Biology 216 - Lect8
Immunization and Vaccines
Objectives: Principles of vaccination and vaccine development
Balance between Host and Microbial factors:		
Host (vaccinated) ----------------Microbe
I. Definitions:
Immunization - Increase resistance to disease by active stimulation 
	of immune system or passive transfer.
Vaccine - Specific microbe or product which induces protective immunity.
 Ideally - antimicrobial factors and memory cells
Historical - 	
1500s - Chinese, dried crust of smallpox inhaled or into scratches. (Variolation)
1800 - Edward Jenner - milkmaids immune to smallpox. Vacca (cow).
1800s - Old culture of Pasteurella protected from fowl cholera. (attenuated)
1890 - Passive immunity - Emil von Behring.
1890 - Eli Metchnikoff - phagocytes more active in vaccinated animals. (CMI)
1950s - Macfarlane Burnet - Clonal selection
1980s - Tonegawa - cassettes of genes.
II. 4 basic types of immunization.
A. Natural active - Disease or colonization induces immunity 
	- mumps, measles, GpA strept
      Constant exposure: Hib, diphtheria
B. Artificial active - administration of vaccine to induce 
	protective immune response.
     1. Killed organism or part of organism.
	Organism - pertussis, typhoid (old vaccine), cholera
	Product - toxoid (immunologically similar, non-toxic,
		 formalin treated toxin), capsule
	 Negative aspects: large dose, incomplete inactivation (Salk polio)
     2. Live attenuated - avirulent strain - Sabin polio, measles, mumps....
	By passage in vitro (anthrax, BCG, S. typhi ty21)
	Genetic engineering (A-B+ V. cholerae, HgR into A gene in vitro)
	Negative aspects: Storage lability; fear of reversion ex. M13; 
		immunocompr and pregnant.
C. Natural passive - immunity from one host passed naturally to another 
	(Emil von Behring).
	IgG through placenta (Hib, tetanus)
	Short protective duration - Ab and cells dilute out.
D. Artificial passive - immunity from one host artificially passed to another.
	Anti-tetanus (humans); Anti-diphtheria (equine); Rhogam
	For IMMEDIATE protection.
III. Development and administration of vaccines.
A. What is protective Ag? Must understand pathos of disease.
	Ex. Toxoids (formaldehyde inactivated tetanus); Surface Ag (capsule)
B. Is protective Ag immunogenic? Recognized as foreign and immune response mounted.
	Ex. ST; N. mening GpB capsule; old Hib (pure capsule)
C. Is disease of sufficient severity and frequency?
	Ex. Whooping cough side effects; botulism.
	A vaccine may be justified for at-risk population only
		 (Ex. Rabies - vets, bot-research, Hib age5)
D. Are there multiple serotypes of protective Ag? 
	Tetanus (1); Diphth (1); Polio (3); S. pn (84)
E. Adjuvant to increase immune response
     MOA - gradual release; stimulate lymphocyte influx; 
	delay Ag clearance; stimulate Ag processing.
	1. Freund (complete and incomplete) - not in humans
	2. Alum (aluminum hydroxide) - Ex. dT
	3. Combination where one is adjuvant - DPT 
		( new acellular pertussis - aP with alum)
	4. Exptl - liposomes; muramyl dipeptide
IV. Vaccines available - Handout  (note following new vaccines or changes)
Hib: 1985 capsular for age 2 yr; 1988 capsule-diph thoxoid conjugate 
	for 18 month; 1991 - 2,4,6,18 month
Pneumococcus protein conjugate licensed 
Hepatitis B recombinant
Rotavirus (discontinued)
Varicella (chickenpox)
Polio killed vs attenuated