcs-healthcare
Leaflet: https://noharm-europe.org/documents/edc-leaflet-health-professionals
INTRODUCTION OF VACCINE & VACCINATION.
HISTORY.
TYPRE OF VACCINE
CONTRAINDICATION.
CLASSIFICATION ACCORDING TO PATHOGEN.
PRECAUTION BEFORE TO VACCINE.
DRUGS ADMINISTRATION -: ROUTES & DOSE
SUMMARY.
REFERENCES.
ASSESSMENT QUESTIONS
This is an immunology lecture for medical students. it helps student to understand the importance of immunization in clinical practice. resident doctors can also benefit immensely with this lecture.
vaccine train user immune system to create antibodies, just as it when it is exposed to a disease. However, because vaccine contain only killed or weakened forms of germs like viruses or bacteria, they do not cause the disease or put you at the risk of complications.
vaccine is a biological preparation that improve immunity to a particular disease.
A vaccine typically contain an agent that resembles a disease causing microorganisms and is often made from weakened or killed forms of the microbes.
Immunity: Protection from an infectious disease. If you are immune to a disease, you can be exposed to it without becoming infected.
Vaccine: A preparation that is used to stimulate the body’s immune response against diseases. Vaccines are usually administered through needle injections, but some can be administered by mouth or sprayed into the nose.
Vaccination: The act of introducing a vaccine into the body to produce protection from a specific disease.
Biochemistry of Hair fall, A complete review of hair fall cause, Types, Current methods of treatment, Natural methods of treatment,
for more detail text see :https://iiopinion.blogspot.in/2017/01/hair-fall-scientific-way-of-treatment.html
Non-Specific Immune Response, Innate immunity, inherent immunity, Role in overall immunity of individual, Significance, components involve in Non-Specific Immune Response,
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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2. Objectives
The role of immunological memory in protection against infectious diseases
The main differences between memory and naïve T and B cells
How vaccines can be used to manipulate the immune response to induce
immunological memory
Examples of attenuated vaccines are and how they are produced.
Examples of killed vaccines are and how they are produced.
Examples of recombinant vaccines are and how they are produced
Current experimental approaches to design vaccines and their associated
problems :
Recombinant plant vaccines
Live recombinant vaccines
Genetically attenuated vaccines
Peptide vaccines
DNA vaccines
3. What vaccine adjuvants are and their
functions in vaccine formulations
Which adjuvants are used in human
vaccines
The types of responses induced by
adjuvants
The current status of research into HIV,
Malaria and TB
4. Definition
Vaccines are a manipulation of the
adaptive immune response whereby the
host is induced to generate a protective
immune response to a pathogenic
organism without actually experiencing
the full infection.
Vaccination involves deliberate
exposure to antigen under conditions
where disease should not result.
5. Role of Memory in Vaccine induced
protection to infection
During this primary challenge, the immune response responds by
producing not only effector cells but also memory cells Compared
with naïve T cells, memory T cells: Are Long Lived
Have Increased frequency
Proliferate more rapidly
Have reduced co-stimulatory requirements (signal 2)
Compared with naïve B cells, memory B cells : Are Long Lived
Have Increased frequency
Proliferate more rapidly
Produce more Ab
Produce higher affinity Ab
Produce antibodies with better effector functions (IgG & IgA)
6. secondary antibody response to antigen.
Memory T and B cells induced during vaccination facilitate
more rapid control of subsequent infections with pathogens.
This can be seen most clearly in the secondary antibody
response to antigen. Secondary antibody responses are T cell
dependent. During the primary response, expansion of T
cells specific for protein antigens is sufficient for the host to
mount a secondary antibody response on subsequent
exposure to that antigen, plus any other B cell antigen which
is physically associated with it (e.g. a hapten). This is known
as the carrier effect - it means that the secondary antibody
response to a vaccine can be induced by conjugating the B
cell antigen of choice to a T cell antigen to which people have
already been exposed (see the Hib vaccine below)
7. History of Vaccination
Jenner performed the definitive experiments to demonstrate
effective protection against smallpox (causative agent,
Variola) by prior inoculation or ‘vaccination’ with cowpox
(containing the closely related Vaccinia virus) in 1796. The
‘golden age of microbiology’ brought about the rapid
isolation of the pathogenic agents of many diseases and
subsequent attempts to produce vaccines against them. In
the 1880’s Pasteur generated attenuated versions of polio
virus and anthrax by in vitro culture. Subsequent methods of
producing vaccines included heat or chemical inactivation of
pathogens. After improvements in living conditions, vaccines
are the most effective public health measure introduced. In
Glasgow in the 1900’s, 1 in 5 deaths were due to smallpox
infection. In May 1980, the WHO officially announced the
global eradication of the smallpox virus.
8. Currentstatus
ThefollowingvaccinesarerecommendedforroutinevaccinationintheUK
• Diphtheria/
Tetanus/Pertussis
(DTP)
1st @ 2 months
2nd @ 3 months
3rd @ 4 months
• DT boost and
Polio boost
13-18 years
• Haemophilus
influenzae B (Hib)
schedule as
above
• Hepatitis A high risk groups
• Polio schedule as
above
• Hepatitis B high risk groups
• Measles/
Mumps/Rubella
12 - 15 months • Influenza high risk groups
• DT boost, MMR
boost, and Polio
3-5 years • Pneumococcal
vaccines
high risk groups
• BCG 10-14 years
9. Producing Vaccines
The whole point of vaccination is to induce a
protective immune response as would be elicited
by infection, with minimal disease associated
with the infection. This can be achieved by
producing attenuated strains of bacteria or
viruses, for example: host range mutants
where bacteria or viruses (e.g. BCG or Sabin
polio virus) are selected for in vitro growth in
non-human cells
cold attenuated mutants where viruses are
grown at temperatures of 32-34ûC, well below
body temperature e.g. Measles.
10. Procedures to produce undefined mutations
the bacteria or virus
allow it to grow
well under all
possible condition
in vitro specific
conditions.
After a great deal of selection for safety and stability, the mutated,
attenuated virus or bacteria will not grow as well in humans as the
wild type organism and can be used as a vaccine.
Over many years the
BCG vaccine has
been selected for
reduced local
reactions at the site
of injection.
This has raised concerns that due to
selection, the vaccine is now of limited
effectiveness in conferring protection against
TB
11. Other techniques for vaccine production are:
• Usually using chemicals such as formaldehyde
Killed
vaccines
• Toxins are the pathogenic fragments of bacteria
• Antibodies to toxins can protect against infection and disease
• Chemically inactivated toxins are called toxoids
Subunit
Vaccines
• Polysaccharides are T cell independent (no memory)
• Hib vaccine is conjugated to tetanus or diphtheria toxoid
Conjugate
vaccines
• Hepatitis B is the only recombinant vaccine
• HBsAg expressed in yeast
Recombinant
vaccines
These methods have been used to produce a
number of vaccines,
12. Further Developments in Vaccine Production
Improvements in using attenuated
pathogens as vaccines have been made
available through developments in rDNA
Tech.
Using these methods, defined genetic lesions can be
introduced into pathogens to specifically attenuate
them (e.g. in Salmonella and Cholera).
Future directions also include recombinant vaccines
where genes encoding protective antigens from
pathogens are engineered by recombinant DNA
technology into existing attenuated virus or bacteria
which act as carriers.
13. Viruses
• Vaccinia : the first recombinant virus was
produced and tested in 1982.
Since then it has been extensively used as a
recombinant carrier for over 100 different antigens.
The extremely large genome of the poxviruses has
facilitated the insertion of larger parasite and
bacterial genes into Vaccinia.
NYVAC, a highly attenuated form of Vaccinia, has
been used as a recombinant carrier for HIV vaccine
and clinical trials are underway.
Constructs have also been made incorporating
cytokine genes (ALVAC). (see Letvin, Science (1998)
280 (Jun 19) 1875-80)
14. Adenovirus
have also been used as a carriers for HIV
vaccines, but with limited success.
This is probably due to the highly cytolytic
nature of adenovirus. Letvin, Science
(1998) 280 (Jun 19) 1875-80)
15. Bacteria
• BCG : Used in vaccines against: Malaria (Merozoite surface protein -
1), HIV-1 (Letvin, Science (1998) 280 (Jun 19) 1875-80), Borrelia
burgdorferi and Streptococcus pneumoniae
• Salmonella : The EvansTy21a attenuated strain used in vaccines
was produced by chemical mutagenesis. Recently, aro mutants, which
lack enzymes involved in the production of aromatic amino acids have
extensively studied as genetically attenuated alternative and as carrier
for other vaccines (reviewed Chatfield et al.Vaccine (1989) 7, 495-498).
• Cholera : The Cholera toxin A (CTA) subunit has ADP ribosylating
activity and is responsible for Cholera induced diarrhoea. The CTB
subunit is highly immunogenic, especially when given orally. Attempts
to produce a vaccine have therefore concentrated on attenuating the A
subunit (clinical trials with CVD103Hg-R are underway)
• Bordetella pertussis: intranasal administration of a recombinant
vaccine encoding the 28-kDa glutathione S-transferase antigen from
Schistosoma mansonii has been demonstrated to mediate protection
to infection.
16. Problems associated with attenuated vaccines:
• undefined genetic lesions (not the case with
genetically attenuated vaccines)
• possibly of reversion to virulence/toxicity (e.g.
in HIV/SIV vaccines: Johnson, Nature Medicine
(1999), 5(2), 154-155)
• cannot be used in immunocompromised hosts
• possibility of zoonosis
• loss of replication due to interference by other
infections
• public acceptance of genetically modified
vaccines
17. Subunit vaccines
A number of subunit vaccines are already
licensed for use (See Section 2) and interest
in producing new subunit vaccines continues,
mainly due to safety concerns. For example,
the immunogenicity and toxicity of
Bordetella pertussis vaccine, an inactivated
whole cell vaccine is greatly affected by
culture conditions. Therefore development of
acellular whooping cough vaccines,
containing pertussis toxin and fimbral HA,
are of interest.
18. Recombinant subunit vaccines
To avoid the problems involved in bulk
culture of pathogens and to increase the yield
of protective antigens, recombinant vaccines
have been introduced.
Hepatitis B was the first recombinant vaccine
licensed for human use.
The surface antigen (HBsAg) was expressed
in yeast, the antigen thus produced
spontaneously forms multimeric particles
similar in appearance to the non-infectious
Dane particles produced during hepatitis
infection.
19. Recombinant plant vaccines
Hepatitis B surface Ag expressed in
potato/tobacco is immunogenic when fed to
mice.
This has also been the case when Cholera toxin
B subunit and E.coli enterotoxin B subunit (LT-
B) were expressed in plants.
Furthermore, a clinical trial of LT-B expressed
in potato (Tacket et al.Nature Medicine 1998, 4
(May), 607-9), demonstrated that
administration of 3 doses of 50g of potato (4 -
15 ug of LT-B) produced :
20. antibody secreting cells in
peripheral blood circulating IgG
induced to LT-B (91% had 4-
fold increase - 1 non responder)
73%
developed
neutralising
Ab
55% had 4
fold
increase in
serum IgA 50% in
secretory
IgA
21. Peptide Vaccines
Whole proteins only contain a handful of
protective epitopes, these can be
synthesised and produced in large scale by
peptide synthesis techniques.
Information from the primary sequence of
proteins can be used to predict which
sequences may be T cell epitopes.
Relative merits of peptide vaccines
22. Advantages Disadvantages
• Chemical purity/safety • Need to know amino acid sequence
• Unlimited source of material • Need to identify of T and B cell
epitopes
• Costs • Genetic restriction of T cell
recognition
• Stability, storage and delivery • Lack of Immunogenicity
• Defined immunogen
• Exclusion of adverse epitopes
23. Adjuvants
One approach to increase the immunogenicity of a protein is to
formulate it with a vaccine adjuvant. Adjuvants are described in the
Dictionary of Immunology as "Agents which act non-specifically to
increase the specific immune response or responses to an antigen"
or alternatively "the immunologists dirty little secret" by Charles
Janeway.
Essentially, adjuvants appear be able to provide signal 2 to T cells,
a feature absent in purified proteins. The effects of adjuvants are
mainly mediated indirectly via antigen presenting cells.
The only adjuvant currently licenced for use in humans in the UK
are the Aluminium compounds. Their adjuvant activity was first
described in 1926 and they form a component of vaccines against
Hepatitis A, Hepatitis B, Anthrax and DTP (Diphtheria, Tetanus,
Pertussis).
However one of the major limitations of Aluminium compounds is
that they only stimulate the induction of Th2 responses. In contrast
some experimental adjuvants (such as Freund's Complete Adjuvant
(FCA)) can stimulate Th1 responses, but are too toxic to be used
clinically.
24. The ability to modulate Th1 or Th2 responses, has been assigned to a
third signal in T cells, therefore adjuvants can clearly influence the
provision of signal 3. This is a major problem as induction of Th1
responses are thought to be required for vaccine induced protection
against the big 3 pathogens (HIV, Tuberculosis and Malaria). Therefore
a number of new adjuvants are under development by various
companies and institutes to try and induce strong antigen specific Th1
responses to vaccines.
Particles
Liposomes (Swiss Serum and Vaccine Institute)
These are composed of lipid bilayers (like plasma membranes) which can have
antigens entrapped inside
ISCOMs
These contain a glycoside extract (Quil A) prepared from tree bark. When mixed
with virus spike proteins (surface proteins) they form micelles
Bacterially derived adjuvants
Monophosphoryl lipid A (SKB)
Is a relatively de-toxified derivative of lethally toxic endotoxin from gram
negative bacteria (LPS)
Natural/Synthetic surfactants
QS21 (SKB)
A more purified version of Quil A, but not micellar like ISCOMs
Oil/Water emulsions
MF-59 (Chiron)
These adjuvants are highly diverse
25. DNA vaccines (Genetic Immunisation)
Previous studies have used molecular biology to express genes
encoding protective antigens in expression vectors. These antigens,
such as the Hepatitis B vaccine expressed in yeast cells, are then
isolated and used as vaccines. More recent approaches have used
naked plasmid DNA containing genes encoding the protective
antigen to actually transfect the host. A typical plasmid vector such
as pcDNA, contains strong promoters to induce transcription of the
protective antigen DNA. Host cells then express the protein antigen
in situ, and host immune responses are generated to the foreign
protein. Methods used to introduce DNA include :
Intramuscular injection
Intradermal injection
Gene Gun
DNA bound to gold particles and shot under gas pressure at high speed into
epidermis
Jet injection
Using even higher pressure and speed, it is possible to shoot DNA (or
proteins) into epidermal cells without the requirement for gold particles
26. DNA vaccines have been applied to numerous
infectious agents
DNA vaccines have been applied to
numerous infectious agents and has been
frequently successful in the mouse. This is
partly due to plasmid DNA having its own
built-in adjuvant. Prokaryotic DNA
contains CpG motifs which are largely
absent in mammalian DNA, however,
CpGs are recognised as foreign by the
mammalian immune system and directly
activate it.
27. Advantages Disadvantages
Simple : Doesn't require an expression system
Limited effectiveness
in human trials
Has its own inbuilt adjuvant (CpG)
Lack of control of
antigen expression:
Low doses of antigen
could lead to tolerance
or Th2 induction
Long term stimulus from a single injection (not
intramuscular injection)
Questions over
integration of plasmid
DNA
Effective (in mice, less so in humans, although this
may be due to characteristics of CpG flanking
sequences)
Public acceptance
Can express multiple antigens in a single plasmid
Can include adjuvants in plasmid, e.g.
• genes encoding costimulatory molecules
• genes encoding adjuvant active cytokines (eg. IL-12)
• genes targetting antigen localisation in APCs (e.g. to
Class II compartments)
28. Experimental Approaches to
Vaccine Development
With our expanded understanding of how the
immune system works, experimental approaches
to vaccine development are aimed at developing
vaccines that target protective immune
responses. One area of interest is the
development of better vaccines to stimulate
mucosal immunity, since most pathogens enter
the body through mucosal membranes. The oral
polio vaccine is an example of a vaccine that
enters by the pathogen's normal route and
stimulates protective neutralizing antibody.
Difficulties with oral vaccine administration
include antigen destruction in the stomach or
intestines and risk of inducing tolerance.
29. Another area of vigorous research is targeting antigens
to APC. Antigens have been covered with mannose to
bind macrophage mannose receptor and made into
immune complexes to stimulate uptake by FcR+ cells.
Pathogen DNA has been complexed with CTLA-4 to
promote its uptake and expression by B7+ APC.
ISCOMs target antigen to Class I MHC, while antigen
coupled to a particular signal peptide can be used to
move antigen into endosomes for processing and
presentation on Class II MHC. The outer membrane
protein of Salmonella typhimurium binds M cells and
may be useful for targeting antigen to the mucosal
immune system.
30. Finally, the ability of vaccination or cytokine
administration to control ongoing infection is
being studied. Chronic infections occur with
Herpes simplex viruses, hepatitis B and C
viruses, Mycobacterium tuberculosis and M.
leprae, and the parasites Leishmania,
Plasmodium, and Schistosoma. Persisting
infections lead to prolonged infectivity, tissue
damage from immune hypersensitivity, and
tumor development. Established immune
responses are very difficult to modify or
eliminate; but there is hope that with a properly-
targeted vaccine boost the immune system may
be able to completely eliminate pathogen.