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vaccinology overview - Coggle Diagram

- - - - each dose of vaccine protects many more individuals than the vaccine recipient
  - - - one solution to this is the provision of booster doses of vaccine through childhood in an attempt to sustain antibody levels above the protective threshold
    - - lifelong protection following a single dose is possible in some live attenuated viral vaccines although some provide incomplete infection
      - sometimes immunity wanes or initial vaccination does not induce a successful protective immune response
    - - phenomenon describes how the immune system fails to generate an immune response against a strain of a pathogen if the host was previously exposed to a closely related strain
      - might have important implications for vaccine development if only a single pathogen strain or pathogen antigen is included in a vaccine
        
        vaccine recipients might then have impaired immune responses if later exposed to different strains of the same pathogen, potentially putting them at increased risk of infection or more severe disease
      - strategies to overcome this include the use of adjuvants that stimulate innate immune responses which can induce sufficiently cross-reactive B cells and T cells that recognise different strains of the same pathogen, or the inclusion of as many strains in a vaccine as possible
        
        latter approach is limited by the potential of new strains to emerge in the future
  - - - some individuals are not vaccinated for various reasons
      - others do not mount an immune response despite vaccination
  - - - epigenetic changes
        
        can occur in innate immune cells as a result of vaccination
        
        remains unclear how current immunisation schedules might be adapted to improve population protection through non-specific effects
- - - - total IgG antibody levels against pneumococci
        
        contain mechanistic correlation (thought to be a subset of opsonophagocytic antibodies) but mechanism of protection is not being directly measured
- - - - fever
      - malaise
      - headache
- - - - polysaccharide antigens can also induce protective immune responses (basis of vaccines that have been developed to prevent bacterial infections such streptococcus pneumonia)
    - - prevention of infection
      - reduction in disease severity
      - decreased rate of hospitalization
  - - - may have potential to replicate in an uncontrolled manner in immunocompromised individuals (children with primary immundeficiencies, individuals with HIV infection, those on immunosuppressive drugs)
        
        thus some restrictions
      - developed so that in an immunocompetent host they replicate sufficiently to produce a strong immune response, but not so much as to cause significant disease manifestations
        
        MMR
        
        oral polio
        
        BCG vaccine for TB
        
        live-attenuated influenza
      - trade off between enough replication of the vaccine pathogen to induce a strong immune response and sufficient attenuation of the pathogen to avoid symptomatic disease
        
        some require multiple doses and induce relatively short-lived immunity
        
        others may induce some mild disease
    - - pose no risk to immunocompromised individuals
      - may not confer protection in those with B cell/combined immunodeficiency
      - antigenic component of non-live vaccines
        
        killed whole organisms
        
        purified proteins from the organism
        
        recombinant proteins
        
        polysaccharides
      - toxoid vaccines are formaldehyde-inactivated protein toxins that have been purified from the pathogen
      - often combined with an adjuvant to improve their ability to induce an immune response (immunogenicity)
        
        only a few used routinely in licensed vaccines
        
        portfolio is steadily expanding
        
        liposome-based adjuvants
        
        oil in water emulsions
        
        some influenza vaccines
        
        mechanism of action of aluminium salts (alum), although extensively used as an adjuvant for 80+ years remains incompletely understood
        
        increasing evidence that immune responses and protection can be enhanced by the addition of newer adjuvants that provide danger signals to the innate immune system
    - - viral vectors
      - nucleic acid-based RNA and DNA vaccines
      - virus-like particles
  - - - antibiotics
      - egg/yeast proteins
      - latex
      - formaldehyde
      - gluteraldehyde
      - acidity regulators
        
        potassium
        
        sodium salts
      - except in the case of ALLERGY there is NO EVIDENCE of risk to human health from these trace components of some vaccines
- - - - immunodeficiency states
        
        individuals with some known immunological defects in antibodies or associated immune components are particularly susceptible to infection with certain pathogens
        
        can provide insight into the characteristics of the antibodies that are required for protection from that particular pathogen
        
        deficiencies in the complement system are particularly susceptible to meningococcal disease caused by infection with Neisseria meningitidis
        
        control of this infection depends on complement-mediated killing of bacteria whereby complement is directed to the bacterial surface by IgG antibodies
        
        some antibody deficient individuals are more susceptible to eg. varicella zoster virus (chickenpox) but once infected can control the disease in the same way as an immunocompetent individual so long as they have a normal T cell response
      - studies of passive protection
        
        intramuscular or intravenous infusion of exogenous antibodies can provide protection against some infections
        
        eg. maternal antibodies across the placenta which provides newborn infants with protection against a wide variety of pathogens for several months after birth
        
        maternal vaccination harness this important protective adaptation to reduce risk of disease soon after birth and clearly demonstrates the role of antibodies in protection against these diseases
        
        use of specific neutralising antibodies purified from immune donors to prevent the transmission of various viruses
        
        individuals with inherited antibody deficiency are without defence against serious viral and bacterial infections
        
        regular administration of serum antibodies from an immunocompetent donor can provide almost entirely normal immune protection for the antibody-deficient individuals
      - immunological data
        
        increasing knowledge of immunology provides insights into the mechanisms of protection mediated by vaccines
        
        polysaccharide vaccines made from surface polysaccharides of invasive bacteria provide considerable protection against relevant disesases
        
        do not induce T cell responses as polysaccharides are T cell independent antigens and thus they must mediate protection through antibody-dependent mechanisms
        
        protein polysaccharide conjugate vaccines contain the same polysaccharides from the bacterial surface
        
        chemically conjugated to a protein carrier (mostly tetanus or diphtheria toxoid or a mutant protein derived from it)
        
        T cells induced by the vaccine recognise the protein carrier (a T cell dependent antigen) and these T cells provide help to the b cells that recognise the polysaccharide
        
        no T cells are induced that recognise the polysaccharide and thus only antibody is involved in the excellent protection induced by these vaccines
        
        human challenge studies offer the opportunity to efficiently assess correlates of protection under controlled circumstances and have been used to demonstrate role of antibodies in protection against malaria and typhoid
- - - - cytotoxic
        
        required to control and clear established infection
      - helper
        
        subtypes of helper can be distinguished by profiles of cytokine production
        
        helper 1 and 2 are mainly important for establishing cellular immunity and humorla immunity respectively
        
        Th1 cells also associated with generation of the IgG antibody subclasses IgG1 and IgG3
        
        other subtypes include Th17 cells which are important for immunity at mucosal surfaces such as the gut and lung
        
        t follicular helper cells located in secondary lymphoid organs
- - - - for most vaccines used in the first year of life 3-4 doses are administered by 12 months
      - conventionally PRIMING doses are all those administered <6mo and boosters are 9-12mo
      - schedule selected to provide early protection before levels of maternal antibody waned and vaccine compliance is also better when doses are given close together
      - infant immunisation schedules around the world ae highly variable
    - - established during early clinical development
        
        optimal safety
        
        immunogenicity
      - for some populations a higher dose may be beneficial (eg. older adults)
    - - highest burden of and mortality from infectious disease occur in the first 5 years of life
      - immunisation programmes largely focus on <5 age group - greatest benefit from vaccine-induced protection
        
        makes sense epidemiologically
        
        somewhat inconvenient from an immunological perspective as the induction of strong immune responses in the first year of life is challenging
        
        interference from maternal antibody might reduce antigen availability, viral replication or regulate B cell responses
        
        bone marrow niches to support b cells are limited in infancy which might explain short lived immune esponses
        
        physiological age-dependent increase in antibody responses in infancy
        
        T cell dependent antigens
        
        plain polysaccharides from Hip, typhoid causing bacteria, meningococci and pneumococci
        
        antibody responses depend on development of the marginal zone of the spleen which is required for the maturation of marginal zone B cells, which does not occur until around 18 months of age in human infants
        
        these plain polysaccharide vaccines do not induce memory B cells and even in adults provide protection for just 2-3 years
        
        protection results from antibody produced by plasma cells derived from marginal zone B cells
        
        converting plain polysaccharide vaccins into T cell dependent protein polysaccharide conjugate vaccines (immunogenic from 2 months of age and induce immune memory) has transformed prevention of disease caused by the encapsulated bacteria
      - vaccination of older children and adults induces strong immune responses but are of little value if those who would have benefited from vaccination have already succumbed to the disease
      - immune responses are also poor in older population
        
        most vaccines used in older adults offer limited protection or a limited duration of protection, particularly among those older than 75 years of age