Thread by @ebtapper

The hepatitis B vaccine is amazing.

It also has a wild backstory
Want to hear it?

A #tweetorial

1/

#livertwitter #MedTwitter

First:

Hepatitis B sucks
1⃣About 3-4 in every 100 people have it
2⃣It causes liver cancer, #cirrhosis

But the vaccine rocks!
1⃣Prevents liver cancer!
2⃣Was first recombinant vaccine!

So let's get into it

2/

Did you know that the discovery of hepatitis B was recognized with the 1976 @NobelPrize for Dr. Baruch Blumberg?

His studies over the course of 5 years 1964-1969 changed the world.

Let's take a look

3/

Hep B discovery

1⃣Looking for new blood antigens, Blumberg finds a weird one. It reacts with an 🇦🇺man's serum
2⃣The '🇦🇺antigen' is found in people with leukemia, hemophilia, & living in institutions (e.g. Down's)
3⃣🇦🇺antigen pops up during viral hepatitis

4/

Why did Blumberg even think that 🇦🇺 antigen (hepatitis B) could cause hepatitis?

A technician working in his lab - Dr. Barbara Werner - got sick with jaundice and hepatitis. She tested herself for Australia antigen...and it was positive. She recovered. Rest is history
5/

Funny thing about hep B

1⃣Multiple hep B particles are found in the blood
2⃣One - surface (🇦🇺) antigen - exceeds the other - core antigen - by 100,000:1
3⃣The surface (🇦🇺) antigen alone is NOT infectious!

6/

Why can we see surface antigen separate from the infectious viral particles (surface coating the core) in the blood of people with hepatitis B?

This has to do with how HBV DNA is transcribed in the liver cell. The parts get made separately and then assembled.

7/

But WHY would there be massive surface antigen overproduction relative to the other parts of the virus?

Only hep B knows!

It is thought that this influences our immune system in a way that is advantageous for the virus

But we can fight back!
Next slide please

8/

An idea is born:
If hep b makes a ton of surface antigen, we can separate it from the infectious parts and use it to generate an antibody against the virus

Blumberg develops the method to purify surface antigen from infected plasma and files a patent in 1969

9/

But are antibodies against surface antigen protective against infection?

In this study of patients receiving dialysis - where there was a crazy high rate of hep B infections - it sure looked like having antibodies against surface antigen was good

10/

Now if we gave surface antigen injections, would we make antibodies? And would antibodies prevent infection with hep B?

In 1976, chimpanzees were enrolled in 'challenge trials' - some were given a surface antigen injection before being infected. It worked!

11/

So where are we getting all of this surface antigen from?

We are getting it from volunteers with hep B who donated their plasma!

BONUS: Not only can we get antigen from infected people, we can get antibody from exposed people!

12/

Looks like we have 2 tools in the box
1⃣Antibody (HBIG, hepatitis B immune globulin)
2⃣Antigen (to train our body to make antibody)

HBIG is best for clear exposure like, say, a baby on their birthday when mom has HBV

RCT: HBIG works great at birth, 3, and 6 months

13/

Between 1980-1982 the world would see the results of a plasma-derived hepatitis B vaccine

These trials showed that the vaccine was >90% effective, >98% if 3 doses were given and the patient made surface antibodies

Game. changed.

14/

Hold up!

Despite the success of the plasma-derived vaccine, the 80's brought awareness that plasma could transmit viruses like HIV, even with safety precautions

Enter the mighty yeast!
1⃣Yeast can make surface antigen
2⃣It's effective as vax in trial of chimps
PHEW!
/15

The recombinant vaccine made in yeast was proven to be just as effective as the plasma vaccine, even for newborns!

And it has CRUSHED Hep B and liver cancer. See Figure 3 from Taiwan

/16

SUMMARY

1⃣HBV causes liver cancer, #cirrhosis
2⃣HBV has a non-infectious surface antigen which is made 100000x more than the infectious core. We use antigen for the vax
3⃣HBV vaccine was 1st recombinant DNA vax. Made by yeast
4⃣HBV vax has⬇️liver cancer

/17

This concludes a #tweetorial on the HBV vaccine. I hope you enjoyed the story of HBV discovery and its super effective, cancer preventing vaccine. I would like to thank my boss, mentor, and Queen of HBV, Dr. Anna Lok for her peer review and contributions.

/end

Here is a picture of Blumberg (who discovered Hep B) and Dr. Lok, on the occasion of her Distinguished Scientist Award from @HepBFoundation. Also, inscription from Blumberg to Lok inside his memoir.

The anti-HBV force in that picture is off the charts