vaccines Flashcards
how many deaths are avoided because of vaccinations
Vaccines are hailed as one of the greatest global health achievements, avoiding an estimated 2-3 million deaths per year (WHO) and significantly reduce child mortality.
what is the purpose of vaccines
The primary purpose of vaccinations is to protect the individual from infectious diseases that can cause significant harm.
what is meant by herd immunity
When an individual is vaccinated, they become less of a threat to others as the disease cannot spread as widely, reducing outbreaks, reducing the reservoir of susceptible people, and ultimately leading to the eradication of the disease-causing agent – this is herd immunity. Herd immunity is extremely important as it protects those who are vulnerable or cannot be vaccinated (infants, elderly, pregnant women, immunosuppressed).
what kind of people are susceptible to diseases
Babies lack immunity, and older people’s immunity declines over time. Some groups are more susceptible to infectious diseases, or the risk of serious harm is higher; pregnant women and those with co-morbidities. Social changes, where one is introduced to a different environment or different people increases the risk of exposure to previously unseen infectious diseases; when children start school or young people start university, vaccines are recommended.
what are the side effects associated with vaccines
There are risks with vaccines. In most cases, the recipient will develop a mild illness in response to the vaccine (fever, rash) and pain or swelling at the injection site. Sometimes, the vaccine fails to give a sufficient immune response and in very rare cases (1 in a million), anaphylaxis will occur due to excipient or antigen related to allergen.
how is the prevalence of infection affected by the environment
The prevalence of an infectious disease is affected by the environment; in the UK, the influenza virus is common in winter because it thrives when temperatures are lower. Sudden outbreaks of a disease, prevention of other risks related to the disease and the desire for herd immunity against an infectious agent push the need for vaccines.
The cost of mass manufacturing of a vaccine must be taken into consideration against the effectiveness of the programme. If the cost is high with poor immunity rates, the vaccine will not be brought to market.
why are vaccines required
New vaccines are required because of recent antibiotic resistance, the threat of new zoonotic pathogens, and because prophylaxis is better than a cure.
how were vaccines developed by Edward Jenner and Louis Pasteur
Edward Jenner variolated his patients. Dried smallpox scabs were introduced to an abrasion of the skin of a boy’s arm. He then contracted a mild form of the disease. Upon recovery, the individual was immune to smallpox (tested by reintroduction). Between 1% to 2% of those variolated died as compared to 30% who died when they contracted the disease naturally.
Louis Pasteur developed weakened (attenuated) strains of Pasteurella after noticing that repeated cultures reduced its pathogenicity.
what is meant by immunity
Immunity is the ability of the human body to protect itself from infectious disease.
what is meant by innate immunity
Innate immunity is non-specific and non-adaptive It is the immunity that is present from birth. It includes:
• Physical barriers (e.g. intact skin and mucous membranes)
• Chemical barriers (e.g. gastric acid, digestive enzymes and bacteriostatic fatty acids of the skin)
• Biological barriers (e.g. phagocytic cells and the complement system)
what is meant by acquired immunity
Acquired immunity is generally specific to a single organism or to a group of closely related organisms. Acquired immunity is developed by active or passive processes.
what is meant by active immunity
Active immunity is protection that is produced by an individual’s own immune system and is usually long-lasting. Such immunity generally involves cellular responses (cell-mediated), humoral responses (antibody-mediated) or a combination acting on the infecting organism. Active immunity can be acquired by natural disease or by vaccination. Vaccines generally provide immunity similar to that provided by the natural infection, but without the risk from the disease or its complications.
describe how cell mediated immunity works
Cell-mediated immunity is controlled by a subset of lymphocytes called T lymphocytes or T cells. T cells mediate three principal functions: help, suppression and cytotoxicity.
• Cytotoxic T cells (CTLs, where CD8+ is the most common) recognise and destroy infected cells by phagocytosis to destroy pathogens.
• T-helper cells (CD4+) stimulate and modulate the immune response of other cells; they activate phagocytic macrophages by cytokines, in particular IFN-, to destroy and engulf bacteria.
describe how antibody-mediated immunity works
Antibody-mediated responses are produced by B lymphocytes (B cells). When a B cell encounters an antigen that it recognises, the B cell is stimulated to proliferate and produce large numbers of lymphocytes secreting an antibody to this antigen. Replication and differentiation of B cells into plasma cells is regulated by contact with the antigen and by interactions with T cells (a type of lymphocyte), macrophages and complement. They provide immunity by:
• Neutralising antibodies (nABs), which block the binding of pathogens to cell-surface receptors, preventing the pathogen from becoming infective
• Antibody dependent cellular cytotoxicity (ADCC), which makes CD8 cells target infected cells
• Opsonising, which involves coating pathogens and targeting them for phagocytosis
• Complement cascade, where the antibody-antigen complexes activate the cascade leads to destruction of pathogen via phagocytosis or bacterial membrane attack.
what are the different roles of the different subtypes of antibodies
IgM is a major antibody in the complement cascade. It is induced by vaccination.
IgG is systemic, found in blood, lymph nodes and tissues. It performs all major roles (nABs, ADCC, Opsonisation & complement cascade). It is induced by vaccination.
IgA is the principle isotope in mucosal secretions in the gastro-intestinal, respiratory & genital tracts. It is a less potent opsonin and a weak activator of complement but is a strong viral neutraliser.
what is passive immunity
Passive immunity is protection provided from the transfer of from immune individuals. Naturally, immunity is passed from mother to child across the placenta (IgG) during the last 10 weeks of pregnancy and from breast milk (secretory IgA). This protects against lung and GI infections; bottle-fed babies are 60x more likely to develop pneumonia in first 3 months of life compared to breast-fed babies. However, protection provided by the cross-placental transfer of antibodies from mother to child is more effective against some infections (e.g. tetanus and measles) than for others (e.g. polio and whooping cough). This protection is temporary, lasting for only a few weeks or months.
Passive immunity can be caused by transfusion of blood or blood products including immunoglobulin.
how do vaccines produce their protective effect
Vaccines produce their protective effect by inducing active acquired immunity and providing immunological memory; memory cells allow the immune system to recognise and respond rapidly to re-infection, which higher antibody concentrations.
For a vaccine to be effective, it must trigger the proliferation of naïve t-cells. Success depends on whether CD4+ Th1 and CD8+ responses are induced (intracellular organisms) or CD4+ Th2 responses are induced (extracelullar organisms).
how to naive T cells work to produce their protective effects
• Naïve T-cells proliferate in response to an antigen, forming effector cells (which deal with the present infective agent) and memory cells (which remember the infective agent so upon re-infection, the immune system can respond very quickly and potently to destroy it)
how do naive B cells work to produce their protective effect
• Naïve B-cells proliferate in response to an antigen, forming plasma cells (which deal with the present infective agent) and memory cells (which remember the infective agent so upon re-infection, the immune system can respond very quickly and potently to destroy it).
explain how paediatric immunity works
Babies are at their most vulnerable for the first 28 days of their life. Although antibody synthesis begins in foetus at 20 weeks, infants are reliant on maternal ABs for the first 2 months. Because of this, children under 8 weeks cannot be vaccinated. After 8 weeks, they can be vaccinated. However, their adaptive immune system is immature (T-cells are all naïve but do not respond to antigens) and attenuated viruses pose the risk of virulence. As a consequence, toxoids, glycoconjugates and recombinant protein vaccines can be used, with aluminium-based adjuvants. These are weakly immunogenic and require booster immunisations.
when was the first paediatric vaccine given
The first paediatric vaccines are given at 2 months because maternal antibodies begin waning. The inactivated components of the Infanrix vaccine are safe to use, and there is a high risk of infection from pathogens contained in the vaccine. There is also a high risk of infection of Men B & Rotavirus. PCV conjugate vaccine is given because the immature immune system cannot process polysaccharide-only vaccines. Boosters are given at 12 & 16 weeks, to ensure immunity. Side effects of the Infanrix vaccine include dermatitis, restlessness, crying and disturbed sleep; the Rotarix vaccine may cause vomiting/ diarrhoea.
At 1-year, thymic T cells develop. These cope with attenuated vaccine, unless there is a malignancy/ disease where the the immune system is compromised. The MMR vaccine is given at 1-year, and the flu vaccine is given at 2-years. By age 5, the immune system is fully developed. The MMR vaccine may cause malaise (general discomfort), fever or rash.
describe how elders immunity works
T-cells stop living after about 40 divisions due to the short length of telomeres. B-cell clones can outgrow and become malignant. T & B cell senesce results in more infections, especially respiratory tract infections. The elderly may contract shingles due to latent chickenpox virus (varicella zoster); this is a sign of secondary immunodeficiency due to malignant B-cells.
what characteristics must a vaccine have
Vaccines must be safe, with low toxicity. They must offer effective protection against infective agent to rapidly generate herd immunity and ideally, produce long-lived immunity to reduce the amount of booster doses required; this reduces the cost involved and complexity of vaccine regimens. They should be cheap, or cost-effective, as they will be administered widely.
They should contain only purified components (i.e. the key antigens only): for intracellular organisms, CTL and Abs are needed, for extracellular organisms, only Abs are needed. They should target specific epitopes (the part of an antigen molecule to which an antibody attaches itself), as some epitopes do not generate protective Abs/ CTLs and may cause adverse side effects.
Stimulation of mucosal immunity may be required to provide defence at the point of entry. They may have to include pre-existing antibodies to form the antigen-antibody complex which is phagocytosed (e.g. diphtheria & tetanus endotoxins) or block viral-ligand cell receptor interaction (e.g. Polio & HIV).
what are the different types of vaccines
• Monovalent vaccines offer immunity against a single antigen/strain of a pathogenic microorganism (e.g. Rotavix).
• Multivalent vaccines offer immunity against multiple strains of a pathogenic microorganism (e.g. Men ACWY).
• Combination vaccines offer immunity against multiple pathogenic microorganisms (e.g. Infanrix hexa 6-in-1).
• Heterologous vaccines offer immunity against a pathogen that shares cross-reacting antigens with the microorganism present in the vaccine (e.g. small-pox vaccinia).
Homotypic vaccines contain one component.
• Heterotypic vaccines contain many components; this may be a modified whole cell, a toxoid.
what viral and bacterial infections do live vaccine target
viral: MMR
Influenza
Rotavirus
Polio
bacterial
Mycobacterium tuberculosis (BCG)
Salmonella typhi
what viral and bacterial infections does attenuated (killed) vaccines target
viral: Influenza
Polio (IPV)
bacterial: Corynebacterium diphtheriae Clostridium tetani Haemophilus influenzae type b Bordetella pertussis Rickettsia spp. (typhus) Streptococcus pneumoniae
what viral and bacterial infections does purified protein and toxoids vaccines target
viral:Palivizumab is a monoclonal antibody that recognises Respiratory Syncytial Virus (RSV)
bacterial: Corynebacterium diphtheriae (toxoid) Clostridium tetani (toxoid) Neisseria meningitidis (group B)
what viral and bacterial infections does recombinant protein vaccines target
viral : Hepatitis B
bacterials: Neisseria meningitidis (group B)
what virus infections does the virus like vaccine target
HPV
what bacterial infection does the polysaccharide vaccine target
Neisseria meningitidis
Haemophilus influenzae
Streptococcus pneumoniae
(NHS)
what bacterial infection does the Glycoconjugate vaccine target
Neisseria meningitidis (groups A, C, W, Y)
what is a live (attenuated) vaccine
Attenuation is the process of losing the virulence of a pathogenic organism. Previously, the organism was attenuated via repeated passage in cells or chick embryos. Now, attenuation is achieved via mutation of a specific genes in non-human cells; the virus is isolated & grown in human cultured cells, then used to infect monkey cells. The virus acquires many mutations that enable proliferation in monkey cells, but it no longer grows well in human cells, so can be used as a vaccine. If the antigen responsible for inducing protective immunity is known, genetic manipulation allows the creation of a safe, potent vaccine. To attenuate, only 10 genomes need to be changed; this prevents virulence but give immune response. Live vaccines require cold chain (refrigeration). Attenuated vaccines are only used in those with mature immune system (aged 2-65 and non-immunosuppressed. Attenuated vaccines generally give a better immune response because it triggers both types of immunity, producing Abs & CTLs, and also gives mucosal immunity.
e.g. Oral polio vaccine (OPV) – oral drop offers lifelong immunity. In addition, the vaccine is shed in faeces, so in areas where faecal contamination is prevalent, it may offer mass immunisation.
what is a killed vaccine
Virus/bacteria grown in culture and the organism can be inactivated physically (heat, radiation) or chemically (formalin). It must be tested for inactivation before use. If vaccine only contains killed microorganisms, no cold chain is required. Therefore, killed vaccines are better in less-developed countries, or hard-to-reach regions. They can be used in children, elderly & immunosuppressed. However, a limitation is that only Abs are produced; no CTLs and no mucosal immunity is produced, so multi-doses are needed (priming, boosting at specific intervals).
e.g. Inactivated poliovirus vaccine (IPV) – two injections protects 90% of the population; three injections protects 99% of the population at $25-50 per person.
what is a purified protein vaccine
Pathogenic organisms may emit a toxin, which induce powerful Th2-type response (ABs). The toxin can be chemically inactivated using formalin to become toxoid, which is active as a vaccine. Immunisation with toxoids creates memory B-cells which produce nABs upon reinfection, where they bind to and complex the bacterial toxins, inactivating them.
e.g. Humanised IgG mAB, Palivizumab is used to treat severe paediatric Respiratory Syncytial Virus (RSV) infection by passive immunisation; it binds to fusion protein on RSV, preventing the virus from binding to surface receptors on target cells.
what is a recombinant vaccine
Subunit vaccines contain only specific antigens/ epitopes that induce potent & specific protective immune responses. Adverse reactions are rare, the contain specific antigens/epitopes induce protection. Once the key antigens/epitopes identified, subunit vaccines can be manufactured:
- Chemical fractionation of microbe
a. purification and stabilisation of key antigens
b. chemical linkage of antigens (if needed) - If key epitopes are known
a. Manufacture as peptides, that link amino acids in specific sequence
b. Three-dimensional epitopes are created using “Scaffolds” - Recombinant DNA technology
a. Genetic construct coding for antigens/polyepitopes
b. Expression as soluble proteins/ glycoproteins
e. g. the gene responsible for Hepatitis B’s Surface Antigen is isolated and introduced into yeast, where it is modified and may be expressed as pure HBsAg.
e. g. pertussis – four protective antigens (pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN) and fimbrial antigens were isolated and incorporated into Infanrix vaccine, replacing the whole-cell vaccine. It was as effective, few/ no side effects.
what is a virus like particle vaccine
The particles self-assemble and form a structure similar to the virus, which is recognised by APCs. e.g. Gardisil
what is a polysaccharide vaccine
Encapsulated bacteria (see table) have a slimy layer composed of polysaccharides. This polysaccharide capsule is antigenic, producing an immune response independent of T-cells. It is useful in adults, but provides little protective immunity in children, because they cannot produce a T-cell-independent immune response or lay down memory cells. e.g. Pneumovax 23
what is a Glycoconjugate vaccine
Since polysaccharide vaccines are not effective in children, modification of antigens is needed: Chemically-coupling of the polysaccharide capsular antigens (PS) to a carrier protein (e.g. toxoid from tetanus/ diphtheria). e.g. Men ACWY
what are effective deliveries of injections based on
Effective delivery is based on the following notions:
• efficient encapsulation (trapping) of the active
• successful ‘targeting’ of the active to a ‘specific’ region of the body & pathogen
• successful release of that active in situ
how is vaccines given via IM
Most vaccines are given via IM injection; however, this is impractical in a number of ways. Firstly, it is painful and therefore unpopular, reducing the uptake. Needles/ syringes are expensive, so the cost is driven up, and it is laborious for mass immunisation. Since most pathogens enter via the mucosa, the immune response may not be optimally stimulated.
how is oral/nasal vaccines given
Delivery is easier for patient and professional, with fewer delivery-related side effects. Polio eradication campaign success due to simplicity of OPV. Paediatric flu vaccine is given intranasally.
