what are some of the types of vaccine technology used?

• inactivated whole virus
• inactivated whole bacteria
• live attenuated viral or bacterial vaccines
• conjugate vaccines: poorly immunogenic carbs conjugated to a carrier protein
• recombinant protein vaccines: cloned antigens expressed and purified in lab (ie: HepB)
• virus-like particles: capsid protein expressed in absence of other viral genes

• immunopotentiators that enhance the immune responses to vaccines
• always licensed in combo with a specific vaccine
• alum is presently the only adjuvant licensed by the FDA for US vaccines

what is the only adjuvant licensed in the US for vaccines?

• serum Abs: mostly IgG
• secretory IgA (main Ab of the mucosa: respiratory, GI, GU tracts)
• cell mediated immunity stimulated

what are the components of the immunological memory triggered by vaccination?

• accelerated immune response upon pathogen exposure
• enhanced immune response
• higher affinity Abs vs naive subject response
• long lived B and T memory cells elicited

how does the immune response differe between PS and a PS-protein conjugate vaccine?

in PS vaccine:

• PS binds BCR stimulating differentiation into plasma cell, which secretes low affinity IgG2 and IgM
• no production of memory cells
• no recruitment of T cells: T CELL INDEP'T

in PS-protein conjugate vaccine:

• bacteria antigen binds BCR
• protein component taken up, digested, and displayed on MHC class II peptide for T cell stimulation
• B cell expresses CD40R which binds T cell CD40L for further downstream activation of B cell
• B cell expresses B7 (CD80/CD86) (costimulatory ligand) that binds CD28 receptor on T cell
• PS specific memory cells are produced
• differentiated plasma cell produces higher affinity IgG1 and IgG3

what are examples of licensed conjugate vaccines in the US?

• Hib: capsular PS conjugated to carrier protein of tetantus toxoid derivation (PRP-T)
• Streptococcus pneumoniae + mutant tetanus toxoid protein
• Neisseria meningitis conjugated to diptheria toxoid

what are some important considerations for vaccines and the potential range of immune responses?

• age: elderly/infants immune response weaker
• route of administration: parenteral (im, sc, etc) vs mucosal (oral, intranasal)
• genetic makeup of host
• environmental effetcs on host
• varying response to parental (higher in developing) vs oral (higher in industrialized) vaccines in developing vs industrialized nations
  

• bind to antigen
• neutralization of viruses (measles, yellow fvr)
• neutralizationof toxins (tetanus, diphtheria, cholera)
• complement mediated bactericidal killing
• opsonophagocytic killing
• Ab dept cellular cytotoxicity (ADCC): often mediated by NKs

• prevent attachment of pathogens to mucosal surface
• neutralize toxins
• intracellular neutralization of viruses

what is the mechanism of action of the attenuated measles virus vaccine?

• sc administration
• elicits serum plaque reduction neutralizing (PRN) Abs that bind Hemagglutinin (H) protein by which virus binds to receptors on cells
• stimulates CMI via CD8+ cells
• effective when administered as small particle aerosal in pts > 10mos
• ineffective as large nasal droplets

where in the body does oral immunization induce response?

• proximal small intestine
• ascending colon
• mammary and salivary glands

where in the body does rectal immunization induce response?

• rectum
• distal colon

where in the body does nasal or tonsillar immunization induce response?

• upper airway mucosa
• saliva, nasal secretions
• female genital tract (vagina, cervix)

why is an adjuvant an attractive option for H1N1 vaccine?

• dose sparing: may be able to immunize with low doses of vaccine
• single dose regimen: may be able to achieve protective titers in non-elderly adults with 1 dose of adjuvanted vaccine

• safe in all ages and immunocompromised
• efficacious in all ages, incl young and old
• single dose
• protection early and long lasting
• adminstrable w/o needle and syringe
• no cold chain needed
• combinable w other vaccines

immunogenicity and reactogenicity

powerful stimulation of the innate immune system, accompanied by release of various cytokines often results in fever, malaise, other adverse effects

• funds
• cold chain
• poor infrastructure
• poor acceptance