Tag: development

Et Tu, Slate? Flaws with Their Questions About Gardasil

Questioning vaccines doesn’t make someone anti-vaccine.

Something is missing in this article about Gardasil testing in Slate...
Something is missing in this article about Gardasil testing in Slate…

Doing a poor job of it and making folks scared to get vaccinated and protected?

I’ll let you decide what to call them…

Slate Investigates the Gardasil Clinical Trials

So after an eight-month long investigation, a journalist for Slate thinks he has evidence that the clinical trials that helped get Gardasil approved by the European Medical Agency were flawed.

What was the problem?

The way that they recorded possible side effects after folks were vaccinated.

“To track the safety of its product, the drugmaker used a convoluted method that made objective evaluation and reporting of potential side effects impossible during all but a few weeks of its years long trials.”

What made the method convoluted?

“In an internal 2014 EMA report about Gardasil 9 obtained through a freedom-of-information request, senior experts called the company’s approach “unconventional and suboptimal” and said it left some “uncertainty” about the safety results.

Merck, which is known as Merck Sharp & Dohme outside the U.S. and Canada, did not address the EMA’s safety concerns.”

When you read the internal 2014 EMA report about Gardasil 9, it is clear that Merck has a thorough response to each and every question that the EMA asked.

And those other quotes?

The EMA does state that:

  • “At all other time points in the study medical events were reported as “new medical history”. This is an unconventional and suboptimal study procedure.”
  • “While it is considered that the required safety data eventually has been made available for assessment, this feature of the study protocol brings some degree of uncertainty into safety assessment.”

So the EMA got the required safety data they were looking for, which is likely why Gardasil was approved in Europe.

They also said that “As the AE reporting procedure as seen at the inspection sites was in line with the approved protocol, the inspectors did not comment on it in the inspection reports. It was discussed with assessors during the course of the inspections, as in the inspectors’ opinion it is not an optimal method of collecting safety data, especially not systemic side effects that could appear long after the vaccinations were given.”

This case of a subject with POTS was reported as being "well characterized" by the EMA, even though it likely wasn't caused by her Gardasil shots.
This case of a subject with POTS was reported as being “well characterized” by the EMA, even though it likely wasn’t caused by her Gardasil shots.

But if it was suboptimal, how come they were able to record someone getting diagnosed with POTS 1,389 days after their third dose of vaccine?

I’m starting to understand why Dr. Yehuda Shoenfeld wasn’t quoted in the piece. He likely knew how it was going to be perceived…

“Imagining a link between HPV vaccination and CFS is not all that far-fetched, according to Dr. Jose Montoya, a professor of medicine at Stanford University and a CFS expert.”

Not far-fetched at all, which is why studies are done to see if there really is a link.

So even if part of the study design was suboptimal, the Slate piece shouldn’t have cherry picked those quotes and should have included these other big pieces of information:

  • A study in the UK using the MHRA’s Yellow Card passive surveillance scheme found no increase in reports of chronic fatigue syndromes following the introduction of Cervarix (another HPV vaccine)
  • In 2015, the EMA confirmed evidence that HPV vaccines do not cause complex regional pain syndrome (CRPS) and postural orthostatic tachycardia syndrome (POTS)
  • A large, nationwide register-based study from Norway found no indication of increased risk of chronic fatigue syndrome/myalgic encephalomyelitis following HPV vaccination
  • A large cohort study of over 2 million young girls in France found no risk for autoimmune diseases (including neurological, rheumatological, hematological, endocrine, and gastro-intestinal disorders)
  • A large cohort study of girls in Sweden with pre-existing autoimmune diseases found that HPV vaccination was not associated with increased incidence of new-onset autoimmune disease (49 types of autoimmune diseases)
  • A review of VAERS reports that “did not detect any unusual or unexpected reporting patterns that would suggest a safety problem” with HPV vaccination

The Slate piece does mention two of these studies, but just barely. One gets a single sentence and the other, half a sentence.

We see page after page of anecdotes of folks with supposed vaccine injuries, but the evidence that shows the vaccine is safe is almost buried and easy to miss. Many of the other studies seem to be left out.

And just because these patients have agonistic auto-antibodies, it doesn’t mean that they are from a vaccine.

“Five of the 14 POTS subjects and 2 of the 10 “healthy controls” recalled a respiratory infection in the 6 months prior to onset of their symptoms or inclusion in the study for the healthy controls.”

Li et al on Autoimmune Basis for Postural Tachycardia Syndrome

Lastly, what’s with calling cervical cancer uncommon???

“Cervical cancer is the 4th most common cause of cancer death in women worldwide, with tens of thousands of deaths in Europe each year despite the existence of screening programmes to identify the cancer early.”

European Medicines Agency

Downplaying the risks of vaccine-preventable diseases, while trying to scare folks about vaccines – that’s what gets you labeled as anti-vaccine.

The HPV vaccines are safe. They work and they are necessary. Don’t skip them.

What to Know About the Slate Gardasil Investigation

Although the study design for Gardasil used for licensing in Europe might have been suboptimal, that doesn’t really come across in this Slate piece, as it seems clear that it didn’t result in safety data being missed, and as post-licensure tests have confirmed, Gardasil is safe.

More on the Slate Gardasil Investigation

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

Vaccines Are Made in China!

It shouldn’t be a secret that vaccines are made in China.

There are over 1.3 billion people in China, and no, they don’t import all of their vaccines from the United States.

Neither does India, for all of their 1.2 billion people.

For example, the Serum Institute of India Pvt. Ltd. makes many vaccines, including:

  • GeneVac-B – hepatitis B
  • Quadrovax – DTP-Hib combo
  • Pentavac – DTP-HepB-Hib combo
  • Tresivac – MMR
  • Poliovac – polio
  • Triple Antigen – DTP
  • MenAfriVac – meningococcal group A
At least 34 manufacturers make vaccines for use in China, like this Hib vaccine.
At least 34 manufacturers make vaccines for use in China, like this Hib vaccine.

And there are over 34 vaccine manufacturers in China, including:

  • Chengdu Institute of Biological Products Co., Ltd
  • Hualan Biolgical Bacterin Co., Ltd
  • Jilin Brother Biotech Co., Ltd
  • Wuhan Institute of Biological Products
  • Lanzhouz Institute of Biological Products

These vaccine manufacturers in China, a mix of state run, private, and international joint ventures, help produce the vaccines used in China’s immunization program.

Some US vaccine companies even have vaccine manufacturing plants in China and other countries, but they make vaccines that are used in nearby parts of the world.

For example, Merck recently opened a new vaccine plant in Hangzhou, China to make vaccines to be used in the Asia Pacific region.

Should We Be Concerned About Vaccines Made in China?

If you are getting vaccinated in China, then you likely want to know more about where and how your vaccines are made. Everyone else should probably be wondering why anti-vaccine folks make such a fuss about this.

In addition to implying that vaccines are made under unsafe conditions, much of this anti-vaccine propaganda includes racist themes.

Parents who are concerned should understand that the United States doesn’t get any vaccines from China or India, or from Brazil, Cuba, Indonesia, or Russia for that matter.

The concern, of course, would be that it might be hard to test and verify these vaccines if they were.

“Following approval, FDA also carefully monitors the quality of vaccines—all manufactured lots must pass tests before they can be used. And as with all manufacturers of medical products, vaccine manufacturers must follow strict manufacturing standards. In addition, FDA conducts routine inspections of manufacturing sites.”

FDA on How does FDA assess the safety of vaccines?

Instead, vaccines that are used in the United States are made by:

  • Emergent Biosolutions – USA – Anthrax vaccine
  • ID Biomedical Corp – Canada – Fluvaval
  • GSK Vaccines – based in Belgium, but vaccines are made in Belgium (Boostrix, Cervarix, Energix-B, Havrix, Hiberix, Infanrix, MenHibrix, Kinrix, Pediarix, Rotarix), Germany (Boostrix, Fluarix, Infanrix, Kinrix, Pediarix, Rabavert), and Italy (Bexsero, Menveo)
  • MedImmune – USA – FluMist
  • Merck – USA – BCG, Gardasil9, MMRII, PedvaxHIB, PneumoVax23, ProQuad, RecombivaxHB, RotaTeq, Vaqta, Varivax, Zostavax are made at Merck’s vaccine manufacturing plants in West Point, Pennsylvania, Elkton, Virginia, and Durham, North Carolina
  • PaxVax – USA – their Vivotif typhoid vaccine is made in Thörishaus, Switzerland
  • Pfizer – USA – (Prevnar, Trumenba)
  • Protein Sciences Corporation – USA – Flublok
  • Sanofi Pasteur – Canada (Adacel, Daptacel, Pentacel), France (IPOL, Pentacel), USA (Menactra, YF-Vax, ),
  • Seqirus – USA – Afluria, Flucelvax, Fluvirin
  • Valneva (Intercell USA) -their  Japanese encephalitis vaccine (IXIARO) is made in Livingston, Scotland, UK
  • Valneva Sweden AB – their Dukoral cholera vaccine is made in Solna, Sweden

A little competition in the vaccine industry wouldn’t be a horrible thing though.

Vaccines are expensive

They are safe, but expensive. Necessary too.

What to Know About Vaccines Made in China

Although plenty of vaccines are made in China, the vaccines that are used in the United States are not, although anti-vaccine folks use this as a talking point to scare parents away from vaccinating and protecting their kids.

For More Information on Vaccine Manufacturer Sites:

Are Vaccines Evaluated for Mutagenicity, Carcinogenicity or Impairment of Fertility?

Spend much time on anti-vaccine websites or forums and you will soon be warned that vaccines are not evaluated for mutagenicity, carcinogenicity or impairment of fertility.

Actually, you can often read that simply by reading a vaccine’s package insert.

Mutagenicity, Carcinogenicity and Impairment of Fertility

What are these term exactly?

  • mutagenicity – being known or suspected of causing mutations in our DNA, which can lead to cancer
  • carcinogenicity – being known or suspected of being able to cause cancer
  • impairment of fertility

And why are they listed in Section 13 of a vaccine’s package insert?

The Section 13 Vaccine Conspiracy?

More importantly, why do some folks talk about Section 13.1 of a vaccine’s package insert like it is Area 51 or Agenda 21?


13.1 Carcinogenesis, mutagenesis, impairment of fertility. This subsection must state whether long term studies in animals have been performed to evaluate carcinogenic potential and, if so, the species and results. If results from reproduction studies or other data in animals raise concern about mutagenesis or impairment of fertility in either males or females, this must be described. Any precautionary statement on these topics must include practical, relevant advice to the prescriber on the significance of these animal findings. Human data suggesting that the drug may be carcinogenic or mutagenic, or suggesting that it impairs fertility, as described in the “Warnings and Precautions” section, must not be included in this subsection of the labeling.”

CFR – Code of Federal Regulations Title 21

So no material for a vaccine conspiracy?

Just information on studies in animals?

“The goals of the nonclinical safety evaluation generally include a characterization of toxic effects with respect to target organs, dose dependence, relationship to exposure, and, when appropriate, potential reversibility. This information is used to estimate an initial safe starting dose and dose range for the human trials and to identify parameters for clinical monitoring for potential adverse effects. The nonclinical safety studies, although usually limited at the beginning of clinical development, should be adequate to characterize potential adverse effects that might occur under the conditions of the clinical trial to be supported.”

FDA on Guidance for Industry M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals 

It still sounds important though…

Are Vaccines Evaluated for Mutagenicity, Carcinogenicity or Impairment of Fertility?

As important as vaccines are, no one wants them to mutate our children, cause cancer, or keep them from having babies.

Fortunately, they don’t!

“To ensure the safety of new vaccines, preclinical toxicology studies are conducted prior to the initiation of, and concurrently with, clinical studies. There are five different types of preclinical toxicology study in the evaluation of vaccine safety: single and/or repeat dose, reproductive and developmental, mutagenicity, carcinogenicity, and safety pharmacology. If any adverse effects are observed in the course of these studies, they should be fully evaluated and a final safety decision made accordingly. ”

M.D. Green on the Preclinical Toxicology of Vaccines

And that’s because vaccines are safe and well tested.

Then why do anti-vaccine folks scare parents into thinking that vaccines are missing necessary testing when the package insert states that they are “not evaluated for mutagenicity, carcinogenicity or impairment of fertility?”

Cancer is caused by a host of factors. Vaccines have a role in preventing and potentially treating some types of cancer. Components of vaccines and their associated cell lines that viruses are grown in are safe and have not been shown to induce cancer in the vaccinated host.
“Cancer is caused by a host of factors. Vaccines have a role in preventing and potentially treating some types of cancer. Components of vaccines and their associated cell lines that viruses are grown in are safe and have not been shown to induce cancer in the vaccinated host.”

Probably because it sounds scarier than saying that vaccines have a low risk of inducing tumors and that there are very specific guidelines and rules for when a manufacturer needs to perform fertility studies.

That means that if  a package insert says that it has “not been evaluated,” it is simply because it was not necessary or appropriate. It is not because they just didn’t want to do it and left those tests out.

That doesn’t sound as scary though.

All necessary pre-clinical or nonclinical testing is done on vaccines and their components. You just don’t see long term testing that would be listed in the package insert unless the initial tests found a problem.

Also remember that vaccines are monitored through several passive and active safety systems that would detect issues with mutagenicity, carcinogenicity, and impairment of fertility.

And several vaccines actually prevent cancer!

What to Know About Vaccines and Mutagenicity, Carcinogenicity and Impairment of Fertility

Vaccines are appropriately evaluated for mutagenicity, carcinogenicity and impairment of fertility, when necessary, as a part of pre-clinical or nonclinical studies that occur even before the first phase one studies on people.

More About Vaccines and Mutagenicity, Carcinogenicity and Impairment of Fertility


Vaccine Testing and Development Timeline and Myths

New vaccines must go through a long journey before they are finally approved by the FDA and get added to the recommended immunization schedule.


Vaccine Testing and Development Myths

There are many myths and much misinformation surrounding vaccine testing and development that is used to scare parents away from vaccinating their kids.

Have you heard that vaccines aren’t tested together?

Or that flu vaccines or Tdap were never tested on pregnant women?

Then there are the myths about fast-tracking, and that important steps are skipped when a vaccine is on fast track for FDA approval, or that the whole vaccine testing and development process happens very quickly.

Vaccine Testing and Development Timeline

The vaccine development process is anything but quick.

“Vaccine development is a long, complex process, often lasting 10-15 years and involving a combination of public and private involvement.”

The History of Vaccines on Vaccine Development, Testing, and Regulation

During this time of the exploratory and pre-clinical stage research and then phase 1,2, and 3 trails, vaccines are:

  • tested on animals
  • tested on small groups of people
  • tested on larger groups of people
  • tested alone
  • tested together with other vaccines
  • tested for safety
  • tested for efficacy (to make sure they work)

This often includes double-blind, placebo controlled vaccine trials.

Fast tracking does speed the process up, but not because any of the testing is skipped. The researchers just get more frequent meetings and communication with the FDA and “Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met.”

“Vaccine development is a complex multidisciplinary activity, combining understanding of host-pathogen interactions at the molecular level, with clinical science, population-level epidemiology and the biomechanical requirements of production.”

Anthony L. Cunningham, et al on Vaccine development: From concept to early clinical testing

Testing doesn’t stop once a vaccine is approved by the FDA and is added to the immunization schedule either. We often continue to see testing for vaccine safety and efficacy using phase 4 trials and with our post-licensure vaccine safety system, including VAERS and the Vaccine Safety Datalink.

And of course testing continues long after we begin using vaccines to see how long their protection will last. For example, because of continued testing, we now know that Gardasil and Cervarix are providing protection that lasts at least 8 and 9 years.

What To Know About Vaccine Testing and Development

From pre-clinical studies and years of phase 1, 2, and 3 trials to continued monitoring after a vaccine is approved and added to the immunization schedule, the vaccine testing and development process helps make sure that vaccines are safe and that they work.

More About Vaccine Testing and Development

Vaccine Timeline and History of Vaccines

Most people are aware of the big historic dates and events related to vaccines.

For example, they might now when Edward Jenner first tested his smallpox vaccine (1798), when the first polio vaccine was licensed by Jonas Salk (1955), or that we just got a Meningococcal B vaccine (2014).

Smallpox was officially declared to have been eradicated in December 1979.
Smallpox was officially declared to have been eradicated worldwide in December 1979.

But few likely now that we have had rabies vaccines since 1885, a flu vaccine since 1945, or that the last case of wild polio in the United States was in 1979.

“It is hard to fully appreciate how vaccines have revolutionized modern medicine. The long schedule of vaccines may seem like a hassle, and rumors about harmful effects unnerve parents. But, the fact is, vaccines have helped save millions and millions of lives. Just a few generations ago, people lived under the constant threat of deadly infectious diseases, like smallpox, polio, and hepatitis.

Let’s look at the greatest infectious scourges of the past 1,000 years and how vaccines have mitigated or even eradicated the danger.”

Public Health Understanding Vaccines

From historical safety concerns, like the Cutter Incident in 1955 or the withdrawal of the first rotavirus vaccine in 1999, to improvements in vaccine safety and the control, elimination, and eradication of vaccine-preventable diseases, understanding the history of vaccines can help you get educated and understand that vaccines work and that they are safe and necessary.

Early History of Vaccination

In the early history of vaccination we had the the smallpox vaccine and the beginning of the pre-vaccine era – the first vaccines.

  • Lady Mary Wortley Montagu brings variolation to England to prevent smallpox
  • George Washington mandated that every soldier in the Continental Army had to be inoculated against smallpox
  • Edward Jenner conducts experiments in 1796 that led to the creation of the first smallpox vaccine a few years later and replaces variolation as a preventative for smallpox
  • *Dr. Luigi Sacco becomes the Jenner of Italy
  • James Madison, one of the Founding Fathers, signed the Vaccine Act of 1813 – An Act to encourage Vaccination.
  • a vaccine for rabies is developed by Louis Pasteur in 1885
  • vaccines for cholera and typhoid were developed in 1896 and a plague vaccine in 1887
  • the first diphtheria vaccine is developed in about 1913 through the work of Emil Adolf Behring, William Hallock Park, and others
  • the first whole-cell pertussis vaccines is developed in 1914, although it will take several decades before they are more widely used
  • a tetanus vaccine is developed in 1927
  • 12 children die when a multi-use bottle of diphtheria vaccine that didn’t contain a preservative became contaminated with bacteria in the Queensland Disaster in 1928
  • Max Theiler develops the first yellow fever vaccine in 1936
  • the AAP formally approves the use of a pertussis vaccine created by Pearl Kendrick and Grace Eldering in 1943
  • the first flu vaccine is licensed for use in the US in 1945

End of the Pre-Vaccine Era

In the mid-20th century, we started to get vaccines to control diseases that many of us have never seen, like polio, measles, and rubella.

  • the individual diphtheria, tetanus, and pertussis vaccines become combined in a single DTP vaccine in 1948
  • the last smallpox outbreak in the United States kills one person, Lillian Barber, in the Rio Grande Valley of South Texas in 1949
  • the Salk inactivated polio vaccine (IPV) is introduced in 1955
  • President Dwight D Eisenhower signed the Polio Vaccination Assistance Act in 1955, which gave $30 million in federal grants to states to cover the costs of planning and conducting polio vaccination programs, including purchasing polio vaccine
  • about 200 children develop polio in 1955 from contaminated polio vaccines in what becomes known as the Cutter Incident
  • the live, oral Sabin polio vaccine (OPV) replaces the Salk polio vaccine in 1962
  • President John F Kennedy signed the Vaccination Assistance Act in 1962 (Section 317 of the Public Health Service Act), which started as a three year program to help get kids vaccinated against polio, diphtheria, tetanus, and pertussis, but it has been continuously reauthorized ever since
  • the first live measles vaccine was licensed in 1963 but was replaced with a further attenuated measles virus that caused fewer side effects in 1968
  • President Lyndon B Johnson established a legacy of US leadership in global immunization by funding the CDC Smallpox Eradication program in 1965
  • the MMR vaccine becomes available in 1971, combined the vaccines for measles, mumps (licensed in 1967), and rubella (1969), and was routinely given when toddlers were about 15 months old
  • routine vaccination with smallpox vaccines end in the US in 1972

The Vaccination Era

The end of the 20th century brought more vaccines and protection against even more now vaccine preventable diseases.

  • Pneumovax, the first pneumococcal vaccine that protects kids and adults from certain types of Streptococcus pneumoniae bacteria is approved in 1971 and is given to high-risk kids
  • President Jimmy Carter’s  National Childhood Immunization Initiative in 1977 reached its goal of immunizing 90% of children
  • the Thirty-Third World Health Assembly declares that smallpox is eradicated in 1979
  • Menomune, the first meningococcal vaccine is licensed in 1981 and is recommended for high-risk kids until it is later replaced by Menactra
  • a plasma-derived hepatitis B vaccine is licensed in 1981
  • Vaccine Roulette, a controversial news segment, airs in 1982 and attempts to associate the DPT vaccine with permanent brain damage, downplays the risks of pertussis disease and helps start much of the modern American anti-vaccine movement
  • a Haemophilus b capsular polysaccharide vaccine is licensed in 1985, but unfortunately does not provide good protection in kids younger than 18 to 24 months, who are most at risk for Haemophilus influenzae Type b disease
  • a recombinant hepatitis B vaccine (Recombivax HB) is approved in 1986 but is only recommended to be used in those at high risk for infection
  • another hepatitis B vaccine, Engerix-B, is approved in 1989
  • the first Haemophilus b conjugate vaccine (PRP-D) is approved in 1988 to provide protection against Haemophilus influenzae type b disease in all kids at least 18 months old, but in 1990, they are replaced with two improved Hib conjugate vaccines (PRP-HbOC and PRP-OMP) that can be given to infants as young as two months old
  • a booster dose of MMR is first recommended in 1989, but only for kids who live in counties that have at least 5 cases of measles. The routine 2 dose MMR schedule wasn’t put into use for all kids until 1994.
  • the Vaccine Adverse Events Reporting System (VAERS) is established in 1990
  • the hepatitis B and Hib vaccines are recommended for all infants in 1991
  • after year’s of neglect under President Reagan, President George HW Bush’s immunization action plan in 1991 once again raised immunization rates following three years of measles outbreaks
  • the DTaP vaccine, which is supposed to have fewer side effects than DTP is licensed, and by 1997 replaces DTP for all required doses, although DTP is never actually shown to have caused seizures or brain damage, as was once claimed in Vaccine Roulette
  • President Bill Clinton’s Childhood Immunization Initiative in 1993 includes signing the Vaccines for Children (VFC) Act, providing free vaccines to many children
  • the WHO declares that polio has been eliminated from the Western Hemisphere in 1994
  • a vaccine to protect kids against chicken pox (Varivax) is licensed in 1995
  • VAQTA, the first hepatitis A vaccine is approved by the FDA in 1996 for kids who are at least two years old, but is mainly given to kids at high risk to get hepatitis A
  • the Salk inactivated polio vaccine (IPV) is once again recommended for kids and replaces the oral polio vaccine (OPV) in 1996 because of a small risk of vaccine-associated paralytic poliomyelitis (VAPP), beginning with a sequential IPV-OPV vaccine schedule and then going to an all IPV schedule in 2000
  • RotaShield, the first rotavirus vaccine is licensed in 1998 but is soon withdrawn from the market in 1999 after it is associated with an increased risk of intussusception, a form of bowel obstruction
  • LYMErix, a Lyme disease vaccine, is licensed in 1998
  • Dr. Andrew Wakefield publishes a report in the journal Lancet and attempts to link the MMR vaccine to autism
  • thimerosal is removed from the vast majority of vaccines in the childhood immunization schedule in 1999 and 2000
  • endemic measles is declared eliminated in the United States in 2000
  • Prevnar, a newer pneumococcal vaccine is licensed in 2000 and is added to the immunization schedule the next year
  • LYMErix goes off the market because of insufficient sales in 2002
  • Flumist, a live, intranasal flu vaccine, is approved in 2004
  • endemic rubella is declared eliminated in the United States in 2004
  • a flu shot for all healthy children between 6 and 23 months became a formal recommendation for the 2004-05 flu season.
  • beginning in the 2004-05 flu season, a flu shot is recommended for women who will be pregnant during flu season, in any trimester, which is different than previous recommendations for a flu vaccine if a women was going to be beyond the first trimester of pregnancy during flu season. Unfortunately, even though they are in a high-risk category, only about only 13% of pregnant women received a flu vaccine in 2003.
  • Havrix, another hepatitis A vaccine, is approved in 2005 and the age indication for both hepatitis A vaccines is lowered to 12 months.
  • Menactra, a vaccine to protect against certain types of meningococcal disease is licensed in 2005 and is added to the immunization schedule in 2006, being recommended for all at 11 to 12 years of age or when they enter high school
  • the Tdap vaccine (Boostrix or Adacel) is recommended for teens and adults to protect them from pertussis in 2006 and replaces the previous Td vaccine that only worked against tetanus and diphtheria
  • RotaTeq, another rotavirus vaccine, is licensed in 2006, and is added to the immunization schedule in 2007
  • the hepatitis A vaccine is added to the routine childhood immunization schedule in 2006
  • Gardasil, the first HPV vaccine, is approved in 2006
  • a shingles vaccine, Zostavax, is approved for adults in 2006
  • a 2nd booster dose of the chicken pox vaccine is added to the immunization schedule in 2007 to help prevent breakthrough infections

The Post Vaccination Era

Why call it the post-vaccination era?

It has been some time since a vaccine for a new disease has been added to the routine vaccination schedule, but we are also starting to see more and more outbreaks of old diseases, especially pertussis, mumps, and measles.

  • another rotavirus vaccine, RotaRix, is approved in 2008
  • another HPV vaccine, Cervarix, is approved in 2009
  • another meningococcal vaccine, Menveo, is approved in 2010
  • a newer version of Prevnar, which can provide coverage against 13 strains of the pneumococcal bacteria, is approved and replaces the older version (Prevnar 7) in 2010
  • Fluzone Intradermal and Fluzone High-Dose are two new flu vaccine options that became available in 2011
  • a combination vaccine that protects against both Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y was approved by the FDA in 2013. MenHibrix is recommended for infants at high risk for meningococcal disease.
  • Quadrivalent flu vaccines, which protect against four strains of flu, become available for the 2013-14 flu season
  • Trumenba, the first vaccine to protect against serogroup B Meningococcal disease is approved by the FDA (October 2014). Previously, Bexsero, a MenB vaccine that is approved in some other countries, was given to some college students during outbreaks under the FDA’s expanded access program for investigational products. Both are now recommended by the ACIP for those at increased risk for meningococcal serogroup B infections.
  • Gardasil 9 is approved by the FDA (December 2014) to provide protection against five additional types of HPV.
  • Cervarix is discontinued in the US in 2016 because of poor sales
  • Vaxchora is approved to in 2016 for adults traveling to cholera-affected areas
  • MenHibrix is discontinued in the US in 2016 because of low demand
  • Menomune is discontinued in the US in 2017 as it was long ago replaced by the new meningococcal vaccines Menactra and Menveo

More Information About Vaccine Timelines

Updated February 7, 2018


Discontinued Vaccines

The Tripedia DTaP vaccine was discontinued in 2013.

Most people know that the RotaShield rotavirus vaccine was discontinued in 1999 because it was found to be linked to intussusception.

It took eight years for a new rotavirus vaccine to be licensed.

Lymerix, a Lyme disease vaccine was discontinued in 2002. Unfortunately, we still don’t have a new replacement Lyme disease vaccine.

Vaccines That Have Been Discontinued

More commonly, a vaccine gets discontinued with little notice, as there are other options to keep kids vaccinated and protected.

Other vaccines that are no longer made, include:

  • Menomume – an older meningococcal polysaccharide vaccine was discontinued in 2017 in the US as it was replaced with the newer meningococcal conjugate vaccines Menactra and Menveo.
  • MenHibrix – a meningococcal – Hib combination vaccine that was discontinued in the US in 2016 due to low demand
  • Cervarix – an HPV vaccine that was discontinued in the US in 2016 due to low demand
  • Comvax –  a Hib/Hepatitis B combination – discontinued in 2014
  • Tetanus toxoid – discontinued 2013
  • Tripedia – a DTaP vaccine – discontinued 2011
  • TriHIBit – a DTaP/Hib combination
  • JE-VAX – discontinued 2005
  • Attenuvax – measles vaccine
  • Mumpsvax – mumps vaccine
  • Meruvax II – rubella vaccine
  • M-R-Vax – measles and rubella combo
  • M-M-Vax – measles and mumps combo
  • Biavax II – rubella and mumps combo
  • Heptavax-B – the original hepatitis B vaccine
  • HIB-Vax – the original Hib vaccine
  • Plague vaccine
  • Poliovax
  • Dryvax – smallpox vaccine
  • Measles-Smallpox combination vaccine
  • Diptussis – a diphtheria/pertussis combination (1949-55)
  • Quadrigen – a DTP/Polio combination (1959-68)
  • Streptococcus vaccine (1952-88)
  • Serobacterin – a pertussis vaccine (1945-54)
  • Rocky mountain spotted fever vaccine (1942-78)
  • Typhus vaccine (1941-79)
  • smallpox vaccine (1917-1976)

Most of these vaccines were discontinued because they simply became obsolete.

Orig. Title: SPvac806.8a
A smallpox vaccination kit included the diluent, a vial of Dryvax smallpox vaccine, and a bifurcated needle.

The Hib-Vax and Heptavax-B vaccines, for example, both use older technology, so these vaccines were discontinued when newer Hib and hepatitis B vaccines were introduced.

And some vaccines are discontinued  or are phased out when they get an update:

  • MMR -> MMR-II (1978)
  • Prevnar 7 -> Prevnar 13 (2010)
  • Gardasil -> Gardasil 9 (2014)

Still other vaccines, like Tripedia and TriHIBit, seemed to get discontinued as a business decision. Through mergers, Sanofi Pasteur, Ltd. ended up with two DTaP vaccines. They had their own Daptacel, but also had Tripedia, a vaccine they acquired from Pasteur Merieux. They ended up discontinuing Tripedia.

Merck also stopped making Comvax not because of “any  product safety or manufacturing issues,” but rather “as part of its ongoing effort to focus company resources on opportunities that provide the greatest value for customers, patients, and public health…”

Cervarix was discontinued because of low market demand. The competing HPV vaccine, Gardasil, had the much larger market share.

Vaccine Manufacturers and Discontinued Vaccines

And of course, some vaccine manufacturers simply stopped making vaccines.

The Texas Department of Health Resources once had a license to make vaccines, including DTP, diphtheria, DT, pertussis, tetanus, Td, and typhoid vaccines since 1950. They completely exited the vaccine market in 1979.

In the 1970s and 80s, dozens of vaccines were discontinued as Miles Inc., Eli Lilly, Parke Davis, and other companies stopped making vaccines.

While that is often downplayed these days, it is important to realize that we used to have much more competition among vaccine manufacturers. For example, in the early 1970s, the DTP vaccine was made by at least 11 different companies! We now have just two that make DTaP. And in many other cases, like for Prevnar, MMR-II, polio, and the chicken pox vaccine, there is just one manufacturer.

For More Information on Discontinued Vaccines:

Updated on February 7, 2018