Vaccinations 9/12 Flashcards
Purpose of Vaccines
- prevention of disease in an individual and a population
- provides an individual with the primary immune response to a pathogen
- vaccines are effective if infectious agent does not establish latency, if it does not undergo much antigenic variation, and if it does not interfere with the host immune response
- vaccines are most effective against infections that are limited to human hosts, without animal resevoirs
- herd immunity: the sufficient number of immune individuals in a population to prevent transmission of infection
- if organism is highly infectious - need a higher proportion of the population to be immune to maintain herd immunity
Passive immunization
- immediate immunity, but is transient
(1) prevent disease after a known exposure
(2) ameliorate symptoms of an ongoing disease
(3) protect immunosuppressed patients
(4) block action of bacterial toxins and prevent
diseases that they cause.
Examples:
(a) snake bite antivenom
(b) passive transfer of Ig from mother to child
Active Immunization
- delayed immunity, but more permanent
Examples :
(1) natural exposure to pathogens
(2) vaccines
combined passive/active immunity
Designed to give both immediate, transient protection as well as slowly developing durable protection
Examples: Tetanus, Rabies
How to make vaccines…
Vaccines are defined as whole or parts of microorganisms administered to prevent an infectious disease.
The first step in making a vaccine is to separate two effects of disease causing organisms.
What does this mean? Isolating or creating an organism, or part of one, that is: unable to cause full blown disease but still retains the antigens responsible for inducing host immune responses.
Vaccine characteristics:
- must evoke protective levels of immunity at appropriate site
- must be readily cultured in bulk
- must be stable under extreme climatic conditions - preferably not requiring refrigeration
- should be accessible to third world
- should eliminate any pathogenicity
characteristics of Vaccines
Site at which the pathogen enters the body.
Infection via mucosal surfaces of the respiratory tract and gastro-intestinal tract. IgA
- Examples: rhinoviruses; myxoviruses; coronaviruses; parainfluenzaviruses; respiratory syncytial viruses; rotaviruses (stay in GI/ respiratory tract)
Infection via mucosal surfaces followed by spread systemically via the blood and/or neurones to target organs. - needs to be IgA
- Examples: picornaviruses; measles; mumps; HHVs; hepatitis A & B
Infection via needles or insect bites, followed by spread to target organs: - periphery = IgG
- Examples: hepatitis B; alphaviruses; flaviviruses; bunyaviruses
Also need to know:
Viral antigen(s) or cell surface antigen(s) that elicit
neutralizing antibody
The site of replication of the pathogen
4 types of vaccines: killed organism, acellular, attenuated, toxoid, mimic, subunit, DNA plasmid
(1) Killed organism: inactivated or killed microorganism
* Example : Salk polio vaccine
(2) Acellular: uses antigenic part of disease causing organism
* Example: DTaP (acellular pertusis)
(3) Attenuated: can be attenuated by environmental conditions or genetic engineering. An attenuated vaccine is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable (or “live”).
* Example: MMR (using actual pathogen, but then mutating it so that it cannot cause pathogenicicty)
(4) Toxoid: toxins treated with or absorbed with aluminum salts
* Example: Tetanus toxoid
A toxoid is a bacterial toxin (usually an exotoxin) whose toxicity has been inactivated or suppressed either by chemical (formalin) or heat treatment, while other properties, typically immunogenicity, are maintained.
(5) Mimic: use organism similar to virulent organism but that does not cause human disease
* Examples: Vaccinia (causes same disease in cows), BCG for M. tuberculosis
(6) Subunit: utilizes techniques of genetic engineering. Adjuvants needed for immune response.
* Examples: Hep B, HIB, N. meningitidis
(8) DNA plasdmid: circular DNA plasmids expressing specific proteins are injected with presentation of the protein to the immune system; hypothesis is that it mimics a live attenuated vaccine preparation.
* Examples: HIV in development, Vaccinia vector
Thimersol
- Thimerosal was one of the most widely used preservatives in vaccines.
- It is metabolized or degraded to ethylmercury and thiosalicylate in vivo.
- Ethylmercury is an organomercurial that is metabolized differently than methylmercury.
- Methylmercury is a neurotoxin.
Currently, all US pediatric vaccines in the routine infant immunization schedule are manufactured in single-dose packaging that does not require a preservative.
Adjuvants
- help bring the Ag into contact with the immune system and influence the type of immmunity - help keep Ag in the proper area so immune system can recognize it
- decrease the toxicity of certain Ags
- provide solubility to some vaccine components
- Inorganic Salt - Aluminum hydroxide (alhydrogel), only FDA approved adjuvant
- To work as an adjuvant, the antigen must be clumped with the aluminum salt to keep the antigen at the injection site.
Immunization shcedule for children
Considerations
1. Timing of likely exposure
2. Immunological maturity of the child
3. Passively transferred antibodies may
interfere and bind Ags injecting with vaccine, not allowing for immunization to occur
4. “Boosters” for immunological priming
Simultaneous administration of a vaccines is necessary to reduce the number of visits as much as possible.
Administration, timing, dosing
Parenteral Route: Elicits IgG
- Subcutaneous
- Intramuscular (adjuvants)
- Intradermal
Oral Route: Elicits IgA
Exposure/ Previous Infection:
- Vaccination of infants and children against agents that cause severe consequences during infancy and early childhood.
Dosing:
- Immunogenicity without pathogenicity
contraindications to immunization
- Acute febrile illness
- Immunosuppressive therapy e.g. steroids, alkalating agents, irradiation
- Recent administration of whole blood, plasma or immune serum globulin
- Simultaneous administration of another live vaccine unless shown to be effective
- Immunodeficiency states: humoral /cellular
- Pregnancy (live viral vaccines contraindicated)
- Leukaemia and Lymphoma, some other malignancies
Potential problems with vaccines:
- Clinically important epitopes may not be intact in vaccine
- Individual genetics may effect efficacy
- Some individuals may be genetically
- predisposed to adverse events
- Often work poorly in very young infants or the elderly
- Many do not induce CMI; Ab may not be sufficient
– no vaccine is totally safe
Effective vaccines may produce undesirable side effects which are mostly mild and clear up quickly. These are caused by a number of different mechanisms.
- Inflammatory responses (you want these)
- Conversion to wild-type (attenuated vaccines) – however, the attenuated process renders them less pathogenic
- Allergic reactions
Future of Vaccines
Sequential Immunization: DNA vaccine followed by pox expressing antigen
Sequencing of genes of pathogens for appropriate antigenic epitope sequences
Vaccination against cancer: Prevention of Hepatitis B (Taiwan –70% reduction in hepatocellular cancer following vaccination) or Papillomaviruses (HPV)
Alzheimer`s disease: Amyloid B peptide vaccine and immunotherapy
Challenges for Vaccine devleopment
- Different types of pathogens may cause similar diseases – e.g. the common cold. As a result, a single vaccine will not be possible against such a disease.
- Antigenic drift and shift: This is especially true of RNA viruses and those with segmented genomes.
- Large animal reservoirs. Re-infection after elimination from the human population may occur.
- Integration of viral DNA. Vaccines will not work on latent virions unless they express antigens on cell surface. In addition, if the vaccine virus integrates into host cell chromosomes, it may cause problems.
- Transmission from cell to cell via syncytia - This is a problem for potential HIV vaccines since the virus may spread from cell to cell without the virus entering the circulation.
- Recombination and mutation of the vaccine virus in an attenuated vaccine.
