VACCINES!!!! Flashcards
Immunization
process by which a person or animal becomes protected against a disease
often interchangeable with vaccination or inoculation
How is it that smallpox was eradicated?
Humans are the only host
were able to identify a vaccine target
effective vaccine
virus is stable
Vaccine
product that produces immunity therefore protecting the body from the disease
Active immunization
directed at a specific organism
injection of killed, weakened or subunit of an infectious organism in order to elicit an immune response which is effective at preventing the disease when encountered
Passive immunization
alternative to vaccination for those already infected or are immunodeficient
may be acquired naturally (breatmilk) or artifically (Ab containing preparation)
Two types of Ab preparations are available
- normal human immunoglobin (pooled sera)
- specific hyper immune human immunoglobin
- preformed antibodies taken from an individual (s) during convalescence or following vaccination
what are requirements for a successful vaccine?
safety
induction of protective immune response (effectiveness, proper cell responses must be evoked)
Practical issues - affordable, stable, administration, perception
Vaccine efficacy is related to
duration of immunity elicited
Traveler’s vaccines last
a short period
months to years for Cholera
Two years for TAB vaccine - typhoid/parathypoid
DTap vaccine
lasts 3 to 5 years
BCG vaccine
5 or more years
Vaccines that last about ten years
Tetanus (Td) yellow fever
Vaccines with solid immunity/lifetime
MMR - measles, mumps and rubella
What are efficacies of some vaccines given?
Absolutely protective - 100% - yellow fever vaccine
almost abs. protective - Variola, measles, mumps, rubella, diphtheria and tetanus
highly protective - (80-95%) - polio, BC, Hep B, and pertussis
Moderately protective - (40-60%) - TAB, cholera vaccine, and influenza
Herd immunity
acts as firewall to block or slow disease transmission
since some vaccines do not cover 100% of people, some people given the vaccine will remain unprotected
some people are not able to receive vaccines - the immunocompromised - so this is most effective way to protect these ppl
for non infectious diseases - there is no herd immunity
Additives used in production of vaccines may include
suspending fluid - sterile water, saline, or fluids containing proteins
Preservatives and stabilizers - helps it remain potent and unchanged - albumin, phenols, glycine
adjuvants or enhancers to help the vaccine to be more effective
Some common ingredients in vaccines
aluminum gels or salts - adjuvant
antibiotics - no vaccine in the US has penicilllin
Albumin - egg protein in influenza and yellow fever vaccines
Formaldehyde - to inactivate bacterial products for toxoid vaccines (most is removed before packaging)
Monosodium glutamate and 2-phenoxy-ethanol - stabilizers in a few vaccines, help vaccine remain unchanged when exposed to heat, light, acidity or humidity
thimersol - mercury containing preservative, in vials of vaccine that contain more than one dose to prevent contamination, All US vaccines are available with no or trace amounts of thimersol
Types of vaccines
Live attenuated vaccines
Non living whole organisms vaccines
Non-living subcellular fragment vaccines
Passive immunization
Live attenuated vaccines
microbes with artificially reduced virulence
microbes with naturally reduced virulence for humans
Non-living whole organism vaccines
inactivated/killed whole organism
Non-living subcellular fragment vaccines
toxoid - inactivated toxin
recombinant vecor expressing protein of interest
surface antigen alone - peptide or capsular polysaccharide
Conjugate vaccines
In live attenuated vaccines where the microbe has artifically reduced virulence usually
do not cause serious disease in healthy ppl
Genetic roulette
randomly mutated by imposing unusual growth conditions
low temp, abnormal host cell, and select for loss of virulence with continued antigenicity
Measles, mumps, rubella, influenza, VZV, polio (sabin), yellow fever, BCG
site directed mutations and deliberate deletions of virulence genes
Microbes with naturally reduced virulence for humans
pathogen from related species can be used to elicit protective response
vaccinia virus for smallpox
rotavirus vaccine - reassortant virus with gene segments from human and animal rotaviruses or an attenuated human rotavirus
Advantages of live attenuated vaccines
elicit a better memory response than killed vaccines, therefore, provide longer-lasting immunity
- replication competent (to an extent)
- localize to site where protection is required - OPV (sabin) vaccine induces gut immunity (IgA) vs. IPV (Salk) inducing IgG (IM)
Disadvantages of Live attenuated vaccines
instability if cold chain not maintained
potential for reversion to wild-type and production of disease
small probability of causing serious disease in IC/immunodeficient pts
-OPV (Sabin) vaccine
-Smallpox vaccine in person with eczema (immunodeficient) or HIV pt
Attenuation
the process of weakening a pathogen
- serial passage in cells cultured in vitro (OPV)
- adaptation to low temperature (intranasal influenza vaccine)
What is serial passage?
pathogenic virus is isolated from a pt and grown in human cultured cells then cultured virus is used to infect monkey cells then virus acquires many mutations that allow it to grow well in monkey cells
Lastly, the virus no longer grows well in human cells amd may be a candidate for a vaccine
Induced immune response from Live attenuated vaccines
virtually identical to that produced by natural infection - leads to more robust immune response overall
Humoral immunity - Ab responses to surface proteins
Cell mediated immunity - CD4 and CD8 responses
Characteristics of non living whole organism vaccines (killed or inactivated)
used where live vaccines are not available
could be because attentuation was not achieved or reversion to wild type occurs too easily
it loses the capacity to replicate in the host but maintains the antigenic properties of some of its components - Rabies, IPV (salk), Hep A
Advantages of Killed/non living whole organism vaccines
non infective, therefore relatively safe
Disadvantage of non living, whole organisms vaccines
lower immunogenicity therefore needs several doses (prime boost)
Inactivation methods
Beta-propiolactone (rabies, influenza)
Formaldehyde/formalin (polio-salk, Hep A, Yersinia pestis)
Heat (vibrio cholerae)
Heat plus phenol or acetome (salmonella typhi)
Heat or formaldehyde (bordetella pertussis)
Colicin (E. coli) - endonuclease that destroys chromosomal and plasmid DNA, leaving intact cells with a normal complement of antigens
UV irradiation
Gamma irradiation
Examples of non living subcellular fragment vaccines
acellular pertussis vaccine (aP)
Influenza vaccine
Polysaccharide capsules of pneumococci, haemo. and meningococci
surface coat of hep B, which is produced by recombinant DNA tech
fragmented virus or purified surface antigens of influenza virus
protein filaments (pili) used by E. Coli and Neisseria gono. to attach to urinary tract epithelium (still experimental)
Tetanospasmin
Toxoid vaccine
inactivated bacterial toxins that induce neutralizing antibody
toxin in activated and used to immunize
DTP
Diphtheria, tetanus in combination with killed Bordetella pertussis
(diphtheria, tetanus, pertussis)
Omission of pertussis component reduces the antibody response to the two toxoids
thus pertussis acts as an adjuvant as well as vaccine
Recombinant vector vaccine
a variety of viruses and bacteria can be used as vectors for cloned genes (genetic engineering)
Expression vector, complete with inserted gene(s), is itself the vaccine
Following injection, it will proliferate sufficiently to release an immunizing amount of foreign protein, but without inducing disease itself
Successful recombinant vaccines
Hep B, respiratory syncytial virus, EBV, rabies virus, dengue virus and lassa fever virus
HPV vaccine includes virus like particle
single viral protein isolated/strain of virus
2 vaccines available provide protection vs. 2 or 4 strains of HPV
when proteins are expressed, virus-like particles (VLPs) are created
contain no genetic material from the viruses
Expression vector vaccine examples
attenuated yellow fever virus, adenovirus, HSV, VZV, VacV, attenuated salmonellae, BCG, S. Typhi
Polysaccharide and polypeptide (cellular faction or recombinant) vaccine
prepared from extracted cellular fractions
prepped using recombinant technology
Their efficacy and safety appear to be high
Example of polysaccharide and polypeptide vaccine
Hepatitis B polypeptide vaccine - HbS Ag
Example of recombinant vaccine
Influenza (shot) with HA and NA surface antigen proteins as immunogens
Method for enhancing immunogenicity of inactivated and subunit vaccines?
Addition of an adjuvant
Adjuvant
substance that enhances T cell activation by promoting accumulation of APCs at site of antigen exposure and enhancing co-stimulator and cytokine expression by the APCs
Examples of Adjuvants
Aluminum: aluminum hydroxide, aluminum phosphate
Alum: potassium salts
Mixed aluminum salts
ASO4 (is it supposed to be AlSO4?), a mixture of alum and a bacterial lipid molecule (cervarix)
Benefits of adjuvants
prolongation of antigen release
activation of macrophages
mitogenicity on lymphocytes
Reduces the amount of the active component required in a vaccine
leads to stronger, more sustained immune response, therefore, fewer doses needed
Elderly, young and IC require an extra boost to provide protection and adjuvant gives this
Mice were given antigen in saline or in Freuds incomplete adjuvant. Which had a greater response? why?
Antigen in freuds incomplete adjuvant elicited a greater response.
Freud’s adjuvant contains fragment of TB, this helps to elicit a strong and more sustained immune response
Conjugate vaccine
made using combination of two different bacterial components
bacterial coats chemically linked to a carrier protein
used to increase antigenicity
Ex. pneumococcal bacterial vaccination
Tetanus or diphtheria toxoids as a ‘carrier’ protein
most ppl have been immunized and posses tetanus-specific memory T cells which will help the peptide-specific B cells make antibody
useful for inducing a good primary response
not effective for establishing memory response, where T cells need to be recalled by the proteins of the infection rather than by those of tetanus
example of Toxoid conjugate vaccine
cholera toxin B subunit in combination with killed organisms
licensed in europe as an oral vaccine
protects for 4-6 months (effective in about 61-86% of people)
safety Problems with Live attenuated vaccines
insufficient attenutation reversion to wild type administration to immunodeficient patient persistent infection contamination by other viruses fetal damage
safety issues with Killed/inactivated vaccines
contamination by toxins or chemicals
allergic reactions
autoimmunity
Safety of vaccine component - Aluminum
implicated as a cause of brain damage suspected factor Alzheimer's disease dementia seizures and coma allergic rxns can occur on skin
Vaccine safety: Formaldehyde (formalin)
poisonous if ingested
probable carcinogen
suspected GI, liver, immune system, nerve, reproductive system and respiratory poison
linked to leukemia, brain, colon, and lymphatic cancer
Vaccine safety: Thimerosal
autism scare but debunked
since 2001, with exception of some influenza vaccines, is not used as a preservative in routinely recommended childhood vaccines
For vaccine development FDA sets rules for the 3 phases. Always tested on adults first Phase 1
20-100 volunteers is this vaccine safe? does this vaccine seem to work? are there any side effects? How is the size of the dose related to side effects?
Phase 2 of vaccine development
several hundred volunteers
what are the most common short term side effects?
how are the volunteers immune system responding to the vaccine?
Phase 3 of vaccine development
Hundreds or thousands of volunteers how do ppl who get the vaccine and ppl who do not get the vaccine compare? is the vaccine safe? is the vaccine effective? what are the most common side effects?
FDA licenses vaccines only if
its safe and effective
benefits outweigh the risks
ACIP or advisory committee on immunization practices
group of medical and public health experts
members of american academy of pediatrics (AAP) and american academy of family physicians (AAFP) are among some of the groups that also bring related immunization expertise to the committee
develop recommendations for vaccine use
ACIP recommendations are not official until
the CDC director reviews and approves them and they are published
these recommendations then become part of the US official childhood immunization schedule
VAERS - Vaccine Adverse event reporting system
collects and analyzes reports of adverse events that happen after vaccination
anyone can submit a report, including parents, patients and healthcare professionals
Vaccine safety datalink
network of healthcare organizations across of the US
healthcare information available of over 9 million ppl
scientists use VSD to conduct studies to evaluate the safety of vaccines and determine if possible side effects are actually associated with vaccination
Vaccine preventable diseases on the US required vaccine schedule
DTaP or TDaP Hep A and B H. Inf - Hib Influenza - seasonal flu MMR Meningococcal Pneumococcal Polio Rotavirus Varicella
FYI additional vaccine preventable diseases
Anthrax Cervical cancer HPV H1N1 flu Japanese Encephalitis Lyme disease Monkey pox Rabies Shingles Smallpox TB Typhoid fever Yellow fever
Examples of Live, attenuated vaccines
MMR
varicella
Influenza (nasal spray)
Rotavirus
Examples of inactivated/killed vaccines
Polio (IPV)
Hep A
examples of Toxoid (inactivated toxin)
DTaP
Examples of subunit/conjugate vaccines
Hep B Influenza (injection) Hib Pertussis (in DTaP) Pneumococcal Meningococcal
