Tag: development

Making a Better Pertussis Vaccine

So we know that we need a better pertussis vaccine.

DTaP and Tdap just aren’t doing the job that they should be doing.

Whooping Cough is back, again.
Whooping Cough is back, again.

So when will we get one?

Making a Better Pertussis Vaccine

Since anti-vaccine folks are always talking about the 300 new vaccines in the pipeline, you would think that we would have had several new pertussis vaccines by now…

Unfortunately, we don’t.

What we do have is some good candidates, including:

  • new acellular pertussis vaccines, either with more antigens or an adjuvant
  • a new live attenuated nasal vaccine, BPZE1
  • new whole-cell vaccines with reduced endotoxin contents (so should have fewer side effects that then original whole-cell pertussis vaccine – DTP)

Before you get too excited, keep in mind that none of these vaccines will be available in your pediatrician’s office any time soon. Developing a new vaccine takes a lot of time.

BPZE1 has started phase 2a trials though.

What do we do until we get new pertussis vaccines?

“We should be more vigilant than we have been in the past to recognize and treat pertussis in all age groups so that transmission to young infants is reduced. Most important (although not discussed in this review) is to ensure that all pregnant women receive the Tdap vaccine between 27 and 36 weeks’ gestation with each pregnancy. Also, we should consider routinely administering Tdap vaccine every 3 years to all adolescents and adults who were primed with a DTaP vaccine.”

James D. Cherry on The 112-Year Odyssey of Pertussis and Pertussis Vaccines—Mistakes Made and Implications for the Future

We should keep using the pertussis vaccines we have!

Vaccines work, even when they aren’t as effective as we would like.

More on Making a Better Pertussis Vaccine

Are You Ready for DNA Vaccines?

Believe it or not, vaccines aren’t a one-size-fits-all kind of a thing.

“There are several different types of vaccines. Each type is designed to teach your immune system how to fight off certain kinds of germs — and the serious diseases they cause.”

Vaccine Types

In addition to live vaccines, like MMR, there are inactivated vaccines, toxoid vaccines, and subunit, recombinant, polysaccharide, and conjugate vaccines.

Are You Ready for DNA Vaccines?

Vaccines made with current technology have helped save millions of lives.

It’s time for some new approaches though, especially as we are seeing the limitations of some of our current vaccines, especially the seasonal flu vaccine.

“DNA vaccines take immunization to a new technological level. These vaccines dispense with both the whole organism and its parts and get right down to the essentials: the microbe’s genetic material. In particular, DNA vaccines use the genes that code for those all-important antigens.”

NIH on Vaccine Types

While a DNA vaccine might sound like something out of the 23rd century, researchers have been studying them since the 1990s.

“Researchers have found that when the genes for a microbe’s antigens are introduced into the body, some cells will take up that DNA. The DNA then instructs those cells to make the antigen molecules. The cells secrete the antigens and display them on their surfaces. In other words, the body’s own cells become vaccine-making factories, creating the antigens necessary to stimulate the immune system.”

NIH on Vaccine Types

Does the idea of being injected with the genes for a microbe’s antigens scare you?

“The original concerns associated with the DNA platform were the potential for genomic integration and development of anti-DNA immune responses. Exhaustive research has found little evidence of integration, and the risk for integration appears to be significantly lower than that associated with naturally occurring mutations”

Ferraro et al on Clinical Applications of DNA Vaccines: Current Progress

What do you think happens when you get the flu?

The flu virus and it’s DNA is taken up by your cells, and those cells then start making more flu proteins.

“This approach offers a number of potential advantages over traditional approaches, including the stimulation of both B- and T-cell responses, improved vaccine stability, the absence of any infectious agent and the relative ease of large-scale manufacture.”

WHO on DNA Vaccines

So where are all of the DNA vaccines?

“However, the results of these early clinical trials were disappointing. The DNA vaccines were safe and well tolerated, but they proved to be poorly immunogenic. The induced antibody titers were very low or nonexistent, CD8+ T-cell responses were sporadic, and CD4+ T-cell responses were of low frequency. However, these studies provided proof of concept that DNA vaccines could safely induce immune responses (albeit low-level responses) in humans.”

Ferraro et al on Clinical Applications of DNA Vaccines: Current Progress

After getting disappointing results in the 1990s, researchers have since moved on to second-generation DNA vaccines, which are being tested for HIV treatment and prevention, Zika, Dengue fever, influenza (DNA vaccine prime), HPV, cancer treatment (metastatic breast, B cell lymphoma, melanoma, prostate, colorectal), chronic hepatitis B treatment, chronic hepatitis C treatment, herpes, and malaria.

There are many completed trials for DNA vaccines.
There are already many completed trials for DNA vaccines.

While many of these DNA vaccines are now in phase I and II trials, unfortunately, that means we are still a long time away from having a DNA vaccine on the immunization schedule.

More on DNA Vaccines

Vaccine Fast Tracking

Like a few other vaccines, Gardasil underwent Fast Track approval by the FDA.

“This is the first vaccine licensed specifically to prevent cervical cancer. Its rapid approval underscores FDA’s commitment to help make safe and effective vaccines available as quickly as possible. Not only have vaccines dramatically reduced the toll of diseases in infants and children, like polio and measles, but they are playing an increasing role protecting and improving the lives of adolescents and adults.”

Jesse Goodman, MD, MPH, Director of FDA’s Center for Biologics Evaluation and Research

But that doesn’t mean that any corners were cut in getting it quickly approved or that the vaccine isn’t safe.

Vaccine Fast Tracking

The Fast Track process can help get new drugs and vaccines approved more quickly by the FDA because they have:

  • more frequent meetings with the FDA to discuss the drug’s development plan and to help ensure the collection of appropriate data needed to support drug approval
  • more frequent written communication from the FDA about such things as the design of the proposed clinical trials and the use of biomarkers
  • eligibility for Accelerated Approval and Priority Review, if relevant criteria are met
  • a Rolling Review, which means that a drug company can submit completed sections of its Biologic License Application (BLA) or New Drug Application (NDA) for review by FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. BLA or NDA review usually does not begin until the drug company has submitted the entire application to the FDA.

In very simple terms, it is kind of like having a VIP pass at an amusement park. It gets you a guide and helps you jump to the front of many of the lines, but you still don’t get to operate the rides yourself.

Vaccine fast tracking doesn't mean that a vaccine gets approved too fast.
It is a myth that vaccine fast tracking means that a vaccine gets approved too fast.

Which vaccines have had Fast Track approval?

They include Gardasil, Vaxchora, a cholera vaccine, the MenB vaccines, and FluBlock, the flu vaccine that is made in insect cells.

Others that have Fast Track designation include vaccines for  anthrax (NuThrax anthrax vaccine adsorbed with CPG 7909 adjuvant), chikungunya, Clostridium difficile (Clostridium difficile toxoid vaccine), malaria, RSV, Zika, Ebola, Invasive
Staphylococcus aureus infections in surgical populations, Shigella (Flexyn2a), and Lyme disease. None are approved yet though.

And that all of these vaccines have Fast Track designation is a good reminder that it isn’t a guarantee of approval.

“With Fast Track designation, early and frequent communication between the FDA and the biopharmaceutical company is encouraged throughout the entire drug development and review process to help to quickly resolve any questions or issues that arise, potentially leading to an earlier approval and access by patients.”

Encouraging Vaccine Innovation: Promoting the Development of Vaccines that Minimize the Burden of Infectious Diseases in the 21st Century

It just puts them on a Fast Track to get approved if they meet all of the FDA requirements for safety and efficacy.

The ability to develop and approve new vaccines quickly is also important as we continue to face new emerging disease threats. Faced with a deadly global pandemic, everyone will be glad that we have the ability to Fast Track vaccines and other drugs.

More on Vaccine Fast Tracking

Which Vaccines Do You Get When You Join the Military?

The oral adenovirus vaccine is approved to prevent adenovirus infections in military populations.

Believe it or not, many vaccines are available that we don’t routinely get.

Some we only get if we travel, like vaccines for yellow fever and typhoid. Others we only get in high risk situations, like if you get exposed to a bat with rabies.

And one, the adenovirus vaccine, you can only get if you join the military.

Which Vaccines Do You Get When You Join the Military?

But don’t folks get a lot of vaccines when they join the military?

It depends…

Whether you join the Army, Navy, Air Force, Marine Corps, or Coast Guard, health personnel will evaluate your immunity status by checking your titers to routine vaccine-preventable diseases. So no, if you were wondering, it doesn’t seem like they just check the vaccine records that you might bring from your pediatrician.

And then once they assess your immunization or immunity status, you will get vaccinated:

  • upon accession – adenovirus, influenza, meningococcal, MMR, Tdap, and chicken pox
  • during the first or second half of collective training – hep A, hep B, and polio (if needed, although a dose of IPV after age 18 is required) and other vaccines based on risk

So, in addition to getting caught up on all routine vaccines that they might be missing, there are other “military vaccines” that they might need, including:

  • Adenovirus vaccine – given to enlisted soldiers during basic training
  • Anthrax vaccine – only military personnel with extra risk, although some civilians can get this vaccine too
  • Smallpox vaccine – only military personnel who are high risk and smallpox epidemic response team members, although some civilians can get this vaccine too

Which vaccines you get in the military might be determined by where you are getting deployed to.
Which vaccines you get in the military will likely be determined by where you get deployed.

Like the recommendations for civilians, other vaccines are mainly given to military personal if they have extra risk based on where they are being deployed.

  • Cholera – only military personnel with extra risk based on deployment or travel to endemic areas
  • Japanese encephalitis – only military personnel with extra risk based on deployment or travel to endemic area in Eastern Asia and certain western Pacific Islands
  • Rabies vaccine – pre-exposure vaccination is only for military personnel with animal control duties or with extra risk based on deployment, including special operations personnel
  • Typhoid vaccine – only military personnel with extra risk based on deployment or travel to typhoid-endemic areas and other areas with poor sanitation.
  • Yellow fever vaccine – only military personnel with extra risk based on deployment or travel to yellow-fever-endemic areas in sub-Saharan Africa and tropical South America.

These are the same vaccines that we would get if we traveled to high risk areas.

Military Vaccines in Development

It shouldn’t be a surprise that the military does research on infectious diseases and vaccines.

Members of the military are often put at great risk for known and emerging diseases, like Ebola, Zika, and malaria.

That’s why some vaccines might have been given as an investigational new drug in special situations, typically when “individuals who have a high occupational risk – laboratory workers, facilities inspectors, vaccine manufacturers and certain military response teams.”

These vaccines, which were initially developed at US Army labs, are no longer being produced, but have included:

  • Argentine hemorrhagic fever (Junin virus) vaccine
  • Chikungunya fever vaccine
  • Eastern equine encephalitis vaccine
  • Q fever vaccine
  • Rift Valley fever vaccine
  • Tularemia vaccine
  • Venezuelan equine encephalitis vaccine
  • Western equine encephalitis vaccine

Today, the Walter Reed Army Institute of Research (WRAIR) “is a leader in global efforts against the world’s most pervasive and high impact infectious diseases.”

WRAIR is working on vaccines for HIV, Ebola, MERS, and Zika.

What to Know About Military Vaccines

You will need some extra vaccines when you enlist in the military, but how many will depend on if you are up-to-date when you join and your area of responsibility. So there is no one-size-fits-all military immunization schedule.

More on Military Vaccines