*M40: Vaccines Flashcards
a. Vaccine: a suspension of microorganisms (live attenuated or killed) or fractions of microorganisms, administered to induce immunity and prevent disease.
b. Immunization: artificially inducing an immune response or providing protection against an infectious disease.
c. Active immunization: inducing the body to mount a protective immune response.
d. Passive immunization: transferring exogenous antibody for temporary protection.
-
e. Toxoid: Bacterial toxin rendered non-toxic and used to stimulate anti-toxin antibodies.
f. Adjuvant: a substance sometimes mixed with the vaccine components to induce a stronger immune response; particularly important when a subunit antigen is used (“danger” signal).
g. Sterilizing immunity: an immune response that completely eliminates the infection.
h. Herd immunity: the resistance of a population to an infectious agent due to the immunity of a high proportion of the population
-
Effectiveness of vaccination:
Example: In the US, measles killed 3000 people per year and caused 48,000 hospitalizations prior to immunization. When immunization rates declined a decade ago, there was an outbreak of 55,000 cases, with 11,000 hospitalizations and 125 deaths. Following introduction of a vaccine in the US, a number of infectious diseases were reduced so far as to be virtually eliminated within 5-10 years (e.g. polio, diptheria, neonatal tetanus, measles, rubella).
-
Immunologic responses to vaccines
a. The primary immune response to an antigen takes 7-10 days—T cells must be primed and proliferate, help is then provided to B cells or CD8 T cells, and these cells proliferate. In the absence of an actual infection, the cells become memory cells. Upon challenge with a microbe, a secondary response, which is much faster and more robust, is mounted and the infection is eliminated or disease is averted.
b. Best case scenario for developing a vaccine: prior infection (once) protects against subsequent infection.
-
Immunologic responses to vaccines
c. Live vaccines can induce antibodies as well as effector T cells, while subunit or killed vaccines primarily induce antibody responses. Most vaccines that are used today work by inducing a strong antibody response that can inactivate the toxin or prevent viruses from entering cells. There are many infectious diseases for which an effective vaccine has yet to be developed. These infections are often complex, with protection dependent on various aspects of the immune response, and have immune-subverting mechanisms. Also, chronic infections, which can persist in the face of the immune response, are very difficult to vaccinate against.
-
Vaccines not available for some of the world’s biggest killers
Vaccines urgently needed for diseases such as: Tuberculosis Malaria HIV Worm infections Diarrheal diseases Respiratory infections Sexually transmitted diseases (gonorrhea, Chlamydia, syphilis) Trypanosomal infections
-
Safety issues:
Modern vaccines are safe and effective, but there are risks. Each vaccine is associated with some adverse effects, mostly mild, but occasionally severe. There has been substantial controversy regarding safety of vaccines, and some parents choose not to vaccinate their children because of fears about vaccine safety. Overall, the benefits of vaccination far outweigh any risks. Vaccine use comes under frequent review, and modifications to reduce risk occur. For example, the acellular pertussis vaccine is now used instead of the killed whole pertussis vaccine, because there are many fewer side effects. Inactivated polio vaccine is used now instead of live attenuated polio vaccine, because the only polio cases (~5/year) that were seen in the US in recent years were due to the vaccine.
-
Herd immunity: effects of vaccination on the public
a. When a large group of people (i.e. school-age children) are vaccinated, there is little reservoir for the infectious agent. Thus, even those children not vaccinated are “protected” from disease, simply due to the fact that there is less chance to be infected.
b. Some live vaccines can be passed to other, non-vaccinated individuals
-
Live attenuated microorganisms
a. microbe is rendered relatively avirulent (frequently by repeated passage in vitro).
b. replicates in the recipient, inducing a strong immune response. Frequently, protection is long-lived and only one dose is necessary.
c. A more comprehensive immune response may be induced by live vaccines.
d. Examples: measles, mumps, rubella, smallpox, BCG, oral polio. Some safety issues.
-
Killed/inactivated microorganisms
a. organism is killed, and used as a vaccine. Usually requires more than one dose to induce strong responses, and boosters are also necessary.
b. Usually induces an antibody response.
c. Examples: whole pertussis, inactivated polio vaccine, hepatitis A.
-
Subunit vaccines
a. Purified components of microorganisms, such as toxoids, recombinant antigens, polysaccharides conjugated to carrier proteins.
b. Usually repeated doses are needed, with adjuvant, and antibody responses are induced.
c. Examples: hepatitis B vaccine, tetanus, diptheria, Hib, acellular pertussis.
-
Other vaccines
a. Other vaccines available and used as needed
Some vaccines are delivered to travelers to other countries as protection
• e.g. typhoid vaccine
Some vaccines are delivered to at risk subpopulations in the US
• rabies vaccine, pneumococcal vaccine, anthrax
Some vaccines are commonly used in other countries, but not in the US
• e.g. BCG (vaccine against tuberculosis)
Booster for tetanus and pertussis (pertussis as booster for adults is relatively new)
b. Future vaccines
DNA immunization
Heterologous vectors (viral or bacterial)
More subunit and recombinant vaccines
-
MMR vaccine: Mumps, measles, rubella
Mumps:
a. Virus characteristics: Family Paramyxoviridae, Genus Rubulavirus
- Single stranded negative sense RNA virus
- One serotype known
b. Disease
- Acute viral infection with swelling and tenderness of the parotid and salivary glands
- Symptoms: fever, malaise, headache, involvement of parotid and salivary glands
- Usually fairly benign; complications can include meningitis and epididymo-orchitis (rare before puberty).
c. Vaccine (1967)
- Attenuated virus grown in chick embryo cell culture
- Single immunization produces anti-mumps neutralizing antibody in >95% children
- Given at >12 months of age, to avoid maternal antibodies
-
MMR vaccine: Mumps, measles, rubella
Measles:
a. Virus characteristics: Family Paramyxoviridae, Genus Morbillivirus
- Rubeola virus (also called measles virus)
- Single stranded negative sense RNA virus
- Important membrane glycoproteins include hemagglutinins and the F (fusin) protein
b. Disease: extremely contagious, still a major killer of children in the developing world
- Respiratory transmission
- Incubation period 10-14 days
- Clinical manifestations: malaise, fever, runny nose, respiratory symptoms (cough) precede the rash. Koplik spots also precede rash (bluish gray specks on a red base inside the mouth).
- Rash: usually begins on face, proceeds down body, with extremities last. Erythematous and maculopapular; usually lasts 5 days.
- Entire illness 7-10 days
-
MMR vaccine: Mumps, measles, rubella
Measles:
c. Complications:
- Respiratory tract complications (secondary bacterial infection) neurologic (encephalitis) with possible long term effects
- Long term immunosuppression, resulting in enhanced susceptibility to other infections
d. Vaccine (1963)
- Live attenuated virus grown in cell culture
- Immunity is probably antibody and T cell-mediated
- Long lasting immunity
- Given at 12-15 months of age because of maternal antibodies
- Can be a problem in other countries where measles is still prevalent—vaccination of younger children is sometimes performed, but these children may be less protected
-
