Vaccines Flashcards
What vaccines does the CDC recommend to children to get?
- MMR- measles, mumps, rubella (german measles)
- varicella (chickenpox)
- Hepatitis B
- DTaP- diptheria, tetanus, pertussis (whooping cough)
- Haemophilus influenza type B (Hib)
- polio (IPV)
- influenza (flu)
- pneumococcal polysaccharide disease
- Human papilloma virus
- rotavirus
- Hepatitis A
- Meningococcal B
What was one of the first vaccines? live natural viral vaccines? (9)
- used material from dried pustules of people who got mild smallpox
- variolation:
- widely used in 18th century
- sometimes successful
- sometimes induced lethal smallpox - Jenner used dried pox from milkmaids (cowpox)
- vaccinia or vaccination
- example of live natural vaccine
- protects against smallpox (share surface antigens)
What must vaccines do?
- must induce clonal expansion in T and B cells
- induce formation of memory cells
- next encounter with antigen induces a secondary response
- faster, bigger, better
- prevents serious disease - adaptive immunity is key
Passive immunization?
- injection of preformed antibodies
- from recovered patients or from horses
- used in pre antibiotic days
- used today when toxins are already circulating (tetanus, diphtheria, snakebite)
- VZIG (varicella zoster immunoglobulin)
Ebola and passive immunization? would it work?
- maybe
- take someone who survived the illness, transfer serum to someone who is sick
Live natural viral vaccines?
- Jenners strategy cannot be applied to most pathogenic because there is no safe counterpart
- most viral vaccines used today
- killed or inactivated
- live attenuated
Live attenuated viral vaccines? (15)
- mutated so that it has reduced ability to grow in human cells
- no longer pathogenic in humans
- usually made by growing the pathogenic viruses in cells from non human species:
- select for variants that grow in non human host
- but less fit to grow in human host
Examples of live attenuated viral vaccines?
- MMR (measles, mumps, rubella)
- MMRV (proquad with varicella)
- Sabin (polio)
- yellow fever
- Varicella (chicken pox)
- rotavirus deliver orally
Advantages of live attenuated viral vaccines?
- better immunity because vaccine actually produces a limited infection
- can spread the attenuated virus to contacts
- herd immunity: phenomenon where those people who have no immunity against a particular pathogen are largely protected because the majority of population is immune
Disadvantages of live attenuated vaccines?
- can cause disease in immunosuppressed or immunodeficient individuals
- VAPP(vaccine associated paralytic polio)- reason OPV is no longer recommended
- Varicella- vaccine contra indicated in children treated with high dose corticosteroid, cancer, leukemia, lymphoma, non HIV immunodeficiency
- Rotavirus- rotavirus vaccine, precautions for altered immunocompetence - reversion to wild type or pathogenic virus
Killed viral vaccine?
- viral particles are chemically treated (formalin) or heated or irradiated
- influenza vaccine
- rabies
- salk polio vaccine
Advantages of killed vaccines?
- safe
- does not cause disease
Disadvantages of killed vaccines?
- must produce large amounts of virus
- incomplete inactivation
- no replication of virus, therefore immunity may not be as good
Polio vaccine?
- IPV (inactivated injection)
- no risk of vaccine associated with paralytic polio (VAPP)
- no mucosal immunity
- currently recommended in US - OPV (oral attenuated)
- 95% protection (life long)
- induces intestinal immunity
- herd immunity
- rarely VAPP
Subunit vaccines?
- include only the antigens that best stimulate the immune system
- in some cases these vaccines use epitopes, the very specific parts of the antigen that antibodies or T cells recognize and bind to
- use of only essential antigens decreases the chance of adverse reactions to the vaccine - may contain 1 to 20 or more antigens
- identifying which antigens best stimulate the immune system may be time consuming process and ambiguous - usually an antigenic surface structure
- induce neutralizing antibody
- prevent infection
- usually made by recombinant techniques
- Hep B vaccine
- Human papilloma virus (HPV) vaccine:
- protects against 6, 11, 16, 18
- helps protect against genital warts, precancerous cervical lesions and cervical cancer
Bacterial vaccines?
- whole bacteria
- toxins
- capsular polysaccharides (very good at stimulating T independent immunity, IgM)
Live attenuated bacterial vaccines?
- very few
- BCG Mycobacterium bovis (bovine tuberculosis) for TB (Mtb)
- efficacy varies in different populations
- not used in US - Salmonella
- defective in enzyme necessary for LPS synthesis
Killed bacterial vaccines?
- Bordetella pertussis
- when given with tetanus toxoid and diphtheria toxoid (DTaP), the presence of Bordetella organism causes stronger immune response to toxoids
- bad reactions - now acellular Bordetella preparation is used
- toxoid
- filamentous hemagglutinin, perfactin, fimbrial antigen
Toxoid vaccines?
- these vaccines are used when a bacterial toxin is the main cause of illness
- inactivates toxins by treating them with formalin
- such detoxified toxins, called toxoids, are safe for use in vaccines - vaccination with toxoid, results in production of protective antibodies that bind and neutralize the toxin
- toxin activity is destroyed (formalin)
- retains sufficient antigenic activity to protect agains diseases
- tetanus
- diptheria
Vaccines against capsular antigens?
- capsules:
1. contain strain and species specific antigens - polysaccharides (B cells)
- haptin (T cells)
2. also determine pathogenicity - block alternate path complement activation
3. aim of vaccine is to produce complement fixing anti capsular antibody
4. antibody response is usually T independent - babies don’t make good T independent immune responses, susceptible to infection of encapsulated bacteria
- polysaccharide is usually conjugated to carrier protein
5. conjugating the polysaccharide antigen to a protein carrier improves the vaccine (T cell response)
Why does conjugation of capsular vaccines improve the vaccine?
- more chance of class switching from IgM to IgG
- higher antibody titers
- generation of memory
- longer lasting immunity
- more effective in younger children
Examples of capsular vaccines?
- streptococcus pneumoniae
- Neisseria meningitidis
- Hemophilus influenzae
- conjugated vaccine is effective in reducing incidence and severity of childhood meningitis and pneumonia
Adjuvants?
- adjuvant is a substance that, when added to a vaccine, greatly enhances its protect against infection
- comes from latin “to help” - Alum, a mixture of aluminum, was the first vaccine adjuvant to be widely be used in US
- only in use until 2009
- ASO4- mixture of alum and bacterial lipid molecule that has been modified so that it does not cause disease - strong immune response requires some degree of inflammation
- during infection initiated by microbial products:
- activate macrophages
- increase expression of costimulators (if adjuvant is microbial)
- recruit inflammatory cells - purified protein vaccines induce poor immunity
- improved by adjuvants
- substances that induce non specific inflammation
- adjuvants also cause soluble antigens to aggregate
- clear slower
- increase phagocytosis
Benefits of Adjuvants?
- adding adjuvant reduces the amount of active component required in a vaccine
- reducing cost per vaccine
- making more doses available for public use - person may need fewer doses of vaccine containing adjuvant
- immune response is stronger and lasts longer - people with compromised immune systems, such as elderly or children, benefit from vaccines with adjuvants
- their immune system require an extra boost to provide protection - adjuvants are especially effective in boosting the immune stimulating effects of newer vaccine, such as those made with purified antigen
Newer vaccines: HPV?
- estimated 80% sexually active women acquire HPV by age 50
- quadrivalent vaccine (types 6, 11, 16, 18) licensed in september 2006
- females 9-26
- prevents or reduces incidence of:
- HPV induced cervical cancer
- cervical precursor lesions (dysplasia)
- vaginal and vulvar cancer precursors
- anogenital warts
HPV vaccine Gardasil 4?
- human papilloma virus (HPV)
- 100 different types
- low risk types 6 and 11 associated with low grade or benign cervical cell changes (precursors of cervical cancer) - vaccine consists of surface antigen
- current HPV vaccine (gardasil) licensed in June 2006, contains types 6, 11, 16, 18
- composed of virus like particles (VLPs) prepared from recombinant L1 capsid protein of HPV
- in 2009 gardasil was also recommended for boys
HPV vaccine Gardasil 9?
- specific for HPV types 6, 11, 16, 18, 31, 33, 45, 52, 58
- for both genders
HPV vaccine cervarix?
- specific for HPV 16 and 18
- HPV 16 and 18 cause about 70% of cervical cancers, each of the other oncogenic HPV types accounts for a small percentage of all cervical cancers
- approved for females only
Newer vaccines: zoster?
- vaccine licensed in 2006 for use in people aged 60 and over
- most effective at ages 60-69
- vaccine prevents shingles in 50% of vaccinated individuals
- vaccine prevents post herpetic neuralgia in 67% of vaccinated individuals - does not treat shingles or post herpetic neuralgia
What diseases have been eradicated?
- smallpox officially eradicated
- official in 1980 - polio in the near future
- last case in US was 1979
- western hemisphere polio free in 1994
- last isolated of type 2 was India in 1999
- global eradication goal keeps getting pushed back
- goal is 2018-2019
Malaria vaccine?
- RTS, S/A01
- not very successful
- phase 3 trial
- limited effectiveness, wanes over time
- keep adding booster doses, need periodic boosters to be somewhat effective
- doesnt protect babies
- phase 4 to be implemented