Vaccines

Immunological memory and incubation periods

Memory response is faster than incubation period for many

infections providing protection against disease

Some infectious agents have very short incubation periods and

insufficient antibody levels may be present.

The use of boosters and/or seasonal vaccinations help to

maintain antibody levels above protective levels

Live, Attenuated Vaccines used

Measles, mumps, rubella, polio, chickenpox, yellow fever,

TB

Live, Attenuated

Organisms are able to replicate, but unable to cause disease or cause very mild illness

Live, Attenuated produced by:

growing for prolonged times in abnormal conditions, deleting key virulence genes: herpesvirus vaccine for swine lacks thymidine kinase which is necessary for growth in neurons

Live Attenuated vaccines:

Pros

Provide prolonged exposure resulting in better immune response and better chance of memory

Replication may be able to occur in mucosal surfaces where initial contact with pathogen is most likely to occur --triggers production of IgA antibody

Triggers a cell mediated response to viruses replicating within cells as well as a humoral response

Live Attenuated vaccines:

Cons

Passing the weakened virus to immunocompromised

individuals which may become ill

Not normally given to pregnant women due to possible risk of

transmission to fetus

A rare but possible chance of reversion

A risk of complications that are normally associated with the

natural disease

Inactivated/Killed vaccines used in

paratyphoid fever, typhus fever, flu shot,

hepatitis A, cholera, plague, original pertussis

Inactivated/Killed

-must be careful to maintain epitopes (heating not as

good so alkylating agents are often used)

-Predominantly humoral (Antibody) response only

-Require boosters

-Generally safer but still risk that chemical fails to

inactivate (First Salk vaccine)

Subunit Vaccines

Contain just a specific purified molecule from

pathogen

Toxoids

inactivated toxin from bacteria in

which illness is primarily from a Toxin (tetanus,

diptheria, current pertussis)

Capsule

many virulent bacteria have capsule

to protect from immune system—antibodies

to this cause clearance by complement or

opsonization (Strep pneumoniae; Neisseria

meningitides; Haemophilus influenzae)

Pathogen attachment proteins:

Hepatitis B

surface antigen (HBsAg gene cloned and

expressed in yeast); Pertussis FHA protein for

attachment to tracheal cilia

Subunit Vaccine Cons

Subunit vaccines are poorly immunogenic

without the rest of PAMPs to stimulate

response.

• Adjuvants may be used to increase

antigenicity

• Most subunit vaccines are

conjugated together to increase

immunogenicity of the vaccine.

• Newer strategies rely on MAPs

(multip-antigen peptides) to

increase the size, complexity, and

number of antigens to a given

pathogen

DNA Vaccines

Virulence genes from

pathogens are inserted into

plasmid DNA, Intramuscular injection of

DNA followed by uptake of

DNA by muscle cells and

dendritic cells

DNA Vaccine PROS

Protein is expressed in natural form

—no chemical modification

induce both branches of immune

system

prolonged expression allows for good

immune response/memory so no

boosters

DNA’s stability makes it more

suitable for mass vaccination (long

term storage is an issue for some

vaccines)

SARS vaccine has been tried in mice

West Nile vaccine approved for

veterinary use only

RNA Vaccines

Gene for proteins of interest is cloned

into plasmid vector. Large amounts of

mRNA produced from cloned DNA

(modified nucleotides may be used to

increase RNA stability)

mRNA encapsulated into lipid

nanoparticles for delivery into cell

mRNA is translated in cell and protein

is expressed and processed by MHC

May be fastest means to generate

vaccine

Recombinant Vector Vaccines (Vet Med, few for humans)

Chimerics using attenuated or harmless viruses containing genes

for other more dangerous viruses

Vaccinia, polio, or adenovirus is often used as the vector

Vesicular stomatitis virus (VSV) contain Ebola genes was

used during the West Africa Ebola outbreak in 2015!

rVSV-ZEBOV