Tag: antigens

How Are Vaccines Really Made?

Do you know how vaccines are made?

A lab worker injects flu virus into an egg, one of many steps in making our flu vaccines.
A lab worker injects flu virus into an egg, one of many steps in making our flu vaccines. Photo courtesy of the FDA

When we say that chickens are used to make flu vaccine, do you think that means that live chickens are actually infected with the flu to make the vaccine?

They aren’t.

Just like live monkeys aren’t injected with the polio virus to make the polio vaccine.

Those are just myths you see in vaccine scare videos on anti-vaccine websites.

How Are Vaccines Really Made?

So how are vaccines really made?

It depends, after all, there are a lot of different types of vaccines.

But instead of monkey cages and chicken coops in the labs of today’s vaccine manufacturers, you will find clean rooms with large scale, stainless steel bioreactors, master cell banks, seed fermenters, microcarriers, centrifuges, filtration and chromatography equipment, and filling and lyophilization equipment.

Do you picture a series of these large scale, stainless steel bioreactors when you think about how vaccines are made?
Do you picture a series of these large scale, stainless steel bioreactors when you think about how vaccines are made?

That doesn’t sound so scary or shocking, does it?

What’s shocking about the whole process of making a vaccine?

It takes a long time. Often one to three years! And that’s after all of the time that went into the research, testing, and licensing of the vaccine.

“Viruses are grown in cells, which can be either primary cells, such as chicken fbroblasts (e.g., yellow fever vaccine), or continuous cell lines, such as MRC-5 (e.g., hepatitis A vaccine). Bacterial pathogens are grown in bioreactors using medium developed to optimize the yield of the antigen while maintaining its integrity. Recombinant proteins can be manufactured in bacteria, yeast, or cell culture. ”

Plotkin’s Vaccines (Seventh Edition)

The only other shocking thing about making vaccines is how boring it all is, at least if you aren’t into biology, with most vaccines using the same basic steps:

  • decide on the type of antigen – vaccines can be made of attenuated live viruses, inactivated viruses or bacteria,  or just part of the virus or bacteria (subunit and conjugate vaccines)
  • generate an antigen – this is the thing in the vaccine that will stimulate an immune response and protect your child. It used to be what anti-vaccine folks were concerned about until we explained that kids today are exposed to far fewer antigens, even though they get more vaccines and more protection.
  • release and isolate the antigen – the antigen was either growing in cells or other medium and in this step, as much of the antigen is collected as possible.
  • purify the antigen – multiple steps are involved in removing many of the vaccine ingredients or excipients that were used up to this step by precipitation, ultrafiltration, and column chromatography, etc. That’s why many are said to remain only in residual amounts, like formaldehyde.
  • strengthen the antigen – in this step, an adjuvant might be added.
  • combine all of the ingredientsstabilizers and preservatives might also be added in this step.
  • last steps – finished vaccine is put in vials and syringes and then packaged
  • lot release and distribution – each lot is tested before it is released to make sure it meets FDA standards for potency, safety, and sterility.

None of that sounds as scary as injecting monkeys with smallpox, watching them die, and then harvesting their infected kidney cells though, does it? If you have watched any of the anti-vaccine scare videos, hopefully the first thing that came to mind is that the smallpox vaccine isn’t actually made with the smallpox virus! It is, of course, made with vaccinia virus and wouldn’t cause anyone, whether a monkey, cow, or person to actually get smallpox. And if you haven’t figured it out by now, monkeys aren’t used to make smallpox vaccines.

“Both vaccines are derived from the New York City Board of Health strain of vaccinia, but Dryvax was grown on the skin of calves and then essentially freeze-dried for storage. It was licensed by FDA in 1931 but is no longer manufactured. ACAM2000, a “second generation” smallpox vaccine, is derived from a clone of Dryvax, purified, and produced using modern cell culture technology.”

FDA on ACAM2000 (Smallpox Vaccine) Questions and Answers

In fact, most of today’s vaccines are made in bioreactors, not in cows or monkeys.

Flu vaccine is mostly still made using chicken eggs, specifically 11-day-old embryonated chicken eggs. The flu viruses are passed into the eggs, incubated for a time to allow them to grow, and then harvested, inactivated, and purified.

How purified do they get? So purified that even people with egg allergies can get a flu vaccine these days.

Vaccines are safe. Vaccines are made safely.

What to Know About How Vaccines Are Really Made

Vaccines are made using a very safe and scientific process that is heavily regulated that will neither scare nor shock you.

More on How Vaccines Are Really Made

Four Generations of Vaccines and Vaccine Preventable Diseases

This image that has been floating around the Internets conveys a lot of information, both about vaccines and vaccine-preventable diseases. And about the propaganda being pushed by the anti-vaccine movement.

Four generations of vaccines or vaccine misinformation?
Four generations of vaccines or vaccine misinformation?

A lot has changed over the last four generations…

Four Generations of Vaccine Preventable Diseases

In the United States, we have seen:

  • 1949 – the last smallpox outbreak
  • 1970s – the last outbreak of respiratory diphtheria
  • 1979 – endemic polio was declared eliminated
  • 1979 – smallpox was declared eradicated
  • 2000 – endemic measles was declared eliminated
  • 2000- neonatal tetanus was declared eliminated
  • 2004 – endemic rubella and congenital rubella syndrome were declared eliminated
  • 2009 – endemic respiratory diphtheria was declared eliminated

But there hasn’t been as much change as some folks think.

Four Generations of Vaccines

For one thing, kids don’t get 69 vaccines today as part of the recommended immunization schedule.

We don’t even have 69 vaccines available to give children today!

And while 200+ vaccines are being tested or are in the “pipeline,” very few will end up on the childhood immunization schedule. For example, many of these are therapeutic vaccines to treat cancer, allergies, and other conditions. And a lot of the other pipeline vaccines are for the same infectious disease, including 36 vaccines being tested to prevent or treat HIV and 25 to prevent the flu.

So how many vaccines do kids actually get?

Kids today routinely get 13 vaccines to protect them from 16 vaccine-preventable diseases. More than 13 vaccines are available, but some aren’t used in the United States and some are only used in special situations or for high risk kids.

Also, looking at historical immunization schedules, it is clear that folks in the 1940s and 50s didn’t get just two vaccines.

schedule1940s
A schedule of immunizations from a 1948 AAP Round Table Discussion on the Practical and Immunological Aspects of Pediatric Immunizations

Did some kids really get annual tetanus and typhoid vaccine boosters back then?

It’s possible, after all, by the 1930s, we did have individual vaccines against diphtheria, tetanus, pertussis, typhoid, and smallpox.

This was followed by:

  • 1948 – the individual diphtheria, tetanus, and pertussis vaccines become combined in a single DTP vaccine
  • 1955 – first polio vaccine – IPV
  • 1962 – change to oral polio vaccine – OPV
  • 1963-68 – first measles vaccines
  • 1967 – first mumps vaccine
  • 1969 – first rubella vaccine
  • 1971 – the individual measles, mumps, and rubella vaccines become combined in a single MMR vaccine
  • 1972 – routine vaccination with smallpox vaccines end in the US

The next big change was the addition of the Hib vaccine to the schedule in 1985.

“…for those trained in pediatrics in the 1970s, Hib (Haemophilus influenzae type b) was a horror.”

Walter Orenstein, MD

This was followed in 1989, with the addition of the hepatitis B vaccine, expanded age ranges for Hib, and the start of the switch to DTaP.

By 2000, kids got protection against 11 vaccine-preventable diseases, and routinely got the DTaP, MMR, IPV, Hib, chicken pox, Prevnar, hepatitis B, and Td vaccines.

Over the years, vaccines and protection against rotavirus, hepatitis A, meningococcal bacteria, HPV, and a yearly flu shot were added to the schedule.

We still haven’t gotten to 69 vaccines though.

Looking at the latest immunization schedule from the CDC and AAP, it should be clear that kids don't get 69 vaccines.
Looking at the latest immunization schedule from the CDC and AAP, it should be clear that kids don’t get 69 vaccines.

Kids today do routinely get:

  • 13 vaccines, including DTaP, IPV (polio), hepatitis B, Hib, Prevnar 13, rotavirus, MMR, Varivax (chicken pox), hepatitis A, Tdap, HPV, MCV 4 (meningococcal vaccine), and influenza
  • protection against 16 vaccine-preventable diseases, including diphtheria, tetanus, pertussis, measles, mumps, rubella, polio, chicken pox, pneumococcal disease, hepatitis A, hepatitis B, meningococcal disease, HPV, rotavirus, Hib, and flu
  • about 28 doses of those vaccines by age two years
  • about 35 doses of those vaccines by age five years
  • as few as 23 individual shots by age five years if your child is getting combination vaccines, like Pediarix or Pentacel and Kinrix or Quadracel and Proquad
  • about 54 doses of those vaccines by age 18 years, with a third of that coming from yearly flu shots

How do you get a number like 69?

You can boost your count to make it look scarier by counting the DTaP, MMR, and Tdap vaccines as three separate vaccines each (even though they aren’t available as individual vaccines anymore). That quickly turns 8 shots into “24 vaccines.”

And that’s fine – as long as you are consistent. You can’t count them each as three vaccines today, but just as one when mom, grandma and great-grandma got them. If you are counting individual components of those vaccines, then great-grandma didn’t just get two vaccines, especially when you consider that she almost certainly would have gotten multiple doses of the DPT vaccine.

Paradoxically, even more antigens have been taken off the schedule with the removal of the smallpox and DPT vaccines. In 1960, kids got exposed to 3,217 different antigens from the smallpox, polio, diphtheria, tetanus and whole cell pertussis vaccines. All of today’s vaccines on the schedule expose them to just 177 different antigens!

Why does that matter? It is the antigens that are stimulating the immune system, so if you were really concerned about a number, that would be the one to look at.

More Vaccines Equal More Protection

Of course, the number of vaccines kids get and how they have increased over time is very important. But not in they way anti-vaccine folks like to think.

It is important because kids today are protected against and don’t have to worry about the consequences of many more life-threatening diseases, like bacterial meningitis (Hib and the pneumococcal bacteria), epiglottitis (Hib), liver failure and liver cancer (hepatitis B), severe dehydration (rotavirus), and cervical cancer (HPV), etc.

If you think kids get too many vaccines today, then you have no idea what things were like in the pre-vaccine era.

More on The Evolving Immunization Schedule

Myths About Your Baby’s Immature Immune System

Newborns and infants have immature immune systems, at least as compared to older children and adults.

Premature babies can usually get all vaccines on schedule - at their chronological age, not an adjusted age based on being a preemie.
Premature babies can usually get all vaccines on schedule – at their chronological age, not an adjusted age based on being a preemie. Photo by Vincent Iannelli, MD

That doesn’t mean that their immune system is so immature they they can’t fight off many infections or that they shouldn’t be vaccinated. Even premature babies should usually be vaccinated on time.

Your Baby’s Immature Immune System

So just how immature is their immune system?

“A picture emerges of a child born with an immature, innate and adaptive immune system, which matures and acquires memory as he or she grows.”

Simon et al on Evolution of the immune system in humans from infancy to old age

It is immature enough that the protection that they get from passive immunity and transplacental transfer of antibodies before they are born is considered critical to protect them from many infections.

“After birth, the sudden enormous exposure to environmental antigens, many of them derived from intestinal commensal bacteria, calls for a rapid change to make distinct immune responses appropriate for early life.”

Simon et al on Evolution of the immune system in humans from infancy to old age

Fortunately, their immune system quickly matures and develops, so that as their maternal protection begins to fade, they are “better armed with the maturing innate and adaptive immune systems.”

“The risks are now much reduced by vaccinations, which stimulate protective immune responses in the maturing immune system.”

Simon et al on Evolution of the immune system in humans from infancy to old age

Getting fully vaccinated  on time helps too.

Myths About Your Baby’s Immune Response to Vaccines

Getting vaccinated?

With an immature immune system?

How does that work?

It will likely come as a surprise to some folks, but it actually works quite well!

“Although infants can generate all functional T-cells (ie, Th1, Th2, and cytotoxic T-cells), infant B-cell responses are deficient when compared with older children and adults. Infants respond well to antigens (such as proteins) that require T-cell help for development. However, until about 2 years of age, the B-cell response to T-cell-independent antigens (such as polysaccharides) is considerably less than that found in adults.”

Offit et al on Addressing Parents’ Concerns: Do Multiple Vaccines Overwhelm or Weaken the Infant’s Immune System?

In fact, we know that:

  • newborns respond well to the birth dose of the hepatitis B vaccine
  • the birth dose of BCG vaccine is effective at preventing severe TB disease
  • infants respond well to the vaccines in the primary series that they get at 2, 4, and 6 months
  • while infants respond well to most vaccines, to “circumvent the infant’s inability to mount T-cell-independent B-cell responses,” we use some conjugate vaccines when necessary, like Hib and Prevnar. This is especially important because their immature immune system puts them at extra risk for Hib and pneumococcal disease. Why? These are “bacteria that are coated with polysaccharides.”
  • older infants and toddlers respond to other vaccines, including MMR and the chicken pox vaccine, once maternal antibodies began to fade and can no longer cause interference.

So vaccines work in babies and young infants, just like they do for older children, teens, and adults.

But that makes you wonder, if anti-vaccine folks don’t think that vaccines work in these younger children and that their immune system is so immature, then how can these vaccines overstimulate their immune system???

They don’t.

Both the immunogencity and safety of vaccines for infants are well studied.

What to Know About Your Baby’s Immature Immune System

Vaccines work well to help protect newborns and infants as their immune system continues to develop and mature.

More About Your Baby’s Immature Immune System

Do Pertussis Vaccines Work Against Pertactin-Negative Pertussis Bacteria?

Whooping cough is back!
This is not the first time that whooping cough has come back. We also saw a rise when folks got scared to use the DTP vaccine in the 1970s and 80s.

Pertussis vaccines aren’t perfect.

Few people claim that.

But what’s the problem with them?

Most experts think that the main issue is waning immunity.

While the acellular pertussis vaccines (DTaP and Tdap) that replaced the more effective whole cell pertussis vaccine (DTP) do work, the immunity they provide does not last as long as we would like.

They still work better than not getting vaccinated at all though.

Pertactin-Negative Pertussis Bacteria

What about the fact that we are starting to find pertactin-negative pertussis bacteria?

Does that mean that Bordetella pertussis, the bacteria that cause pertussis or whooping cough, have mutated and are causing a pertussis resurgence because they are resistant to the vaccine?

“CDC is currently conducting studies in the United States to determine whether pertactin deficiency is one of the factors contributing to the increase in the number of reported pertussis cases. CDC will continue to closely monitor the situation and evaluate all available scientific evidence before drawing any conclusions. There is also no suggestion that these new strains are causing more severe cases of pertussis.”

CDC on Pertactin-Negative Pertussis Strains

While an interesting theory that the anti-vaccine movement has latched on to, the answer seems to be no.

While pertactin-negative pertussis are certainly a thing, there is already evidence saying that they are not driving pertussis outbreaks – evidence that anti-vaccine folks like to ignore:

  • pertactin is only one of the components (antigens) of the pertussis bacteria that are in pertussis vaccines that help them to induce immunity. Others can include filamentous hemagglutinin, chemically or genetically detoxified pertussis toxin, and fimbrial-2 and fimbrial-3 antigens.
  • pertussis vaccines continue to be effective against pertactin-negative Bordetella pertussis bacteria
  • pertactin-negative Bordetella pertussis bacteria have not been found in all areas experiencing outbreaks of pertussis, as you would expect if they were driving these outbreaks
  • the first pertactin-negative Bordetella pertussis bacteria were found as early as the 1990s, long before we started using the current acellular versions of pertussis vaccines and before we started seeing an increase in outbreaks.

Also of note, pertactin-negative Bordetella pertussis bacteria do not cause more severe symptoms than pertactin-positive bacteria.

“Although pertussis vaccines aren’t perfect, vaccination remains our best prevention tool and we should continue to maintain high levels of DTaP coverage among children, sustain Tdap coverage in adolescents and increase Tdap coverage in adults and pregnant women. ”

CDC on Coughing up the Facts on Pertussis

Most importantly, it should be clear that pertussis vaccines work as we are not seeing pre-vaccine era levels of pertussis, even as we do see some outbreaks.

What To Know About Pertactin-Negative Pertussis

Pertactin-negative pertussis bacteria are not driving outbreaks of pertussis or whooping cough, and they have not become resistant to pertussis vaccines.

More About Pertactin-Negative Pertussis Bacteria

Antigen Counts in Vaccines

Vaccines contain antigens from toxins, viruses, or bacteria that help your body produce antibodies to help prevent future infections.

Of course, we are all exposed to these types of antigens every day.

In fact, experts state that we are exposed to thousands, if not millions, of antigens each day.

Eating. Drinking. Breathing. Touching things. These every day actions all can introduce antigens from viruses, bacteria, parasites, and toxins, etc., into our bodies.

And even though kids get many more vaccines today, and are protected against many more vaccine-preventable diseases than they once were, they actually get far fewer antigens from those vaccines than they once did.

Newer vaccines have a fraction of the antigens that the older DPT and smallpox vaccines once did.

That’s why the popular “too many too soon” anti-vaccine myth shouldn’t scare you from getting your kids vaccinated and protected.

Vaccine Antigen Counts

If you are still stuck on the actual number of vaccines, it is important to “understand that the numbers of antigens given are actually much less than they used to be. This is because we are giving purer vaccines. Vaccines have been isolated down to just the proteins needed to produce protection.”

The antigens are the things in the vaccines that actually trigger the production of antibodies and include antibody-stimulating proteins and polysaccharides.

In 1960, kids got up to 3,217 different antigens from the smallpox, polio, diphtheria, tetanus and whole cell pertussis vaccine.

In 1980, even as MMR replaced the smallpox vaccine, the antigen count in the vaccines kids got was still up to 3,041.

Kids Today Get Purer Vaccines

Even with many more vaccines, the number of different antigens that children will get with today’s immunization schedule is much lower than just 35 or 55 years ago:

  • DTaP/Tdap – 7 antigens
  • MMR – 24 antigens
  • IPV – 15 antigens
  • Hib – 2 antigens
  • Varicella – 69 antigens
  • Prevnar13 – 14 antigens
  • hepatitis A – 4 antigens
  • hepatitis B – 1 antigens
  • MCV4 – 5 antigens
  • HPV9 – 9 antigens
  • rotavirus – 15 antigens
  • Flu – 12 antigens

That’s just 177 different antigens in 12 vaccines that protect children against 16 vaccine-preventable diseases.

That’s still less than the 200 antigens that were in the smallpox vaccine that kids got 100 years ago.

Even considering that kids get multiple doses of many of these vaccines, with today’s complete vaccine schedule, from birth to age 18, including yearly flu shots, they would get a combined total of just 653 antigens. That’s still much less than a single dose of the DTP vaccine that kids got until 1997, when it was replaced by the DTaP vaccine.

With the 1980 immunization schedule, kids got 5 doses of DTP, 4 doses of OPV, a dose of MMR, and a dose of Td, combining to a grand total of at least 15,096 antigens.

Immune System Response to These Antigens

Of course, this is not to say that kids were exposed to too many antigens in vaccines in the past.

“Current studies do not support the hypothesis that multiple vaccines overwhelm, weaken, or “use up” the immune system. On the contrary, young infants have an enormous capacity to respond to multiple vaccines, as well as to the many other challenges present in the environment. ”

Offit et al on Addressing Parents’ Concerns: Do Multiple Vaccines Overwhelm or Weaken the Infant’s Immune System?

Looking at the antigen load of vaccines is simply another way to understand that kids don’t get too many vaccines too soon.

In fact, they get exposed to many more antigens from natural infections. A strep throat infection, for example, exposes kids to at least 25 to 50 antigens. That’s comparable to the antigens in the vaccines that infants get at their two month visit – the DTaP, IPV, HepB, Hib, and rotavirus vaccines combine to just 54 antigens.

But it is not just infections that lead to antigen exposures. Kids are exposed to 2,000 to 6,000 antigens every day and the “vaccines that children receive in the first two years of life are just a drop in the ocean when compared to the tens of thousands of environmental challenges that babies successfully manage every day.”

What to Know About Antigen Counts in Vaccines

Although kids get more vaccines today that their parents and grandparents, they get far fewer antigens from those vaccines.

More About Antigen Counts in Vaccines

Vaccine Ingredients

From antigens and adjuvants to preservatives, learn about common ingredients in vaccines and why they are safe.

What’s in Vaccines?

It is no secret what’s in our vaccines.

A list of ingredients is included on the vaccine’s package insert and can be found on a number of articles on the Internet.

In addition to other ingredients, a vaccine's package insert includes the viral or bacterial antigens that are in the vaccine.
In addition to other ingredients, a vaccine’s package insert includes the viral or bacterial antigens that are in the vaccine.

In addition to the active ingredients, the viral or bacterial antigens in the vaccine that you generate antibodies against, vaccines are made with a number of excipients, inactive substances or manufacturing by-products that are used to produce the vaccine:

  • preservatives – prevent bacterial and fungal contamination in multi-dose vials – thimerosal, 2-phenoxyethanol, phenol
  • adjuvants – help stimulate a stronger immune response so fewer antigens can be used – aluminum salts
  • stabilizers – maintain the potency of the vaccine and include sugars, amino acids, and proteins – lactose, MSG, gelatin
  • cell culture materials – what the vaccine antigens grow in – chicken egg proteins, yeast proteins, fetal bovine serum proteins
  • inactivating materials – kills viruses, inactivates toxins – formaldehyde
  • antibiotics – prevents bacterial contamination of the vaccine – neomycin, polymyxin B
  • suspending fluid – saline, etc.

Many of these excipients are removed from the final vaccine product and might only remain in residual amounts.

What’s Not in Vaccines?

Despite what myths you might have heard or read, many things are not in vaccines:

  • a vaginal spermacide
  • antifreeze
  • thimerosal – almost all vaccines, including over 130,000,000 flu vaccines this year, are thimerosal free!
  • aborted fetal tissue – there is no aborted fetal tissue or fetal parts in any vaccine, although some vaccines are made with fetal embryo fibroblast cells from cell lines that are derived (they can replicate infinitely) from two electively terminated pregnancies in the 1960s
  • Adjuvant 65 – an adjuvant that contained peanut oil that was tested with flu vaccines in the 1960s and continues to be blamed for causing peanut allergies, even though it has never been used in a vaccine

Vaccines are safe. Vaccine ingredients are safe.

What to Know About Vaccine Ingredients

Vaccines contain a number of ingredients that help them work stimulate a good immune response against particular viral and bacterial antigens to protect us against vaccine-preventable diseases.

More on Vaccine Ingredients