Tag: antigens

What Is a Hexavalent Vaccine?

Most folks know that we have combination vaccines that help reduce the number of injections that kids have to get at one visit.

You might not think of it as a combination vaccine, but one of the first, DPT, simply combines protection against diphtheria, pertussis, and tetanus into one shot.

Of course, we have come a long way since the days when DPT and MMR were considered combination vaccines.

Wait, why aren’t they considered combination vaccines anymore?

It’s not part of any conspiracy. It’s simply because you can’t get their individual components separately anymore. There is no measles or rubella shots anymore. Just the MMR. There is no tetanus shot.

Combination Vaccines

Not surprisingly, it is now becoming routine for kids to get combination vaccines instead of separate shots.

That’s because while the great majority of us want our kids vaccinated and protected, few enjoy shots and needles.

“The use of licensed combination vaccines is preferred over separate injection of their equivalent component vaccines.”

AAP on Combination Vaccines for Childhood Immunization

Does this mean more vaccines at one visit?

Nope.

“So, at a doctor’s visit, your child may only get two or three shots to protect him from five diseases, instead of five individual shots. Fewer shots may mean less pain for your child and less stress for you.”

CDC on Combination Vaccines

It just means fewer injections.

Combination vaccines combine the vaccines that you are already getting into one injection.

What Is a Hexavalent Vaccine?

And they might get even fewer with the latest hexavalent vaccines (six-in-one).

This is the next step up from our current pentavelent vaccines (five-in-one), like Pediarix (combines DTaP, Hep B, and IPV) and Pentacel (combines DTaP, IPV, and Hib).

The hexavalent vaccines combine protection against diphtheria, tetanus, acellular pertussis, Haemophilus influenzae type B, poliovirus and hepatitis B (DTaP-Hib-IPV-HepB) into one injection.

Sounds good, right?

Although not approved in the United States, hexavalent vaccines, including Infanrix Hexa have been used in many other countries since 2000! Another, Hexavac was withdrawn from the market because of issues with waning hepatitis B antibody titers (kids had levels that were still protective, but were on the low side).

When will get a hexavalent vaccine in the United States?

Obviously, the early problems with Hexavac kept us from getting a hexavalent vaccine, at least before the next generation of vaccines was developed.

Hexavalent vaccines are widely available in most parents of the world.
Hexavalent vaccines are widely available in most parents of the world.

Two new hexavalent vaccines, Vaxelis and Hexyon, have recently been licensed in Europe, after many studies showed that they worked and were safe when given with all of the other vaccines on the schedule, including Prevnar, rotavirus, Men C, and MMRV.

And one of these might soon be coming to the United States.

V419 (Vaxelis), which was developed in collaboration between Merck and Sanofi Pasteur, has been under review by the FDA since 2014 has already received a Complete Response Letter that was “deemed complete and acceptable for review.”

Hopefully that means we will get a hexavalent vaccine soon.

Remember, that could mean just two shots at infant well check ups, but continued protection against eight vaccine-preventable diseases, as they get a hexavalent vaccine, Prevnar and the rotavirus vaccine!

More on the Hexavalent Vaccine

Why Do Some Vaccines Need Boosters?

Vaccines work.

They aren’t perfect though, which is why some vaccines need booster doses to help them provide long lasting protection.

Why Do Some Vaccines Need Boosters?

To be clear, just because you get more than one dose of a vaccine, that doesn’t make it a booster dose.

For example, infants get multiple doses of the DTaP, polio, Hib, hepatitis B, Prevnar, and rotavirus vaccines, but those are part of the primary series for those vaccines. They aren’t boosters.

“A “classical” prime-boost immunization schedule is, thus, to allow 4 to 6 months to elapse between priming and booster doses, hence the generic “0-1-6 month” (prime-prime-boost) schedule. Secondary antigen exposure thus results in the production of higher-affinity antibodies than primary responses.”

Plotkin’s Vaccines (Seventh Edition)

Getting the booster shot in a vaccine series is important to get full protection.
Getting the booster dose in a vaccine series is important to get full protection.

Classic booster doses are the:

But why do we need these booster doses?

While one or more doses of the primary series of the vaccine leads to the production of plasma cells and protective antibodies, the booster dose then causes a secondary immune response and the production of more long-lived plasma cells. That’s how we get higher levels of protective antibodies that will last longer.

Which Vaccines Don’t Need Boosters?

In general, live vaccines don’t need booster doses.

So why do we get a second dose of MMR?

This isn’t a classic booster dose. It protects the small percentage of people who don’t respond to the first dose.

Some folks may need a booster dose of the MMR vaccine in certain circumstances though, specifically if they are caught up in a mumps outbreak.

What to Know About Vaccine Booster Doses

Some vaccines need booster doses to help you get full protection. Don’t skip them.

More on Vaccine Booster Doses

Aren’t Vaccines Made for Adults?

Have you ever heard someone bring up the argument that vaccines are made for adults, so kids shouldn’t be getting the same dosage?

If they do, you should understand right away that they don’t really understand how vaccines work.

And that they really don’t understand immunology either, for that matter.

Are Vaccines Made for Adults?

To be fair, some vaccines are made just for adults. In fact, some, like the shingles vaccines and high-dose flu shot (has four times the amount of antigen in the regular flu shot) are only for seniors.

Other vaccines, like the rotavirus vaccine, are made just for kids.

And a few vaccines come in different forms depending on your age.

For example, younger kids get the DTaP vaccine, while older kids and adults get a Tdap vaccine. They both protect against the same three diseases (diphtheria, tetanus, and pertussis), but they contain different amounts of antigens. In this case, the Tdap vaccine actually contains 3-5 times less of the diphtheria component as the DTaP vaccine. That’s because before they lowered it, repeated dosing of the original Td vaccine every ten years led to worsening local reactions in some people.

The hepatitis B and hepatitis A vaccines are also available in different formulations for kids and adults, with adults getting twice the amount of antigens.

Most other vaccines though, come in the same form for both kids and adults, including the MMR vaccine and vaccines that protect us against HPV, chicken pox, polio, meningococcal disease, and pneumococcal disease, etc.

Are Vaccines Calibrated by Weight or Age?

Why does this question even come up?

Science event in Washington, D.C. reminding folks that Vaccines Work.
Pediatricians at the March for Science event in Washington, D.C. reminded folks that Vaccines Work. We shouldn’t forget that others also need a reminder of how they work.

It’s because some folks push the myth that infants are getting too high a dose of vaccines, since in most cases, older kids and adults get the very same dose.

They don’t though.

Does that mean that those older kids and adults are getting too low a dose then?

Nope.

You see, vaccines aren’t like antibiotics or other medications. They aren’t typically dosed based on your weight or age and don’t have to build up to a steady state in your blood stream.

That’s right, for most vaccines, it doesn’t matter if your child weighs 8 pounds or 80 pounds.

Why not?

Because the antigens in the vaccine don’t have to travel all around your child’s body in order for them to work!

Understanding the Immune Response to a Vaccine

Instead, the small amount of antigens in a vaccine simply get the vaccine response started near where the vaccine was given, whether that is in their arm or leg (shot), nose (nasal), or small intestine (oral).

“B cells are essentially activated in the lymph nodes draining the injection site.”

Claire-Anne Siegrist on Vaccine Immunology

Antigen-presenting cells (APCs) then take up the antigens and migrate towards a nearby lymph node. It is at these lymph nodes that the APCs activate other cells, including:

  • antigen-specific helper T cells
  • killer T cells
  • B cells

The activated T and B cells then go to work, with many B cells becoming plasma cells, and some T and B cells transforming into memory cells.

This illustration from the NIH and National Library of Medicine helps explain how vaccines work.
This illustration from the NIH and National Library of Medicine explains how vaccines work.

Next, within days to weeks of getting vaccinated, the plasma cells begin producing protective antibodies, which are released into our bloodstreams.

The same thing happens if you are exposed to a disease naturally, which is why it is silly to think that a vaccine could weaken or overwhelm your immune system.

The big difference about getting exposed to a disease naturally vs getting a vaccine? With the vaccine, you don’t have to actually have the the symptoms of the disease or any of its complications to get immunity. In other words, you don’t have to earn your immunity.

What to Know About Vaccine Dosage Myths

The dose of vaccines for kids and adults is not calibrated by weight or age because the immune reaction that helps antibodies travel all through your body starts locally, near where the vaccine was given.

More on Vaccine Dosage Myths

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.”

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