Vaccination against Disease Flashcards
What causes smallpox?
Variola virus (orthopox virus)
What is variolation?
Exposing people who have never had smallpox to material from smallpox sores (pustules) by scratching the material into their arm or inhaling it through the nose
What happens after variolation?
People usually develop symptoms associated with smallpox e.g. fever and rash
Why is variolation done?
Fewer people died from variolation compared to if they had acquired smallpox naturally
What were the findings of Edward Jenner in 1796?
He observed that milkmaids were generally immune to smallpox
Postulated that this was due to the pus in the blisters milkmaids received from cowpox, which protected them from smallpox
Tested this hypothesis by inoculating 8yo James Phipps with pus from cowpox blisters on the hands of milkmaid Sarah Melmes who had caught cowpox
Jenner exposed Phipps several times to variola virus but he never developed smallpox
What was used to develop the first vaccine against smallpox?
The Vaccinia virus which is closely related to cowpox
When was the world declared free of smallpox?
1980
Why was smallpox eradication possible?
No animal reservoir for smallpox
Infection created natural life-long immunity
Subclinical cases are rare
No prodromal phase
Variola virus has only 1 serotype (all strains are covered by the vaccine)
Vaccine has good effectiveness
Major commitment by WHO and governments
What are the aims of vaccination?
Protection of individuals
Reduction of disease burden
Protection of populations - herd immunity
Eradication of the microbe
Block transmission without protecting host
Post exposure prophylaxis
Describe the immune response to vaccines
Vaccine is taken up by phagocytic cells
APCs become activated and migrate towards lymph nodes
Vaccine Ags are presented to lymphocytes, which activate and proliferate, producing antigen-specific B and T lymphocytes
Memory B and T cells are formed that provide long term (sometimes life-long) protection against infection
What is active immunity?
Protection produced by an individual’s own immune system
Usually long-lasting (immunological memory) but takes time to develop
How is active immunity acquired?
Natural disease or by vaccination
What does active immunity involve?
Cellular and humoral responses acting against one or more antigens on the infecting organism
What is passive immunity?
Protection provided from transfer of Abs from immune individuals:
- across the placenta
- blood transfusions
- immunoglobulins
- monoclonal abx
Describe maternal abs
Mother to child protection from placental transfer
More effective against some infections e.g. tetanus and measles than for others e.g. polio and whooping cough
What are the downsides of passive immunity?
Short term - temporary protection lasting commonly for a few weeks or months
Does no induce immunological memory
Types of active immunity
Natural - own abs from becoming infected
Artificial - vaccination
Induces immunological memory and long-term protection
Types of passive immunity
Natural - maternal abs
Artificial - monoclonal abs
No immunological memory, short-term protection
What is herd immunity?
Indirect protection from a contagious infectious disease that happens when a population is immune either through vaccination or immunity developed from previous infection
How does herd immunity protect individuals?
Even people who are not vaccinated or in whom the vaccine does not induce immunity are protected because those around them who are immune act as buffers between them and an infected person
How is herd immunity ensured?
The more infectious a disease, the greater the population immunity
What is the purpose of herd immunity?
Protects those who are unable to build up immunity, such as people with immune deficiencies or whose immune systems are being suppressed for medical reasons
When herd immunity is well-established, unvaccinated people benefit from everyone else getting vaccinated without needing to vaccinate themselves
What are the types of vaccines?
Can be monovalent (for single strain) or multivalent (for multiple ags, strains or microorganisms)
Inactivated
Attenuated
Toxoid
Subunit
Conjugate
Heterotypic/Jennerian
Describe inactivated vaccine
Whole microorganism destroyed by heat, chemicals, radiation or antibiotics
Used for influenza, cholera, buubonic plague and polio
Describe attenuated vaccine
Live microorganisms modified to be less deadly or closely-related microorganisms that induce immunity by provoking better immune response but dangerous for immunocompromised patients
Used for yellow fever, measles, rubella, mumps, tb
Describe toxoid vaccine
Inactivated toxic compounds
Used for tetanus, diphtheria, snake bites
Describe subunit vaccines
A protein component of the microorganisms
e.g. surface proteins or synthetic virus-like particles lacking viral genetic material so unable to replicate
Used for hepatitis B and HPV
Describe conjugate vaccines
Polysaccharides on bacterial outer coats that poorly stimulate the immune system (poor immunogen) paired with a protein that is highly immunogenic (an adjuvant)
Used for Haemophilus influenzae type
Describe heterotypic/Jennerian vaccines
Pathogens that infect other animals but do not cause disease or cause mild disease in humans like cowpox
Used for tuberculosis (Mycobacterium bovis , BCG)
What is a live attenuated vaccine?
Live but weakened (attenuated) pathogen
Immune system responds similar to in natural infection
What is the response to a live attenuated vaccine?
Immune system responds similar to in natural infection
Full, long-lasting ab response after 1 or 2 doses
What is the risk of using live attenuated vaccines?
Pathogen can multiply and cause disease in those with weak immune systems
What are live vaccines currently available in the UK?
Live influenza vaccine (nasal)
MMR
Rotavirus
Varicella
Shingles
BCG (TB)
Oral typhoid
Yellow fever
What are general contraindications to vaccines?
Previous anaphylactic reaction to vaccine or component - very rare, allergens can include eggs, antibiotics e.g. neomycin, gelatine, latex, polyethilenglycol
What are contraindications to live vaccines?
Primary/acquired immunodeficiency
Patients on immunosuppressive medication
Pregnant women
Infants born to mother who received immunosuppressants during pregnancy
Those in contact with an individual with immunodeficiency or on immunosuppressants - replicating viruses can be transmitted from vaccinated to immunosuppressed individuals
Describe the MMR live vaccine
Single dose is at least 95% effective in preventing clinical measles
Single dose confers close to 100% protection against lab confirmed rubella
Single dose confers between 61-91% protection against mumps
What are killed (inactivated) vaccines?
Contain whole virus particles that have been killed or inactivated to prevent them from causing disease
Safe to use as virus does not replicate and cannot cause the disease they are protecting against
What diseases use inactivated vaccines?
Rabies
Polio
Hepatitis A
What is poliomyelitis?
Caused by poliovirus
Spreads from person to person and can infect a person’s spinal cord, causing paralysis
Describe inactivated polio vaccine (Salk)
Killed virus
Prevents against disease
Subcutaneous (SC) or intramuscular (IM) administration
Humoral response (IgG)
No intestinal immunity (IgA)
Prevents paralysis but not re-infection
Longer shelf life
Currently in routine UK scehdule
Describe Oral polio vaccine (Sabin)
Liver attenuated virus
Prevents against disease
Oral administration
Humoral and intestinal immunity
Herd protection
May revert to virulent form and cause vaccine-associated paralytic polio (VAPP)
Describe subunit/recombinant vaccines
Specific part (antigen) not whole pathogen used
Often requires several doses to achieve good immunity
Many contain adjuvants (immunogenic substances) that enhance immune response e.g. aluminium in HepB vaccines
What do HepB vaccines contain?
Consist of recombinant HBsAg
Surface antigen gene isolated from hepatitis B virus and inserted into yeast
Modified yeast cells produce HBsAg which is used in vaccine
Pure HBsAg can be obtained from this
Why do we have polysaccharide conjugated vaccines?
Plain polysaccharide antigens do not stimulate the immune system as broadly as protein antigens such as tetanus or diphtheria, particularly in infants
To solve this, some polysaccharide vaccines have been enhanced by conjugation
What is conjugation?
Linking of polysaccharide antigen to protein carrier that infant’s immune system readily recognises to provoke an immune response e.g. diphtheria or tetanus toxoid
Describe the pneumococcal polysaccharide vaccine
Not effective in under 2yos, used in >65yo or high risk groups
Does not induce immunologic memory
Does not protect against non-invasive disease e.g. otitis media
Does not reduce nasopharyngeal carriage
Describe the pneumococcal conjugate vaccine
Effective in under 2yos
Induces immunologic memory
Protects against non-invasive disease
Reduces carriage thus induces herd immunity
What are toxoids?
Toxoid proteins are biologically inactivated forms of native toxins
How do toxoids stimulate an immune response?
They are adsorbed to an adjuvant to stimulate an immune response
How do toxoid vaccines work?
Induces anti-toxoid abs that are able to bind with the toxin and neutralise it (not the bacteria producing the toxins)
Booster doses are necessary after primary immunisation course
What do vaccine schedules depend on?
Prevalence of the disease
Available vaccines
Age specific risks for disease
Age specific risks for complication
Ability to respond to vaccine by age
Interference with immune response by passively transferred maternal ab in babies (blunting effect)
Describe the bivalent mRNA COVID-17 vaccines
Contain 2 different mRNAs that encode the COVID-19 spike protein - ancestral Wuhan strain and Omicron variant (BA.1)
