Transcript Vaccines - California State University, Fullerton

Vaccines
Polio - close to eradication. In 2001 >1000
cases worldwide; last wild case in
Americas in Peru in 1991
Learning objectives
• Compare the attributes of available virus vaccines
compare to the ideal vaccine
• Explain the advantages and disadvantages of the
various types of virus vaccines
• Explain how smallpox was eradicated and why
most other virus diseases cannot be eliminated
with the same strategy
Outcomes of immunization
• Sterilizing immunity - gets
virus before it can enter
any cells
• Transient Infection - no
symptoms
• Controlled infection virus establishes and
multiplies but does not
spread
– Levels below
transmissibility levels
Vaccines have saved
lives and reduced
cases
Ideal Vaccine
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Safe
Inexpensive
Heat-stable
Oral administration
Effective in all ages
Single dose
All strains sensitive
Induces systemic and mucosal immunity - CMI and
antibody
Aimed at stimulating both humoral and
CMI
• Antibody is primarily
aimed at surface capsid or
env proteins of free virus
• CMI can be aimed at
internal proteins expressed
with MHC1 and these may
be more conserved among
subtypes
• How do you measure each
response?
• How do you measure
protection?
Eradication of smallpox
1) No animal reservoir
2) Lifelong immunity(no antigenic shift or drift)
3) Subclinical cases rare
4) Infectivity does not precede overt symptoms
5) One Variola serotype (monotypic vs heterotypic)
6) Effective vaccine
7) Major commitment by governments to
surveillance and containment (length of incubation
period)
Types of vaccines
• Inactivated - formalin treatment
– Serum antibodies
– Can be used on
immunodeficient patients
• Live-Attenuated - from nature
or by passage in culture
– Polio
• Temp sensitive so poorer
replication at 37
• IRES mutants
• Oral administration and
IgA production
Polio eradication
• Cases in Dominican Republic
and Haiti 2000/01
• Subunit - gene cloning
products (HBV)
• Peptide epitopes (FMD)
• Vaccinia/pox vector
vaccines - replicates
• DNA vaccines - naked
• Pseudovirions - env
protein of vaccine virus
• Replicons - non
replicating virus carries
gene from “vaccine” virus
For each type of vaccine
• Advantages
• Disadvantages
Can an HIV vaccine
be effective?
• DNA vaccine for env/gag
augmented with IL
• Challenge with SHIV
• 1 of 8 monkeys developed
disease after 20 weeks
• Showed loss of CTL against a
gag protein - single nucleotide
escape mutant predominated
• Rapid emergence wins immune
battle
• http://www.niaid.nih.gov/daids/
vaccine/info.htm
HPV Type 11 vaccine
• Type 11 low risk but gives
warts
• Capsid protein can
assemble into VLP
• Immunize seronegative
women with VLP and
measure ab and CTL
responses
Lancet Nov. 2004 Bivalent vaccine L1
VLPS to HPV16/18
Clinical Trials - Would you volunteer?
http://www.clinicaltrials.gov/