Chapter 11

Immunological Memory and

Vaccination
Part 2

Comparison of Maximum and

Current Morbidity
Disease

Maximum cases (year)

2003 U.S. cases

Diphtheria

206,939 (1921)

Measles
Mumps
Pertussis
Polio
(paralytic)
Rubella

894,134 (1941)
152,209 (1968)
265,269 (1934)
21,269 (1952)

0
0
11,647
0

57,686 (1969)

Tetanus*

1,560 (1923)

~25

*deaths in 1923 v. cases in 2003

Vaccination to prevent infectious

disease
It has been claimed that vaccination has saved more
human lives than any other medical procedure.
Edward Jenner: 1796 smallpox to today using
recombinant DNA technology
Today? Jenny McCarthy
Retracted autism study an 'elaborate fraud,'
British journal finds
Dr. Andrew Wakefield had his medical license revoked
with a statement identifying deliberate falsification in
the research published in The Lancet, and is barred
from practicing medicine in the UK

Protection against smallpox

Initial smallpox vaccines: variolation give them a
little bit of the real thing!
- Resulted in death of about 1/100, whereas natural
spallpox acquisition = 1/4
Enter: cowpox (vaccinia) virus.
Latin vaccus = cow.
So, the first vaccine was exclusively named as such
because of smallpox/cowpox, but now we use it for all
immunizations
It remains the only infectious disease of humans that
has been eradicated worldwide by vaccination
a) Evolves slowly, b) live virus vaccine, c) only infects
humans

Viral Vaccines
Cannot use Jenners strategy for most viral
pathogens since they dont have a safe relative
Instead, viral particles that cannot replicate or
heat, formalin, or irradiation-treated viruses
(inactivated virus vaccine) used
Ex) influenza, rabies
Alternatively, a naturally-occurring, mildly
pathogenic strain or a recombinant strain
(genetic engineering) can be used = live
attenuated virus vaccine
Ex) measles, mumps, yellow fever

Poliovirus
Fewer than 1% of infections with polivirus cause
disease, but it is a BAD one.
Multiple strains = same effect, so there was a
need for a broad-spectrum vaccine
Salk vaccine = killed virus of 3 strains (1955), but
by 1963 Sabin introduced a live version.
Does it work? Last recorded case of polio in the
US was in 1979 (thats 3 years pre-me)
Developing countries still struggle to eradicate it,
so vaccination still happens, but do we vaccinate
against smallpox anymore?

Vaccination can inadvertently cause

disease
So, vaccines are not entirely without
risk.
People without immune systems or
compromised immune systems can
actually get the disease from the
vaccine
Ex) Polio
Also, there are some people who
have negative reactions to the
adjuvants

Subunit vaccines
Hepatitis B virus (HBV) immune responses
involve protective, neutralizing antibodies
against a surface antigen
Subunit vaccine = even then there was
concern that there would be infected patients
Instead = insert gene coding HBV surface
antigen into bakers yeast then grown in mass
culture.
Since 1986, about 85% of people with
immunity to HBV comes from that vaccine

Rotavirus vaccine
Wheel-shaped (rotaterota) was described in 1973
and is a leading cause of severe childhood diarrhea
Still took more than 30 years to develop an effective
vaccine. Why?
Frequent mutation, multiple coat proteins it is a LOT
like influenza, but affects GI
Enter: Jennerian science RotaTeq vaccine has five
cattle rotaviruses that are not human pathogens and
they are genetically engineered to express human
VP4 or VP7 on their surface.
The key here: cheap and easy to deliver to poor
countries

Bacterial vaccines
First live-attenuated bacterial vaccine:
Mycobacterium tuberculosis
Since: Salmonella typhi (typhoid fever) but in a
human-driven mutated strain that cannot express the
LPS toxin chain!
Some pathogen toxins are the big problem, not so
much bacterial replication itself: diptheria and tetanus
- Each vaccination for these = a booster or a toxoid (a
lot like viral subunit vaccines)
Any vaccine against a Gram+ bacteria needs to help
complement penetrate their capsule, which is a
challenge.

Conjugate vaccines
If a vaccine only activates part of the immune
response, it doesnt offer all that much protection (i.e.
need B and T cells)
Ex) Polysaccharide vaccine for Meningitis no source of
peptide for MHC-II presentation, so antibody response
was weak and T-cell response was non-existent
Solution? Conjugate vaccines = conjugate the N.
meningitidis polysaccharide to either tetanus or
diptheria toxoid. Linking epitopes that can activate both
T cells and B cells
Similar techniques are used against pneumonia-causing
agents too

Adjuvants
Subunit and conjugate vaccines of one or a few purified
peptides DO NOT activate the innate immune response
because they are not detected by TLRs and other
receptors.
To get the attention of the innate immune response,
adjuvants are used and these trigger inflammation
Ex) DTP: diptheria toxoid, tetanus toxoid, and B. pertussis
bacteria (combination vaccine): bacteria induces
inflammation AND the toxoids become targets for both
lymphocyte types
Alum is used as an adjuvant (aluminum hydroxide), but it is
weak (used since 1924), but there other safe ones in
development (see Fig. 11.21)
Experimental studies have used mercury, lead, and arsenic
to do the same, but clearly those have major side effects.

Genomes and vaccines

As we sequence genomes of
pathogens, we are better able to
target them.
For example, N. meningitidis has the
ability to express human proteins on
the surface to hide from human
immune systems.
Solution: We found the genes that
allow them to do this, so we can
make a vaccine that targets those

Worldwide Influenza
AKA how we almost destroyed the world 5 year ago because we
are dumbasses.
World Health Organization subsidizes companies for providing
vaccines against potentially pandemic pathogens (say that 10x
fast)
But not everyone gets a flu shot and the flu evolves rapidly, so
sometimes by the time you get it, its already changed.
In March 2009, swine flu (a novel H1N1 strain) hit Mexico and
North America. The manufacturing of a vaccine began on June 7
as the epidemic began. The epidemic peaked in October 2009,
but the vaccine was not available and delivered to patients until
December 2009 and January 2010. OOOOOPS!
Fortunately, it wasnt as deadly as it could have been but why
did it take so long????
- $$$ and Proprietary Science!
- Now we have a mandated system in place where dozens of
companies will synthesize enough vaccine in a single day to
vaccinate all of the USA if a new one arrives.

Vaccines and prevalence

If the pathogen is gone = no need to
continue vaccination
If a pathogen returns, start
vaccinating again.
If a pathogen returns and people for
some odd reason no longer trust a
vaccine.well
- Whooping cough is back
- Measles are back
Herd immunity

Chronic infectious disease and

vaccine challenges
The vaccines previously listed are against
acute infections. Chronic is a bigger
problem
Ex) Plasmodium, M. tuberculosis (15% that
arent protected by cow tb), and HIV
interfere with our immune systems and
make them work in their favor
FORTUNATELY: genome sequencing is
leading to better chances of vaccinating
against these things

The Perfect Vaccine

100% effective
Oral dosage form
No adverse effects
Highly immunogenic
life-long immunity
no boosters required

Cheap
Stable at room temperature
no cold chain required

Vaccine public scrutiny

Two big differences make the development and success of a
vaccine much more difficult than that of a drug
- 1) drugs are given to people who know the pain of the
disease and are more willing to accept it
- 2) people trust their physicians, but not smart scientists
advising a government program
- I am adding 3) (your book wont go here), but
pharmaceutical $$$$$ is also a player
Drugs AND vaccines can have unwanted side effects, and a
risk/benefit analysis is always warranted (ex) rotavirus and
bowel obstruction
Fortunately, herd immunity will afford protection of people
who refuse to protect themselves, but only until a threshold
at which too many people take the no vaccines route, then
that protection is lost

Most important website

ever.

http://howdovaccinescauseautism.com/