A Variety of Vaccines: A History of Vaccine Development

Summary

This Health Care Triage episode explores the history of vaccines, from the first inoculations in the 1700s to modern advancements. It covers the development of various vaccine types, including live attenuated, inactivated, toxoid, subunit, and conjugate vaccines. The script discusses the use of adjuvants to enhance vaccine effectiveness and the shift from using animal tissue to human cell lines in vaccine production. It also highlights the importance of vaccines in eradicating diseases like smallpox and polio.

Takeaways

• 📚 The history of vaccination began with the use of cowpox material to induce smallpox immunity in the late 1700s.
• 🔬 The first laboratory-developed vaccine was created by Louis Pasteur in 1879, who discovered the process of weakening cholera bacteria by accident.
• 🌡 Various methods were used to weaken viruses and bacteria, including heat treatment, chemical exposure, and the use of formalin.
• 🧬 In 1926, aluminum salts were found to increase the effectiveness of the diphtheria toxoid, leading to the use of adjuvants in vaccines.
• 💉 There are different types of vaccines: live attenuated, inactivated, toxoid, subunit, and conjugate, each with specific methods of inducing immunity.
• 🌟 Live attenuated vaccines contain weakened live viruses that cannot cause serious illness but can revert to disease-causing forms.
• 🔄 Inactivated vaccines are killed with heat or chemicals and require multiple doses and boosters for effective immunity.
• 🦠 Toxoid vaccines target the toxin produced by disease-causing germs, such as diphtheria and tetanus.
• 🧬 Subunit and conjugate vaccines were developed for more targeted immune responses, with the latter improving the effectiveness in young children.
• 🌐 Production techniques evolved significantly, including the use of chick embryos and human cell lines for virus cultivation.
• 🏥 The first combined vaccine was introduced in 1948, and the first subunit viral vaccine for hepatitis B was developed in 1981.

Q & A

What was the significance of the cowpox material in the history of vaccination?

The cowpox material was used in the late 1700s to induce smallpox immunity, marking the beginning of the world's first vaccinations.

Who was the scientist responsible for the first laboratory-developed vaccine?

Louis Pasteur was responsible for the first laboratory-developed vaccine in 1879, which was a cholera vaccine.

How did Louis Pasteur accidentally discover the concept of a weakened vaccine?

Louis Pasteur discovered the concept when his assistant forgot to inject chickens with a fresh batch of bacteria before a holiday, and the bacteria were weakened by prolonged oxygen exposure.

What is an adjuvant and when were they first discovered?

An adjuvant is a substance that helps increase the effectiveness of a vaccine. They were first discovered in 1926 when aluminum salts were found to enhance the diphtheria toxoid.

What are the two main types of vaccines mentioned in the script?

The two main types of vaccines mentioned are live attenuated vaccines, which contain weakened live virus, and inactivated vaccines, which are killed with heat or chemicals.

What is the risk associated with live attenuated vaccines?

The risk with live attenuated vaccines is that they could potentially revert to the original disease-causing form, although this is known to happen only with the live oral polio vaccine.

How do toxoid vaccines work?

Toxoid vaccines target the toxin produced by a disease-causing germ. They are used to vaccinate against diseases like diphtheria and tetanus.

What is a subunit vaccine and when was the first one licensed?

A subunit vaccine includes only the components of a pathogen that stimulate the immune system. The first subunit viral vaccine for hepatitis B was licensed in 1981.

What is recombinant DNA technology in the context of vaccine production?

Recombinant DNA technology involves joining DNA molecules from two different species to produce a vaccine. The first vaccine based on this technology was a hepatitis B vaccine licensed in 1986.

What is a conjugate vaccine and how does it differ from a pure polysaccharide vaccine?

A conjugate vaccine links polysaccharides to a carrier protein to create a stronger immune response, including in children. Pure polysaccharide vaccines are less effective in children under two and lack a booster response upon repeated doses.

What is the modern miracle attributed to vaccines?

Vaccines are considered a modern miracle because they have led to the eradication of smallpox and near-eradication of wild poliovirus, as well as significantly reducing the impact of many other diseases.

Outlines

00:00

💉 The Evolution of Vaccines

This paragraph delves into the history and development of vaccines. It starts with the first vaccinations in the late 1700s using cowpox material to induce immunity against smallpox. The narrative then moves to the first laboratory-developed vaccine in 1879 by Louis Pasteur, who discovered the concept of weakening pathogens to create vaccines. The paragraph explores various methods of vaccine creation, including the use of aluminum salts as adjuvants to enhance vaccine effectiveness. It distinguishes between live attenuated and inactivated vaccines, explaining the processes and implications of each. The paragraph also touches on the use of cell cultures, such as chick embryos and human cells, in vaccine production, and the advent of combined vaccines like the DTaP. The development of the polio vaccine by Jonas Salk and the hepatitis B subunit vaccine are also highlighted, emphasizing the ongoing innovation in vaccine technology.

05:01

🧬 Advances in Vaccine Technology

The second paragraph focuses on more recent advancements in vaccine technology. It discusses the creation of the first vaccine based on recombinant DNA technology, which involves joining DNA molecules from different species to produce a vaccine. This technology was used to develop a hepatitis B vaccine that did not require human serum, making it safer and more effective. The paragraph also explains the concept of conjugate vaccines, which improve the immune response, especially in young children, by linking polysaccharides to a carrier protein. The paragraph concludes by emphasizing the continuous innovation in vaccine development and the importance of vaccines in eradicating diseases like smallpox and polio. It also hints at upcoming discussions on the immune system's response to vaccines and the concept of herd immunity.

Keywords

💡Vaccination

Vaccination refers to the process of introducing a vaccine into the body to produce immunity to a specific disease. It is the central theme of the video, which discusses the history and development of vaccines. For instance, the video mentions the first vaccinations using cowpox material to induce immunity against smallpox.

💡Inoculation

Inoculation is an older term related to vaccination, referring to the deliberate introduction of a disease agent into an individual to provide immunity. The video script discusses variolation as a precursor to vaccination, which involved using small amounts of the smallpox virus to induce immunity.

💡Live Attenuated Vaccines

Live attenuated vaccines are made from live viruses that have been weakened so they do not cause serious illness but can still induce immunity. The video explains that these vaccines can revert to their original form, as seen with the live oral polio vaccine.

💡Inactivated Vaccines

Inactivated vaccines contain viruses or bacteria that have been killed or inactivated, so they cannot replicate. The video mentions that these vaccines often require multiple doses and boosters because they do not mimic natural infection as closely as live virus vaccines do.

💡Adjuvants

Adjuvants are substances used in vaccines to enhance the body's immune response. The video notes that aluminum salts were discovered in 1926 to increase the effectiveness of the diphtheria toxoid, and adjuvants are now regularly used in vaccines.

💡Toxoid Vaccines

Toxoid vaccines are designed to target the toxin produced by a disease-causing germ. The video uses diphtheria and tetanus as examples, where the vaccines are used to protect against diseases caused by these toxins.

💡Subunit and Conjugate Vaccines

Subunit vaccines include only the components of a pathogen that stimulate the immune system, while conjugate vaccines link these subunits to a carrier protein to enhance the immune response. The video mentions the hepatitis B vaccine as an example of a subunit vaccine and explains how conjugate vaccines overcome the limitations of pure polysaccharide vaccines in children.

💡Recombinant DNA Technology

Recombinant DNA technology is a method used to create vaccines by joining DNA molecules from different species. The video explains how this technology was used to create the hepatitis B vaccine by altering yeast cells to produce a virus antigen.

💡Viral Cultivation

Viral cultivation refers to the process of growing viruses in a laboratory for vaccine development. The video discusses the historical shift from using live animals to cultivating viruses in cell lines, such as chick embryos or human cells, to reduce side effects and ethical concerns.

💡Combined Vaccines

Combined vaccines are formulations that protect against multiple diseases in a single vaccine. The video mentions the first combined vaccine available in the United States in 1948, which combined diphtheria, tetanus, and pertussis vaccines.

💡Viral Eradication

Viral eradication is the complete elimination of a virus from the human population. The video highlights the success of vaccines in eradicating smallpox and nearly eradicating polio, emphasizing the importance of vaccination in controlling disease.

Highlights

The history of vaccination began in the late 1700s with the use of cowpox material for smallpox immunity.

The first laboratory-developed vaccine was created in 1879 by Louis Pasteur for cholera.

Pasteur's discovery of vaccine development was accidental due to his assistant's delay in injecting chickens with fresh bacteria.

The weakened bacteria due to oxygen exposure served as a less deadly but effective antigen.

Other lab-based vaccine advancements included the use of carbolic acid, drying of infected tissue, heat treatment, and formalin.

In 1926, aluminum salts were found to increase the effectiveness of the diphtheria toxoid, now known as adjuvants.

Live attenuated vaccines contain weakened live viruses to induce immunity without causing serious illness.

Inactivated vaccines are not alive and cannot replicate, requiring multiple doses and boosters.

Toxoid vaccines target the toxin produced by disease-causing germs, used for diseases like diphtheria and tetanus.

Subunit and conjugate vaccines were mentioned as a topic for later discussion.

Vaccines like rabies and polio were cultivated in chick embryos to avoid side effects.

The use of human cells in vaccine production began around the 1960s following the detection of simian virus.

The first combined vaccine for diphtheria, tetanus, and pertussis was available in the U.S. in 1948.

Jonas Salk began human trials with the killed poliovirus vaccine in 1952.

The hepatitis B subunit vaccine in 1981 was the first to include only components of a pathogen that stimulate the immune system.

The first vaccine based on recombinant DNA technology was the hepatitis B vaccine licensed in 1986.

Conjugate Hib vaccine in 1987 linked polysaccharides to a carrier protein for a stronger immune response.

Vaccine innovation continues with ongoing work to create new and better vaccines.

Smallpox was eradicated worldwide by 1980, and wild poliovirus is nearly eradicated.

Vaccination has significantly reduced the impact of many diseases that once caused widespread suffering.

Transcripts

thanks in part to support from the

national institute for healthcare

management foundation

we're spending six episodes on a special

series on vaccines

last week we discussed the history of

inoculation specifically

varialation as a precursor for

vaccination

the history of vaccination is the topic

of this week's health care triage

[Music]

last week we ended with the world's

first vaccinations in the late 1700s

when cowpox material was used to induce

smallpox immunity

after this it was quite a while before

any new vaccines appeared on the scenes

we saw the first

laboratory developed vaccine in 1879

when louis pasteur weakened cholera

bacteria

in the laboratory for use in an

immunization he accidentally discovered

that this was possible

when his assistant forgot to inject

chickens with a fresh batch of bacteria

before a holiday

injecting the chickens instead when he

returned a month later

these chickens survived showing to only

mild symptoms

and later proved to be immune to further

infection pasteur figured out that the

bacteria had been weakened by the

prolonged oxygen exposure

thus creating a less deadly but still

effective antigen

other lab-based vaccine advancements

followed including

the weakening of anthrax bacteria with

carbolic acid

weakening of rabies virus via the drying

of infected nervous system tissue

from rabbits weakening of diphtheria

toxin

and cholera bacteria by heat treatment

and weakening of a measles virus strain

by passing it several times like

40 to 80 times through different cell

types these

and other methods including the use of

formalin a solution of formaldehyde

were experimented with to kill or weaken

viruses toxins and bacteria

in order to create safe and effective

vaccines

in 1926 it was discovered that aluminum

salts could help to increase the

effectiveness of the diphtheria toxoid

we now call such substances adjuvants

and make regular use of them

it might be good to stop here and

explain the different types of vaccines

we'll start with live attenuated and

inactivated vaccines

live attenuated vaccines are made by

weakening the disease-causing virus

meaning it contains live virus to induce

immunity

but in a form that cannot cause serious

illness

we should note that these types of

vaccines could revert to the original

disease causing form

though this is only known to happen with

the live

oral polio vaccine the polio shot

not a live virus inactivated viruses

have been

inactivated with heat or chemicals like

formalin

and are thus not alive and able to

replicate

the response to these vaccines doesn't

resemble natural infection in the way

that live virus responses do

and they often require multiple doses

and then boosters

despite these limitations inactivated

viruses are sometimes necessary

due to limitations of live vaccines such

as their storage temperature needs or

the risk of

live virus exposure in cases of a

weakened immune system there are also

toxoid vaccines which target the toxin

produced by a disease-causing germ

toxoid vaccines are used to vaccinate

against diseases like diphtheria

and tetanus and lastly there are also

subunit

and conjugate vaccines which we'll get

to in a bit production techniques have

also undergone enormous changes over the

years

it was discovered that viruses like

rabies and polio that affect the nervous

system could be cultivated in chick

embryos

which help to avoid major side effects

that result from cultivating a virus

with nervous system tissue

a method was also developed to cultivate

poliovirus and monkey kidney cells

and other viruses in dog and rabbit

kidney cells and in duck embryos

these discoveries also help to reduce

our reliance on using

live animals like monkeys for growing

and testing viruses

however researchers began shifting to

the use of human cells around the 1960s

following the detection of simian virus

and monkey kidney cells

which prompted some concerns though

later research found no relationship

between the presence of that virus

and vaccine complications this does mean

that many vaccines involve the use of

cell lines derived from human fetal

cells

which is a complex and controversial

topic one that would take an

entire episode if not series all on its

own

in 1948 the first combined vaccine

became available in the united states

it combined the diphtheria tetanus and

pertussis vaccines

in 1952 jonas salk began the first human

trials with the killed poliovirus

vaccine

the vaccine was licensed by the us

government when results were announced

in 1955

with 80 to 90 effectiveness against

paralytic polio

1981 we saw the first subunit viral

vaccine for hepatitis b

subunit vaccines include only the

components of a pathogen that stimulate

the immune system

as opposed to including the entire

pathogen these vaccines often require

the use of those

adjuvants i mentioned earlier since they

aren't generally strong enough on their

own

all hpv vaccines licensed in the u.s are

subunit vaccines

using a protein that self-assembles to

form empty shells

that resemble hpv virus-like proteins

and in 1986 a hepatitis b vaccine that

did not use human serum became the first

vaccine based on recombinant dna

technology

which describes the process of joining

dna molecules

from two different species together this

sounds pretty frankenstein

and has thus sometimes been used to

scare people but it's actually pretty

straightforward once you understand what

the process actually entails and

achieves

for this vaccine the process involved

altering yeast cells

so that they produce the viruses antigen

the component of the virus that elicits

an immune response

which in this case was a surface protein

in the virus

this was done by using an enzyme to

remove the surface protein

and then insert the code for that

protein into yeast cells

so they could grow a bunch of it in

order to manufacture the vaccines

it's an incredible feat of technology

it's also safe and effective

in 1987 a conjugate hib vaccine

as opposed to pure polysaccharide

vaccine was licensed

polysaccharides are long chains of sugar

molecules that create an

outer coating on the antigens of certain

bacteria pure polysaccharide vaccines

are able to induce antibodies against

these but

aren't all that effective in children

younger than two because their immature

immune system struggles to recognize the

coded antigens

these vaccines also lack a booster

response upon repeated doses

these issues were resolved with the

development of conjugate vaccines

which linked the polysaccharides to a

carrier protein

an alteration that resulted in a

stronger immune response

including a response in children though

we should note that there are still pure

polysaccharide vaccines available for a

small group of diseases

we could go on and on for days about all

the individual developments advancements

trials and people that have contributed

to vaccines as we know them

but we've done our best to cover the

larger steps as concisely as we could

and we should mention that vaccine

innovation isn't a thing of the past

work is still underway to create new and

better vaccines

for now we'd just like to stress what a

modern miracle the vaccine is

the last cases of naturally occurring

smallpox in the united states happened

in texas in 1949

and no cases of naturally occurring

smallpox have been seen in the world

since 1980.

wild poliovirus is very nearly

eradicated

and many diseases that used to wreak

havoc on the human race have been

brought to heal by vaccination

it's truly a shame the vaccines are

sometimes villainized more than the

horrible diseases they protect us from

next week in the third episode of this

series we'll talk about the landscape in

which the vaccine thrives

the immune system how does it work and

how does it respond to viruses and

vaccines

what's the deal with vaccines and herd

immunity these questions and more

next week we hope to see you there hey

you enjoyed this episode you should

enjoy episode one in the series on the

history of inoculation

you should also watch the playlist of

the whole series we'd also like if you

like the video and subscribe to the

channel down below so you don't miss

anything

and also go on over to patreon.com

healthcare triage where you can help

support the show even during a global

pandemic

we'd like to especially acknowledge our

research associates james glasgow joe

severts josh gister and michael chin

and of course our surgeon admiral sam