Hepatitis B vaccine
Based on Wikipedia: Hepatitis B vaccine
In the late 1970s, Maurice Hilleman faced an unusual problem. He had figured out how to make a vaccine against hepatitis B—a virus that silently destroys livers and kills hundreds of thousands of people each year—but his solution required collecting blood from gay men and intravenous drug users. This was years before anyone knew HIV existed. The blood samples he gathered almost certainly contained the virus that would soon devastate these same communities.
Hilleman's vaccine worked. And remarkably, his purification process was so thorough that it killed every virus in those blood samples, including the one nobody knew to look for.
This story captures something essential about the hepatitis B vaccine: it has always been at the cutting edge of what's medically possible, sometimes in ways its creators didn't fully understand at the time.
Why Hepatitis B Matters
Hepatitis B is a stealth killer. The virus attacks the liver, and in adults, the immune system usually clears it within a few months. Unpleasant, but survivable. Infants are different.
When a baby contracts hepatitis B, the outcome flips dramatically. Ninety percent of infected infants who don't receive the vaccine will develop chronic infection. That word "chronic" sounds almost benign—like a bad back or seasonal allergies. It isn't. Chronic hepatitis B means the virus never leaves. It sits in the liver for decades, slowly causing scarring, cirrhosis, and eventually, in fifteen to twenty-five percent of cases, death from liver cancer or liver failure.
This is why the hepatitis B vaccine is recommended within twenty-four hours of birth. Not at the two-month checkup. Not when the child starts daycare. Within the first day of life. The virus spreads through blood and bodily fluids, and a mother with hepatitis B can easily transmit it during childbirth. The vaccine, given immediately, can prevent a lifetime of chronic disease.
The Discovery of a Hidden Enemy
The story begins in 1963, in a laboratory at the Fox Chase Cancer Center in Philadelphia. Baruch Blumberg, a physician and geneticist, was studying genetic variations in blood proteins across different human populations. He was looking at blood samples from people around the world when he noticed something strange in a sample from an Australian Aboriginal person.
He called it the "Australia Antigen."
An antigen is simply any molecule that the immune system recognizes as foreign—something that triggers the body to produce antibodies. Blumberg had found a new protein floating in human blood, but he didn't know what it was or where it came from.
Five years later, in 1968, virologist Alfred Prince made the connection. The Australia Antigen was actually part of a virus—specifically, the outer coating of the hepatitis B virus. When the virus infects liver cells, it produces far more of these surface proteins than it needs, and the excess spills into the bloodstream. Blumberg had accidentally discovered the viral fingerprint of a disease that had been killing people for millennia.
In 1976, Blumberg won the Nobel Prize in Physiology or Medicine. But he didn't stop at discovery. He realized that if the immune system could recognize these surface proteins as foreign invaders, then perhaps injecting just the proteins—without any actual virus—could train the body to fight off future infections.
A Vaccine Made from Blood
Blumberg's insight led to an unconventional approach. Most vaccines at the time were made by weakening or killing whole viruses, then injecting them to provoke an immune response. Blumberg proposed something different: skip the virus entirely and just use the surface proteins.
The problem was obtaining enough of these proteins. They couldn't be grown in a laboratory. They could only be found in one place: the blood of people chronically infected with hepatitis B.
Maurice Hilleman, who led vaccine development at Merck, took on the challenge. He knew exactly where to find high concentrations of hepatitis B: in communities where the virus spread easily through blood contact. In the late 1970s, that meant gay men and intravenous drug users.
Hilleman developed a rigorous purification process. The blood was treated with pepsin (a digestive enzyme), urea (which unfolds and destroys proteins), and formaldehyde (which kills microorganisms). Then it was filtered repeatedly. The goal was to extract only the hepatitis B surface proteins while destroying absolutely everything else.
The process worked better than anyone knew. When HIV emerged a few years later, researchers went back and tested the blood-derived vaccines. They were clean. Hilleman's purification had killed a virus that hadn't even been discovered yet.
The first blood-derived hepatitis B vaccine, called Heptavax-B, was approved in the United States in 1981. The large-scale trials had been conducted primarily on gay men in New York City, and the results, published by Wolf Szmuness and colleagues, showed strong protection against the virus.
The Recombinant Revolution
Despite its effectiveness, the blood-derived vaccine had problems. Collecting blood from infected donors was expensive and logistically difficult. And as the AIDS epidemic exploded in the early 1980s, a vaccine made from blood—especially blood from high-risk populations—became increasingly difficult to sell to a frightened public.
Some people falsely blamed the hepatitis B vaccine for spreading AIDS. This was wrong—the purification process had eliminated HIV—but the perception lingered.
Hilleman and his team at Merck were already working on a solution. Rather than extracting surface proteins from human blood, what if they could get something else to manufacture those proteins?
They turned to yeast.
Scientists inserted the gene for the hepatitis B surface protein into ordinary baker's yeast—Saccharomyces cerevisiae, the same organism that makes bread rise and beer ferment. The yeast read the inserted gene and obediently produced hepatitis B surface proteins, pumping them out like a tiny biological factory.
This was revolutionary. For the first time, a human vaccine was being produced through recombinant DNA technology. There was no human blood involved, no risk of contamination with unknown pathogens, and virtually unlimited production capacity. Yeast is cheap to grow.
The recombinant vaccine, called Recombivax HB, was approved by the Food and Drug Administration on July 23, 1986. The blood-derived vaccine was withdrawn from the market the same year. For this work, Merck collaborated with researchers at the University of California, San Francisco, and the University of Washington. Some of those researchers, including William Rutter, Pablo Valenzuela, and Edward Penhoet, went on to co-found Chiron Corporation, which became a major vaccine manufacturer.
How the Vaccine Works
The mechanics of the hepatitis B vaccine are elegant in their simplicity.
When you receive the vaccine, you're injected with hepatitis B surface proteins—either purified from blood (in the original version) or manufactured by yeast (in the modern version). These proteins cannot cause infection because there's no viral DNA inside them. They're just empty shells, harmless fragments that look exactly like the real virus on the outside.
Your immune system doesn't know the difference. It sees these foreign proteins, sounds the alarm, and begins manufacturing antibodies specifically shaped to bind to hepatitis B surface proteins. The process takes a few weeks, but once complete, your immune system has essentially created a lock that fits only one key.
If you're later exposed to actual hepatitis B virus, those antibodies recognize the surface proteins immediately. They bind to the virus and flag it for destruction before it can infect your liver cells. The battle is over before it begins.
The vaccine also trains immune memory cells—long-lived sentinels that remember the hepatitis B surface protein for decades. Even if your circulating antibody levels drop below detectable levels, these memory cells remain. Studies have shown that immune memory persists for at least thirty years, and probably indefinitely. When someone who was vaccinated long ago encounters hepatitis B, their immune system can rapidly ramp up antibody production through what immunologists call an "anamnestic response"—essentially, the body remembering an old enemy and reacting swiftly.
This is why most people don't need booster shots after the initial vaccination series. The protection is essentially lifelong.
The Vaccination Schedule
For healthy infants, the standard schedule involves three or four doses. The first dose is given within twenty-four hours of birth. The second dose comes at one to two months of age. The third dose is given between six and eighteen months.
This timing isn't arbitrary. The first dose, given immediately after birth, is crucial for babies whose mothers have hepatitis B. Without it, the virus can establish chronic infection in the critical first days of life. The subsequent doses reinforce the immune response, building up a strong, lasting protection.
For infants born to mothers who test positive for hepatitis B surface antigen, or whose status is unknown, doctors add an extra layer of protection: hepatitis B immune globulin, given alongside the vaccine. This is essentially a dose of pre-made antibodies, harvested from people who are already immune. It provides immediate protection while the baby's own immune system learns to produce its own antibodies.
The combination of vaccine plus immune globulin is remarkably effective at preventing mother-to-child transmission—better than either approach alone.
Effectiveness and Response Rates
In healthy people, the hepatitis B vaccine works extraordinarily well. More than ninety-five percent of people who complete the vaccination series develop protective immunity.
Doctors measure this by checking antibody levels in the blood. An antibody level above 100 milli-international units per milliliter is considered excellent protection. Levels between 10 and 100 milli-international units per milliliter indicate a weaker response—these people might benefit from a single booster shot. Levels below 10 indicate the vaccine didn't work.
For most people, there's no need to test antibody levels after vaccination. The vaccine works reliably, and checking everyone's blood would be wasteful. But certain groups do need testing: healthcare workers who might be exposed to infected blood, people with HIV or other conditions that weaken the immune system, dialysis patients, organ transplant recipients, and sexual partners of people with hepatitis B.
What happens if someone doesn't respond to the vaccine? First, doctors check whether the person might already have hepatitis B—current infection or past infection that cleared on its own. If not, they administer another complete series of three doses. About half of initial non-responders will develop immunity after this second series.
For the stubborn cases who still don't respond, there are options: higher doses, intradermal injection (into the skin rather than muscle), or combination vaccines that include hepatitis A. And for those who never develop immunity, there's hepatitis B immune globulin—passive protection that can be given after exposure to the virus.
Who Responds Poorly?
Certain factors predict a weaker response to the vaccine. Age matters: people over forty respond less robustly than younger adults. Obesity reduces vaccine effectiveness, as does smoking. Alcoholics, especially those with liver disease, often struggle to mount a good immune response—which is tragically ironic, since their damaged livers are especially vulnerable to hepatitis B.
People with celiac disease, an autoimmune condition affecting the intestines, sometimes respond poorly. So do people with HIV, those on dialysis, and anyone taking immunosuppressive medications. These groups may need larger doses or more frequent vaccinations.
There's also an intriguing connection to parasitic infections. Helminthiasis—infection with parasitic worms—can impair the immune response to the hepatitis B vaccine. This matters in tropical countries where both parasites and hepatitis B are common.
Safety Profile
Serious side effects from the hepatitis B vaccine are exceptionally rare. The most common complaint is pain at the injection site—the same mild soreness that follows many vaccinations.
The vaccine is considered safe during pregnancy and breastfeeding. It has not been linked to Guillain-Barré syndrome, a rare nerve disorder sometimes associated with other vaccines.
Perhaps the most persistent safety controversy involved multiple sclerosis. In the 1990s and 2000s, some studies suggested a possible link between hepatitis B vaccination and multiple sclerosis or other demyelinating diseases (conditions where the immune system attacks the protective coating around nerve fibers). A 2004 study reported an increased risk within three years of vaccination.
This finding was controversial. Other researchers criticized the study's methodology, and subsequent investigations failed to confirm the association. A 2006 review concluded that evidence did not support a link between hepatitis B vaccination and chronic fatigue syndrome, sudden infant death syndrome, or multiple sclerosis. A 2007 study specifically examined children and found no increased risk of a first multiple sclerosis episode after vaccination.
The current scientific consensus is that the hepatitis B vaccine does not cause multiple sclerosis or other autoimmune diseases. But the controversy had real-world consequences: hepatitis B vaccination rates in children remained low in several countries for years, leaving children vulnerable to a genuinely dangerous virus.
Global Impact
The hepatitis B vaccine has achieved something remarkable: it prevents cancer.
Taiwan provides the clearest evidence. In 1984, the country implemented a nationwide hepatitis B vaccination program for all newborns. Researchers tracked what happened next. Childhood hepatocellular carcinoma—liver cancer—declined dramatically. By vaccinating babies against a virus, Taiwan had reduced rates of a cancer that wouldn't have appeared until years or decades later.
This makes the hepatitis B vaccine one of the first successful cancer vaccines, though it works indirectly. It doesn't attack cancer cells. Instead, it prevents the chronic infection that would eventually cause cancer.
The World Health Organization now recommends hepatitis B vaccination as part of routine childhood immunization worldwide. Many countries use a pentavalent vaccine—a single shot that protects against five diseases: diphtheria, tetanus, pertussis (whooping cough), Haemophilus influenzae type B (a bacterium that causes meningitis and pneumonia), and hepatitis B.
Vaccination rates vary enormously by country. In developed nations, coverage often exceeds ninety percent. In some developing countries, rates remain much lower, leaving millions of children at risk for chronic infection and, eventually, liver disease.
Vaccination in Adults
While infant vaccination is the most important strategy for eliminating hepatitis B, adults also benefit from immunization—especially those in high-risk groups.
Healthcare workers are a priority. Anyone who might be exposed to blood or bodily fluids should be vaccinated. This includes doctors, nurses, lab technicians, emergency responders, and anyone who handles needles or works in dialysis centers. In many countries, hepatitis B vaccination is mandatory for healthcare and laboratory staff.
Other high-risk groups include people with multiple sexual partners, men who have sex with men, injection drug users, people with chronic liver disease, travelers to regions where hepatitis B is common, and household contacts of people with chronic infection.
The United States Centers for Disease Control and Prevention also recommends vaccination for people with diabetes, who face elevated risks from blood glucose monitoring and insulin injections.
Despite these recommendations, adult vaccination rates lag far behind infant rates. According to CDC data, only about thirty-four percent of American adults over eighteen have received at least one dose of hepatitis B vaccine. Coverage varies by demographics: Asian adults have the highest rates, followed by white adults, with lower rates among Black and Hispanic adults.
Travel matters too. Adults who travel internationally have vaccination rates around forty-three percent, compared to less than thirty percent for non-travelers.
Newer Vaccines
The basic recombinant hepatitis B vaccine has been in use since 1986, but improvements continue.
In 2017, the FDA approved Heplisav-B, a two-dose vaccine for adults. Most hepatitis B vaccines require three doses over six months; Heplisav-B achieves similar protection with just two doses over one month. It uses a novel adjuvant—a substance that boosts the immune response—called CpG 1018, which consists of short synthetic DNA sequences that activate immune cells.
In 2021, the FDA approved Prehevbrio, another recombinant hepatitis B vaccine for adults.
Combination vaccines continue to expand. The Advisory Committee on Immunization Practices recommends a pentavalent vaccine for infants that combines protection against diphtheria, tetanus, pertussis, hepatitis B, and polio in a single shot. Fewer injections mean better compliance and less crying.
The Bigger Picture
The hepatitis B vaccine represents a triumph of medical science that most people never think about. A virus that once condemned millions to chronic disease and early death can now be prevented with a few painless injections in infancy.
Maurice Hilleman, who developed both the blood-derived and recombinant versions, is estimated to have saved more lives than any other medical scientist in history. Beyond hepatitis B, he developed vaccines against measles, mumps, rubella, chickenpox, meningitis, and pneumonia. He worked at Merck until his death in 2005 at age eighty-five, rarely receiving the public recognition given to other medical pioneers.
Baruch Blumberg, who discovered the Australia Antigen that made everything possible, died in 2011. His accidental discovery in 1963—a strange protein in the blood of an Australian Aboriginal person—set in motion a chain of research that would prevent millions of cases of chronic liver disease and liver cancer.
Today, the hepatitis B vaccine remains on the World Health Organization's List of Essential Medicines. It is given to newborns in hospitals around the world, often before they leave the birth suite. For most of these babies, it's the beginning of a lifetime of protection against a virus their great-grandparents feared but couldn't name.
The debates continue—about vaccination schedules, about combination vaccines, about reaching underserved populations, about convincing skeptical adults to get immunized. But the fundamental science is settled. The hepatitis B vaccine works, it's safe, and it prevents not just infection but cancer. Few medical interventions can make that claim.