The Case Of The Vaccine Refuser + The Case Of The Misunderstood Disease Flashcards
The principle of vaccination are often …
misunderstood
The reduction in the number of cases of infectious diseases is testament to the incredible success of vaccination as a global … strategy.
The reduction in the number of cases of infectious diseases is testament to the incredible success of vaccination as a global preventative strategy.
What is a vaccine?
Usually, a vaccine is an agent causing a “pretend” infection that the body will fight
What are the advantages of vaccines? (4)
Can be administered at will and as required before an infection is contracted
Much lower risk and fare fewer side effects than the real infection
They prevent the real infection from occurring or reduce its severity and duration
Can be tailored to different target groups
Important requirements for vaccines
Must be safe to use and not cause the disease they aim to prevent
Must have minimal side effects
Must be long acting
Must be easy to store and transport
Must be cheap as possible
Basic types of vaccines
Active - causing the organisms to mount an immune response as if a real infection had taken place
Passive - providing the organisms with a ‘prefabricated’ immune response
Active and passive immunisation in history
Active vaccination practices in early 1700s in china - small amounts of pus from patients with small pox were used to inoculate others to prevent them from getting the disease
Edward Jenner and Small Pox
In the UK, Edward Jenner is credited with the foundation of modern vaccinology - used pus from a milk maid infected with cow pox to ‘vaccinate’ an orphaned boy - potentially lethal but he went ahead anyway and luckily the boy survived
Emil von Behring and passive immunisation - Diphteria
Horse anti-serum is used as a basis for preparing a medicine used for treating patients with diphteria, called diphteria anti-toxin
Horses injected with corynebacterium diphteriae toxin
Antitoxin prepared for human use from the horse serum
Passive immunisation - Horse serum for diphteria
Disadvantage - horse protein induces anti-antibodies in the patient, which beginning about a week to 10 days after inoculation will form complexes with the horse immunoglobin and inactivate it
These complexes can be deposited and cause secondary immune complex disease
Passive immunisation - Horse serum for diphteria (2)
Horse antitoxin is more rapidly eliminated than human antitoxin - half life of human IgG is about 20 days but than of horse antitoxin less than 5 days
Repeat administration of horse antiserum can cause severe ….
anaphylactic shock - today horse antiserum is still in use but will hopefully soon be replaced by human IgG produced in bio-reactors
Basic types: Live Vaccines
Also called ‘attentuated’; contain agents that have been weakened, but not killed
Attenuated agents cannot normally cause disease in healthy people, but can still replicate to produce a strong immune response
Basic types : recombinant and synthetic vaccines
DNA/RNA vaccines - various infections, cancer
protein/virus like particle - Hep B, HPV
Subunit vaccines - Hep B, TB (experimental stage)
Subunit/conjugate - HIB (polysaccharide plus protein)
Toxoid - Tetanus, Diphteria
Common passive vaccinations in practice
Hep B hyperimmune serum - post-exposure
Tetanus hyperimmune serum - post-exposure
Rabies hyperimmune serum - post-exposure
Anti-venoms, anti-toxins, etc - post-exposure
Hep A hyperimmune serum used to be given as exposure prophylaxis - now, an active, pre-exposure vaccine is available
VSV hyperimmune globulin is an effective prophylaxis for babies and mothers who develop varicella in a 1 week period before or after delivery
When do routine childhood immunisations start in the UK?
8 weeks old - schedule is updated to reflect changing needs and new vaccine developments
Live Vaccines should not be given to individuals who …
have a compromised immune system, because they could develop the disease the vaccine is designed to prevent
COVID-19 and vaccine development
Actual immune correlates or protection are still not fully understood, antibodies to the SARS-CoV-2 spike and nucleocapsid proteins appear to correlate with protection to a large extent
Interestingly, human coronaviruses causing the common cold seem to leave little immunity, however cross-reactivity appears to contribute to protection against covid in large parts of the population
A passive vaccine against COVID-19?
The SARS-CoV-2 spike protein can bind to ACE-2 and NRP-1 both of which are located at the cell surface
Regeneron Pharmaceuticals have developed an apparently effective antibody cocktail from recovered patients and humanised mice containing antibodies that recognise different receptor binding domain in a non-competitive fashion and abrogate binding
B-cells and antibodies: Therapeutics
Therapeutic antibodies recognising the spike protein are administered to individuals with COVID-19 to avoid serious disease courses
Treatment with REGN-COV2 resulted in a statistically significant reduction in the time-weighted average daily change from baseline in viral load from day 1 through day 7
Can be given to household members for protection - reduced the rate of symptomatic infection by 81% day 0 and 29
RNA-vaccines
Intracellular mRNA stability is achieved by:
a specially modified nucleotide positioned at the 5’ end (Cap)
A poly (A) tail (length)
The composition and structure of the 3’ untranslated regions (3’UTR)
good things about vaccines? (3)
prevent or reduce severity of infections can be tailored to different groups can be given in advance of an infection
requirements for effective vaccine (5)
safe, doesn’t cause disease minimal side effects long lasting easy to store/transport cost effective
patient’s own immune system is activated and the protection is usually life-long
patient’s own immune system is activated and the protection is usually life-long = active vaccination
patient receives immune factors from other organisms, own immune system doesn’t mount response
passive vaccination patient receives immune factors from other organisms, own immune system doesn’t mount response
Pros of live attenuated vaccines? (3)
strong rapid onset of immunity don’t need boosters
Cons of live attenuated vaccines (3)
potential for reversion to virulence virulence in the immunocompromised less stable in storage
Pros of inactivated vaccines (2)
no potential for reversion safe in immunocompromised
Cons of inactivated vaccines (3)
may need boosters slower onset of immunity Reduced degree of protection vs live.
examples of live attenuated vaccines (4)
MMR Varicella Influenza (some types) BCG
examples of inactivated vaccines (4)
pertussis poliomyelitis (Salk) influenza hepatitis A
examples of RNA vaccines?
COVID-19
Examples of recombinant vaccines (2)
hepatitis B HPV
Examples of passive immunisation (2)
anti-venoms tetanus hyperimmune serum
what vaccines are given at 12 weeks?? (3)
6 in 1 rotavirus pneumococcal
what vaccines are given at 16 weeks? (2)
what vaccines are given at 12 weeks?
what 5 vaccines are given at age 1?
MMR pneumococcal MenB MenC HiB
what vaccine is given every year aged 2-10?
flu vaccine
what vaccines are given aged 3 and 4 months?
MMR 4 in 1 booster
what jab is given aged 12-13?
HPV
what jabs are given aged 14?
MenACWY 3 in 1 booster
what type of vaccine are most of the covid vaccines?
what type of vaccine are most of the covid vaccines? RNA vaccines
how do RNA vaccines work?
stabilised mRNA molecules are transported into cells with liposome coating transcribed to make Covid protein
what is modified on mRNA for vaccines to make it more stable?
5’ cap polyA tail
advantages of RNA vaccines (4)
very safe effective few side effects production rapid
trained immunity theory about vaccines
vaccines or infections cause epigenetic reprogramming of immune cells so they respond better to infections
herd immunity
an infection is no longer transmitted across a population effectively as too many individuals are immune
R number - vaccines
reproduction number, the average number of cases of an infectious disease arising by transmission from a single infected individual
adjuvants
Chemical additives added to vaccines to improve effectiveness
what component actually causes most side effects of a vaccine?
adjuvants
6 in 1 vaccine contents
polio typhoid diphtheria tetanus whooping cough Hep b
which areas have a higher prevalence of HIV?
which areas have a higher prevalence of HIV sub saharan Africa
WHO strategy for HIV
90% know status 90% on treatment 90% suppressed
trend in AIDS related death globally
steady decline
where are the only places that HIV infections and deaths are increasing?
Eastern Europe Central Asia
5 key populations for HIV
sex workers clients of sex workers IVDU MSM transgender women
types of HIV?
HIV-1 and HIV-2
Which type of HIV is most prevalent globally?
HIV-1 type M
4 subtypes of HIV-1
M, N, O, P
where does HIV have the most genetic diversity?
central and Southern Africa
structure of HIV
ssRNA in an outer capsid in an envelope
key HIV membrane proteins …
key HIV membrane proteins gp120 gp41
key enzymes in HIV?
reverse transcriptase integrase
what receptors does HIV bind to?
CD4, CCR5 and CXCR4
life cycle of HIV
binding, fusion, uncaring, reverse transcription, transport into nucleus, transcribed, translated
what introduces diversity into HIV genome?
reverse transcriptase as it is error prone
Forms of HIV transmission (3)
blood exchange sexual contact vertical
what can increase risk of HIV transmission?
high viral load other STI so immune cells present
what is the risk of HIV transmission with blood exchange?
more than 90%
what happens to viral and T cells in acute HIV infection?
viral cells increase T cells sharply decrease
what happens to viral and T cells in asymptomatic HIV stage?
T cells stabilise and slightly recover viral cells decrease then stabilise
what happens to viral and T cells in AIDS stage of HIV?
T cells plummet, no recovery viral cells increase
how does starting ART impact T and viral cell levels?
viral cells decrease to undetectable T cells have good restoration
HIV reservoir
latent infection in memory CD4 cells maintained indefinitely, ART can’t affect it
how does recrudescence of HIV happen when people stop ART?
virus in HIV reservoir replicates and causes resurgence of infection
gut T cells in HIV
levels plummet and never fully recover, even on anti-retrovirals in a constant state of immune activation
what mediates initial decline in HIV cells?
HIV specific CD8 T cells
How does HIV viral load increase again during asymptomatic phase?
generates CD8 escape mutations e.g. by increasing glycosylation of envelope to hide
What allows opportunistic infections to occur? (HIV)
Decreased levels of CD4 T cells create susceptibility to various conditions that would not infect a “healthy” person
what happens as a result of constant immune activation in HIV?
increased pro-inflammatory cytokines, coagulation factors, immune system gets exhausted
HIV-associated neurocognitive impairment
involves various changes in the brain, among them generalized atrophy, edema (swelling), inflammation, and patches of demyelination HIV infection of astrocytes
HIV associated nephropathy
Infection of kidney epithelial cells by HIV and expression of HIV genes within infected kidney cells
what causes premature ageing and multi-organ disease in HIV?
permanent inflammatory state
symptoms of HIV in acute phase
flu-like symptoms
differentials for HIV (6)
EBV CMV Influenza lyme disease secondary syphilis SLE
AIDS stage of HIV defined as… CD4 COUNT OF
cd4 count of 200 or less
Opportunistic infection in AIDS
Pneumocystis jirovecii pneumonia (prev pcp) TB candida
Pneumocystis jirovecii pneumonia (prev pcp) =…
Pneumocystis jirovecii pneumonia (prev pcp) Opportunistic infection in AIDS
AIDS related malignancies (3)
- Kaposi’s sarcoma - Cervical cancer - Lymphoma
HIV indicator conditions
conditions that share risk factors or arise as a result of immunodeficiency
How can hepatitis C cause vasculitis?
leads to immune complex development that precipitates in vessels and causes inflammation
miR-122 and hepatitis C
a proviral factor that amplifies translation of Hepatitis C virus
how does HIV affect gut lymphoid tissue?
disrupts gut barrier so get more microbial translocation, persistent immune activation
