Vaccines 2 Flashcards
The start of vaccine success
1950s onwards: start of co-ordinated vaccine programmes. 1970s: WHO launches Expanded program on Immunisation. 2-3 million lives saved a year. Reduced mortality in children and incidence of many diseases responsible for child deaths.
Factors effecting vaccine protection
Age: Highest burden of infectious disease in first 5 years, induction of immune response challenging in first year, limited protection/ duration in over 75s. Vaccination schedule: Children receive large numbers of vaccines in the 1st 12 months: fitting a schedule is difficult with vaccines rarely delivered on time. Access to vaccines. Anti-vaccination movement. Commercial viability. Immunological challenges.
Case studies - Polio symptoms, clinical presentation and erradication
- Highly infectious
- Mainly affecting under 5s
- Symptoms: fever, fatigue, headache, vomiting, neck stiffness, paralysis
Since 1988 - 99% reduction in cases - Total eradication would save 40-50 billion
TB- BCG vaccine
Introduced in 1921
▪ Live attenuated vaccine: Mycobacterium bovis, Repeatedly sub-cultured in the lab until no longer causes
disease in humans
▪ >3 billion people have received BCG vaccine
▪ Variable efficacy: Strain variation, Batch variations, Administration
▪ Protective for 10-20 year
Case study: Polio vaccines
Salks inactivated virus
Sabins live attenuated virus
Sabin (oral vaccine) most effective at preventing infection/ creating immune response but poses risk of pathogenic reversion.
Both protect against all 3 polio virus serotypes
WHO declared wild poliovirus type 2 eradicated in April 2016
TB - cause, prevalence and treatment
- Caused by Mycobacterium Tuberculosis
- Est. 10 million cases 2019
- 1.4 million people died from TB in 2019
- > 200,000 people with MDR/RR-TB
▪ 30 countries account for 87% of cases
▪ Treatable with antibiotics
▪ HIV patients 18 times more likely to develop active
TB
Measles - clinical presentation and symptoms
- Highly contagious
- Rash, high fever, cough, runny nose, teary/inflamed eyes
- Complications include seizures, pneumonia, blindness, inflammation
of the brain - Measles attacks memory T cells so may cause loss of immunity to
other diseases
Measles - Case prevalence
▪ Global measles cases: estimated 9,828,400 in 2019
▪ Global measles deaths: estimated 207,500 in 2019
▪ During 2000–2019, compared with no measles vaccination, measles
vaccination prevented an estimated 25.5 million deaths globally
Measles-Mumps-Rubella (MMR) Measles vaccine
- Live, attenuated vaccine
- Licenced since 1971
- Two doses: 12-18 months 3-6 years
- Contraindication: Pregnancy, immunocompromised
MMR- Autism scandal
- Link to autism suggested by Andrew Wakefield in the Lancet 1998 and received widespread press. Work was discretised, struck off the medical register. Misinformation widespread on internet, Anti-vaxxer movement, public concern about vaccine safety
SARS-CoV-2? COVID 19 global stats
Globally: 775 million cases, 7 million deaths, 13.6 billion vaccinations, 5.3 billion people fully
vaccinated
Critical antigen of COV viral protein
Critical COV antigen: Spike (S) protein (red) binds to ACE2
receptor on host cells: critical role in virus attachment to and entry into host cells. Antibodies against this
block infection.
Pfizer/BioNTech
mRNA vaccine containing mrna of receptor binding domain of the S-protein encapsulated in lipid nanoparticles: protects mRNA, Delivers to host cells. Cells produce S-protein via protein synthesis triggering innate and adaptive immunity. Adv: >90% efficiency, fast and cheap to manufacture, relatively minor side effects. DisAdv: Unstable at room temp
Oxford/AstraZeneca
S-protein cloned into an adenovirus with vector modified to prevent replication but mimic infection. Enters cells and cells use genetic information to produce S-protein. Adv: stable in a fridge, relatively minor side effects. DisAdv: Variable efficacy against variant strains.
SARS-CoV-2 variants and their effects on viral efficacy
Vaccines based on first SARS-CoV-2 sequence (Wuhan-1). Mutations can change the properties of the virus, e.g: N501Y – enhances binding affinity to ACE2. E484K – escape from neutralising antibodies.