ORGB 423 Lecture Notes - Lecture 8: Smallpox Vaccine, Measles Vaccine, Attenuated Vaccine
12 Jun 2018
School
Department
Course
Professor
MIMM466 Viral Pathogenesis
2018-03-26 LEC 30 & 31 Viral Vaccines
Brian Ward
History
- Probably about 10-15% of us would not be here if it were not for vaccines. Diseases used to wipe out many
more people – PESTILENCE is one of the 4 horsemen of the apocalypse
- Measles and Smallpox were old world diseases, and did not exist in SA until the conquistadors introduced it
in the 15th century
o Prior to its introduction (1520), the New World population was ~3 million
o After its introduction (1600), the population was about 65 000
à The mortality rate of measles in a virgin soil epidemic can be as high as 70%
- Viruses have largely “kicked our butts” throughout history
o HIV is still kicking our butt. 39 million have died so far
o No wonder that often disease, namely, respiratory
(easily transmittable) viruses are a central feature in
doomsday stories (Oryx and Crake, World War Z)
- The probability of another catastrophic influenza pandemic
occurring is basically 100%, and it would kill hella people
Who first thought of the idea of vaccination to prevent infections?
- Ancient civilizations, such as the Chinese (VARIOLATION),
and the Middle East (LEISHMANIZATION)
- Variolation entered Europe via Constantinople (Istanbul)
o Lady Mary Montagu introduced it a century before Jenner
- The development of several techniques and ideas lead to the gradual advancement of vaccination
o Ancient civilizations “crude” vaccination/variolation between 14th-18th centuries
o Jenner’s smallpox vaccine and the idea of cross-species protection in the 18th century (England)
o Pasteur’s rabies vaccine used the technique of animal passage to attenuate a virus in the 18th century
(France)
o The idea of germ theory (1 pathogen = 1 disease) and technique of using broth cultures developed in
the 19th century (Europe)
o The techniques of toxin isolation and using eggs as crude cell cultures were developed in the 20th
centuries (World)
§ Egg culture gave us the pertussis, tetanus, YF, and influenza vaccines
• To this day, YF and influenza vaccines are still made in eggs
o There was a “massive explosion” post-WWII after we discovered DNA/RNA, the attenuation of
organisms, began to understand basic immunology, and refined cell culture
o The world’s first recombinant vaccine (i.e. developments in molecular biology) was for Hep B
- Right from the beginning, vaccines had an element of salesmanship to get people to come forward for
vaccination. The Pasteur institute had 2 pens of sheep out front for people to see:
o 1 pen was immunized = happy, healthy sheep
o 1 pen was not immunized = dead/dying sheep
1792 VIRGINIA SMALLPOX LAW: Wrt quarantine, it stated that no infected person should come in
contact with an uninfected, non-immunized person. In fact you were not allowed to leave your house if you
were infected
How did early vaccinators get vaccinia virus (i.e. smallpox vaccine) to the New Wold via boat?
SERIAL INNOCULATION: They would basically bring a bunch of calves aboard, and pass it through
them until they reached land. They ensured careful separation of naïve and infected animals.
Spectrum of viral illnesses
- 130+ viruses are known to infect humans (not including different genotypes of the same virus)
o And we keep discovering new ones
- >320 000 viruses infect mammals
o Bats alone carry a ton of viruses
Immunity to viruses – the goals of vaccination
- If you have no ability to make Abs whatsoever, the only pathogens you really die from are:
o Enteroviridae
o Encapsulated bacteria
o G. lamblia
§ People who cannot make Abs do NOT suffer more frequent, or worse disease from any other
pathogens
- This basically tells us that while Abs are important for preventing infection, they are clearly not necessary in
most cases
- It’s actually cellular immune responses that are critical for all viruses, and innate immunity to keep you alive
until those cellular responses can kick in
- Despite this, most of our efforts and vaccination or diagnostic strategies focus on Abs to provide
immunity/protection
o Abs are sufficient, not not necessary to protect from most viral diseases. People without them can still
be protected for life
Ward got H1N1 in 2009, so he withdrew his blood and was approached by 13 groups wanting to test his
serum. Only 2 labs found a sufficient Ab response, but all found that his T cells were way elevated. He
recovered (obviously), despite a weak Ab response – his T cells took care of it!
à The ultimate goal of vaccination is to avoid pathology, one way or another. This could be achieved by:
- Eradicating the pathogen (smallpox, measles, polio)
- Providing sterile immunity, i.e. the pathogen cannot colonize the host (ex: Ebola, oncogenic HPV, sometimes
this immunity is sex-limited like in the case of rubella/Zika/Herpes)
- Preventing the pathogen from arriving at its target tissue (ex: polio, HepA, HepB all get stopped in the blood
first)
- Preventing the consequences of infection (ex: colonization by non-oncogenic HPV, antitoxins for tetanus and
diphtheria)
- Modifying the disease itself, ex: preventing its transmission (ex: the measles vaccine + IgG)
Several characteristics of viral disease need to be taken into account when designing a vaccine:
- Is it monotypic? (i.e. you get infected, you live or you die, if you live then you are immune for life) (ex:
measles, smallpox)
- Is it monophasic? (i.e. re-infection is very rare)
- Number of variants/genotypes
- Genetic stability/lability
- Target tissue
- Pace of infection progression (ex: smallpox is rapid, HIV is slow)
- Is there any latency? (ex: herpes)
- Is their genome integration? (ex: retroviruses)
- What kind of immunity is required?
Several characteristics of viral disease need to be taken into account when prioritizing vaccination and
designing programs
- Is there a non-human reservoir?
- Vulnerable populations
- Pace of infection
- Reproduction rate (i.e. R value, pandemic potential)
Document Summary
Probably about 10-15% of us would not be here if it were not for vaccines. Diseases used to wipe out many more people pestilence is one of the 4 horsemen of the apocalypse. The mortality rate of measles in a virgin soil epidemic can be as high as 70% Viruses have largely kicked our butts throughout history: hiv is still kicking our butt. 39 million have died so far: no wonder that often disease, namely, respiratory (easily transmittable) viruses are a central feature in doomsday stories (oryx and crake, world war z) The probability of another catastrophic influenza pandemic occurring is basically 100%, and it would kill hella people. Ancient civilizations, such as the chinese (variolation), and the middle east (leishmanization) Variolation entered europe via constantinople (istanbul: lady mary montagu introduced it a century before jenner. Right from the beginning, vaccines had an element of salesmanship to get people to come forward for vaccination.
