vaccines case Flashcards
what is meant by individual protection?
- Most countries have recommended routine vaccinations for their citizens
- Vaccination’s primary purpose is to protect the individual from infectious diseases that can cause significant harm
what is meant by community protection?
- Vaccinated individuals are less threat to others, disease can’t spread so much, reduces outbreaks
- If enough members of the population are vaccinated, you can eradicate the disease completely from that community
- This is called ‘herd immunity’ (aka population or community immunity). Protects the wider populations and less outbreaks within communities
what is small pox?
- Variola virus, highly contagious, caused plagues for centuries
- Blistering rash, blindness, arthritis
- Mortality 30-50% from variola major strain
- Since 900s in Eastern Asia ‘variolation’ was practised using smallpox scabs. Try to inoculate them by trying to put the virus under the skin or up the nose
- Not introduced in the West until 1700s
what is cow pox?
- Vaccinia virus, related to smallpox but causes milder infections (orthopoxvirus family)
- Dr Edward Jenner - noted dairy milkmaids contracted cowpox but not smallpox
- Inoculated a boy with cowpox, once mild infection cleared, he later inoculated him with smallpox twice – no reaction
WHO small pox eradication programme
World Health Organization, 8 May 1980
• Eradicated worldwide
• Return of the virus is unlikely
what are the problems with vaccination programmes?
can’t vaccinate everyone against every infectious disease.
what are the Joint Committee on Vaccination and Immunisation (JCVI)
- Specialist branch of Public Health England
- Responsible for monitoring and updating the vaccination schedule
- Make recommendations to government about all matters relating to vaccination
- Publish and update ‘The Green Book’
what is the NHS schedule
- Groups are targeted according to susceptibility and risk
- Babies at 2,3 and 4 months old need a range including: diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type b, hepatitis B pneumococcus, rotavirus, meningitis b
what are the factors in deciding who gets a vaccination?
• The JCVI take many things into account when deciding, they relate to:
– The susceptible populations
– The diseases themselves e.g. HIV vaccine
– Pharmaceutical issues and the vaccine products
the factors in a population in deciding if gets vaccine
- Age – babies lack immunity, older people’s immunity declines over time
- Risk category – some people more at risk of serious illness than others e.g flu in pregnant women, people with co-morbidities
- Social changes – children starting school, or young adults starting university
- Public/media campaigns/new research
how does disease determine who gets a vaccine
- Prevalence of organisms and environmental factors e.g. flu in the UK
- Sudden outbreaks of a disease
- Desire to increase herd immunity
- Prevention of other risks related to the diseases e.g. more serious complications
how does pharmaceutical determine who gets a vaccine • Costs of mass manufacturing versus effectiveness of vaccine programme
• Antigenic drift or shift meaning new strains become prevalent
• If vaccine product is able to be produced – none so far for HIV, malaria: world’s first 2018
• Sometimes need to produce a vaccine quickly due to sudden pandemics…like COVID-19
what are risk associated with vaccines
- Mild illness, fever and rashes
- Pain, redness, swelling, tenderness at injection site
- Vaccine failure, insufficient immune response
- Small anaphylaxis risk – MHRA data suggests incidence of 1 per million doses approx
- Can be related to excipients or antigen e.g. ovalbumin (relevant in those with egg allergy)
what are the benefits associated with vaccines
- Saves lives
- Herd immunity benefits for those who can’t be vaccinated or are more vulnerable e.g. infants, elderly, pregnant women, immunosuppressed
- Eliminates the disease in some cases
- Easier, safer, a lot more convenient than contracting the disease and having to treat it
what is the global situation on vaccines
- WHO monitors vaccination use globally
- Schedules vary, may include vaccines for diseases specific to the geographical area
- Access to vaccination is a health inequality problem in some parts of the world
what is meant by immunity?
• Immunity = ability of the human body to protect itself from infectious disease
• Two main groups of defence mechanisms in the body :-
1. INNATE (non-specific, non-adaptive) mechanisms
2. ACQUIRED (specific, adaptive) mechanisms
how does the innate mechanism of immune defence work?
blocks infection by utilising barriers of entry eg skin, tears, mucus, stomach acid
how does the adaptive immune defence system work?
if the innate defence fails to work, it destroys invaders such as cellular factors, natural killer cells, phagocytic cells and soluble mediators. if that fails this triggers the adaptive immune system (APCs with induce antigen specific fragments in MHC activate t-cells and b- cells to control infection and produce memory cells
give examples of passive and active naturally acquired immunity ?
active- infection contact with pathogen
passive- antibodies passed from the mother to the baby through breastfeeding
give examples of active and passive artificially acquired immunity
active - vaccine- dead or attenuated pathogens
passive -injections of immune serum (gamma globulin)
what is meany by acquired immunity
• Acquired immunity usually specific to a single organism or group of closely related organisms (share common ANTIGENS – ie Cowpox/Smallpox) because you have contact with the pathogen
what is meant by active acquired immunity?
- Produced by individual’s own immune system - usually long-lasting
- Involves CELLULAR RESPONSES (“cell-mediated”), HUMORAL RESPONSES (“antibody mediated”) or a combination of both acting on the infecting organism
- Can be acquired by NATURAL DISEASE or by VACCINATION
- Vaccines provide immunity similar to that provided by the natural infection, but without the risk from the disease or its complications
how does the adaptive immune system work CD4 lineage ?
antigen presenting cells sees antigen
which chops it up and present it as peptides with MHC11 to naive CD4+ t-helper cells
which becomes effectors t- cells of 4 basic types
how does the adaptive immune system work for CD8 lineage?
antigen presenting cells (usually dendritic cells) see antigen (usually virus)
chops it up and present it peptide with MHC1 to naive CD8 cells
which become cytotoxic t -cells
which produce cytotoxins or triggers apoptosis of the target cells
to continue cytotoxic t- cells production and create memory cells. antigen presenting cells must interact with activated CD4 t- cells
how does the body develop immunity?
the bodys adaptive immune system can learn new invading pathogens.
describe an immune response?
specialised antigen cells engulf the virus and display portions to it to activate t- helper cells
t-helper cells enable other immune responses
B cells make antibodies that can block the virus from infecting cells as well as mark the virus for destruction .
cytotoxic T cells identify and destroy virus infected cells
long lived memory b and T cells that can recognise the virus and produce antibodies against the virus quicker therefore providing immunity
what are the 4 ways that antibody mediated immunity - humeral response work?
blocking binding of pathogen to cell surface receptor= neutralising antibodies
targeting CLTs to infected cells
coating- pathogens and targeting them for phagocytosis
antibody- antigen complexes activate classical complement cascade which leads to destruction of pathogens by phagocytosis or bacterial membrane attack
what is meant by cell mediated immunity?
• CMI provided by EFFECTOR lymphocytes (“T cells”) of Th1 type (includes CD8+ CTLs)
• TWO principal classes – each has specific function:-
1. CD8+ T-cells (Cytotoxic (killer) T-lymphocytes = “CTLs”) - recognise and destroy infected cells
2. CD4+ Th1 T-cells (“Th1 cells”) – activate phagocytic macrophages to destroy and engulf bacteria
• Th1 cells activate macrophages by CYTOKINES, principally IFN-ϒ
name the different subtypes of antibody subtypes in protection?
IgM – major role in complement activation – limited role in neutralisation -INDUCED BY VACCINATION (primary response) - blood
IgG – SYSTEMIC (blood, tissues, lymph) - ALL major roles (neutralisation, ADCC, opsonisation, complement activation)- PRIMARILY INDUCED BY VACCINATION
IgA – principle isotype in SECRETIONS at MUCOSA (gut, respiratory tract, genital)
- Less potent opsonin, weak activator of complement – STRONG viral neutraliser
- CAN BE INDUCED BY VACCINATION (BUT NEEDS SPECIFIC ADJUVANTS/ROUTE
what is meant by passive acquired immunity
- Passive immunity = protection provided by transfer of ANTIBODIES from MOTHER, most commonly across the placenta (IgG) and (to some extent) from breast milk (secretory IgA) to CHILD
- Most infant deaths from PERTUSSIS at <3mo, so mother should be vaccinated to protect neonate; RUBELLA can severely damage foetus, so mothers can be offered MMR if not previously vaccinated ; pregnant women also have increased risk of death from INFLUENZA if not vaccinated [these three vaccines offered on NHS schedule]
- PROTECTION PROVIDED BY MTC TRANSFER IS TEMPORARY – FEW WEEKS OR MONTHS – neonate (1-28 days of life) very vulnerable to disease and protected by maternal antibodies. As healthy immune system dependent on nutritional status – mum should eat well too
how do vaccines protect us via acquired immunity?
- Vaccines produce their protective effect by inducing active acquired immunity and providing immunological memory
- Immunological memory enables the immune system to recognise and respond rapidly to exposure to natural infection at a later date and thus to prevent or modify the disease
- Thus, key to an effective vaccine is ability for it to TRIGGER PROLIFERATION OF NAÏVE T-CELLS
- Success depends on whether Th1 and CTL responses are induced (predominantly against INTRACELLULAR ORGANISMS)
- Or Th2 ANTIBODY responses are induced (predominantly against EXTRACELLAR ORGANISMS)
what are the two ways in which memory cells are made?
naive T- cells proliferates in response to antigen forms effector cells and memory cells which wait for future infections
naive B cells do the same with the help of t- cells from plasma cells to deal with current infection but also memory cells which also wait for future infections
what are the roles pf adjuvants?
• Soluble proteins often poorly immunogenic when used on their own as a vaccine
• Adjuvants = compounds that enhance IMMUNOGENICITY of protein antigens
• Two broad groups (base on mechanisms):-
1. Particulate vaccine-delivery systems target antigen to antigen presenting cells (APCs).
Convert soluble proteins into particles (APCs) – ie: alum (adsorbs proteins),
mineral oils (MF59 - emulsifies proteins), Quil A detergent (forms colloids with proteins) –
APCs preferably recognise and process particles (like viruses, bacteria etc)
2. Immunostimulatory adjuvants - directly activate APCs through specific receptors
(e.g. toll-like receptors (TLRs) - resulting in inflammatory responses that amplify the innate
immune response)
Active research field – many APC receptors now mapped and ligands identified – provides
Co-stimulatory signals to activate T-cells (along with MHC + antigen peptide)
New generation ligands can be used to “skew” adaptive immune response to Th1 or Th2 –
optimises immune attack on specific pathogens
what are the principles of safe and effective vaccinations?
- EITHER search for (or create) ATTENUATED ORGANISMS with reduced pathogenicity to stimulate protective immunity…
- OR INACTIVATE (KILL) organisms – will NOT cause lethal systemic infection in the immunosuppressed
- NOW use purified COMPONENTS of whole organisms containing only KEY ANTIGENS OR NUCLEIC ACIDS that simulate protective immunity
what are the requirements for an effective vaccine
- IT DEPENDS ON THE ORGANISM
• INTRACELLULAR organisms usually need CTL and Ab
• EXTRACELLULAR organisms usually Abs - IT PROVIDES DEFENSE AT POINT OF ENTRY
• Stimulation of MUCOSAL IMMUNITY may be required at specific mucosa (gut, respiratory epithelia, genital epithelia) - PRE-EXISTING ANTIBODY MAY BE REQUIRED
• Pre-existing antibody protects against diptheria/tetanus
exotoxins – forms antigen: antibody complexes which are phagocytosed
• Polio and HIV enter cells shortly after infection – antibodies
must be ready to BLOCK viral ligand:cell receptor interaction - PROTECTION OPTIMISED WHEN SPECIFIC EPITOPES RECOGNISED
• Immune responses directed at multiple epitopes
• Not all of these generate protective Abs or CTLs
• Some may even generate suppressor T-cells
• Thus, CORRECT EPITOPES must be targeted - IT MUST BE SAFE
• Millions immunised – very low toxicity
• “Cutter Incident” – IPV contained live
virus – hundreds paralysed, 10 deaths - MUST PROTECT MOST VACCINEES
• Rapid generation of herd immunity
• Reservoir of susceptible falls – transmission drops
• Confidence - MUST GENERATE LONG-LIVED IMMUNITY
• Repeated booster immunisations often impracticable
• Cheaper, improves population health - IT MUST BE CHEAP
• Will be administered to large populations
• Very cost-effective healthcare
• BUT benefit eroded if cost per dose rises
how do you optimise vaccinations strategies?
- Vaccination strategy greatly influences the immunogenicity, efficacy, and safety of a vaccine
- For any specific vaccine product, vaccine immunogenicity and efficacy can be dramatically affected by the vaccination strategy used, including number of and interval between immunizations, use of prime/boost regimens and vaccine modulators (adjuvants)
- Good vaccination schedule requires a minimal number of doses and an optimal interval between immunizations [think of COVID]
- Most currently licensed vaccines are administered either by intramuscular or subcutaneous needle injection, and require multiple doses to elicit an adequate antibody response with an interval variation between 4 weeks and 6 months
- Due to the complexity of different types of vaccines, there is no standard universal formula that can be used to determine an appropriate vaccination strategy
- However, it is important to understand the impact of vaccine administration parameters on immunogenicity and efficacy – not optimised for COVID
- See THE GREEN BOOK for optimised strategies for NHS Vaccines
what does life long vaccinations depend on immune status?
LIFE-LONG VACCINATION IS DEPENDENT ON IMMUNE STATUS
what are routes of administration in general
- Oral route: administered by mouth (per os)
- Subcutaneous route: injected into the area just beneath the skin into the fatty, connective tissue (sc)
- Intramuscular route: injected into muscle tissue (im)
- Intradermal route: injected into layers of the skin (id)
- Intranasal route: administered into the nose (in)
- NOT intravenous - generally leads to a relatively low immune response compared to other injection routes and can also cause anaphylaxis, including allergic reaction and toxicity
PARENTERAL VACCINATION
• Parenteral vaccine administration - three major routes: intramuscular (IM), subcutaneous (SC),
intradermal (ID) inoculation
• The relative immunogenicity of vaccines by these three routes (IM, SC, and ID) can vary,
depending on individual vaccines
• In general, ID immunization generates greater immune responses than IM injection
• Presumably, the reason for this may be that the dermis contains more dendritic cells (DCs)
which facilitate the capture of antigens, and local inflammation induces maturation of the DCs
and their migration into draining lymph nodes BUT may be difficult to administer (particularly
in children)
• Intradermal vaccination has been used for populations that do not respond well to an IM injection, such as the HBV vaccine in dialysis patents
• SC and IM immunizations induce very similar responses in clinical studies – less toxicity/anaphylaxis via IM (especially if using adjuvants) and easier to do then ID or SC
ROUTES OF ADMINISTRATION – MUCOSAL VACCINES
• Most vaccines given by i.m injection
• PRACTICAL aspects of this – painful, expensive (needles,
syringes, injector), unpopular (reduces uptake) , mass vaccination (laborious)
• IMMUNOLOGICALLY, may not stimulate optimal immune response - MOST pathogens enter via MUCOSA
• Ie: Gut (Vibrio cholerae, Shigella spp., Salmonella typhi, E.coli 0157): Respiratory mucosa (SARS-CoV-2, Flu, rhinovirus, Streptococcus pneumoniae, Mycobacterium tuberculosis); Genital/anal mucosa (HIV, bacterial STIs, Chlamydia)
• If given ORALLY or NASALLY, overcomes many issues
• Polio eradication campaign success due to simplicity of OPV – few drips into mouth or on a sugar lump
• Live paediatric flu vaccine given nasally
• ADJUVANTS can play key role in directing response to appropriate mucosa (ie: chitin in nasal vaccines)
what is meningitis
- Meningitis is defined as being ‘inflammation of the meninges’.
- The meninges are the three membranes which enclose the brain and spinal cord.
- Meningism refers to the signs and symptoms that accompany the inflammation.
What causes meningitis?
what causes meningitis?
Meningitis can be caused by a variety of agents: Microbial agents • Bacteria-Neisseria meningitis • Viruses • Fungi • Protozoa (very rarely) • What else?
who is at risk of meningitis?
Everyone! But particularly,
• babies and young children. Babies haven’t acquired a strong immune system.
• teenagers and young adults
• elderly people
• people with a weak immune system – for example, those with HIV and those having chemotherapy
