mRNA and DNA Vaccines in Humans and Animals

Blog 3 of the 4 Part Series: Why I Want a COVID-19 mRNA Vaccine (and why you should too).

This is the third of four blog posts where I share what I have learned as a Tallahassee pediatrician doing my own research, and why I am excited to receive a COVID-19 vaccine:

  1. Last Sunday – How vaccines use our immune system to protect us against viruses, bacteria, and even cancer.
  2. Last Wednesday – How mRNA and DNA vaccines are different than traditional vaccines.
  3. Today – mRNA and DNA vaccine safety in animals and humans.
  4. This Wednesday December the 16th – Post Covid-19 Syndrome
The History of mRNA and DNA Vaccines

Starting around 1990, scientists were first able to inject genetic material (mRNA or DNA) into animal muscle AMD get the muscle cells to produce a protein based on this genetic material.  This laid the foundation for mRNA and DNA vaccines, which stimulate the muscle cells near the injection to produce the antigen for the vaccine.  So far, the biggest challenge with DNA and mRNA vaccines has not been safety but getting them to work.  Scientists have continued to tweak the antigen code and the adjuvant effect of the DNA and mRNA.  They have also discovered better ways of getting the mRNA or DNA into the cells. 

DNA and RNA Vaccines in Humans and Animals

Though the new COVID-19 mRNA and DNA vaccines will be the first fully licensed vaccines for humans, there have been DNA vaccines licensed for animals since 2002.  This includes vaccines for fish, dogs, cats, horses, and chickens.  None of these licensed vaccines for animals have had to be pulled from the market for safety or efficacy concerns.

mRNA and DNA Vaccines were already in Human Clinical Trials

Starting 10 years before the COVID-19 pandemic, mRNA vaccines had started entering human clinical trials.  This includes vaccines against influenza, rabies, cancer, Mono, and Zika virus.  In fact, Moderna had already completed a successful Phase 1 Clinical Trial for an mRNA influenza vaccine in 2017. Most of the mRNA vaccines in trials have been safe and effective, but just like traditional antigen plus adjuvant vaccines, some mRNA vaccines were not effective and some had too strong of an immune response.  But after a decade of conducting mRNA vaccine trials on thousands of human lives, results have been so good and promising that research and interest has continued to grow.

COVID mRNA Vaccines are 90-95% Effective, in Studies of Over 50,000 People

I am so impressed with reports of 90 to 95% effectiveness.  Yes, the Phase 3 Clinical Trials are just finishing, and we only have about 9 months of safety data in humans, but 95% efficacy is awesome!  First, many vaccines and medications get to Phase 3 trials just to find out that they do not really work.  Second, this is exceeding the CDC’s goal for 70% effectiveness (the seasonal flu vaccine is only 40 to 60% effective every year).  95% Efficacy means that if you give 100 people the COVID-19 mRNA vaccine, and then expose them all to COVID-19, only 5 out of the 100 would contract COVID-19!

COVID mRNA Vaccines have been Safe

So far, COVID mRNA vaccines have been safe.  About 1/3rd of people who received the Moderna or Pfizer/BioNTech mRNA vaccines had a reaction.  Normally a little redness or swelling at the injection site or mild aches or fatigue.  About 2% (2 out of every 100 shots) of study participants had a “grade 3” reaction, which means that the fever, body aches, fatigue, or swelling was severe enough to keep the person from doing his or her normal activities for a day or two.  There were no life-threatening “grade 4” reactions in with either mRNA vaccine trial.  This is similar to what people experience after a Tdap (tetanus-diptheria-whooping cough) booster vaccine.

What Other Adverse (aka Bad) Reactions were Scientists Worried About? 

Some scientists were worried about too strong of an immune response from the adjuvant part of the mRNA.  This could have led to high fevers, inflammation, damage of vital organs, or too much swelling at the injection site  Thankfully, even though the mRNA immune response has been strong (which is good because it stimulates the body to build antibodies), it has not been dangerously strong.  Again, the experience is similar to receiving a Tdap vaccine.

Second, scientists were worried about “Vaccine Enhanced Disease,” where the vaccine makes the real infection worse rather than protecting against the infection.  There were some animal vaccine studies of the 2002 SARS Coronavirus (which is similar to COVID-19), in which the experimental vaccine made the SARS infection worse, so scientists were appropriately nervous about VED occurring with COVID-19 vaccination.  Thankfully this has not happened. Even when vaccinated people get COVID-19, the COVID-19 infection has been less severe, instead of more severe.  More great news!

Third, DNA and mRNA are genetic material.  There is a theoretical concern that a DNA or mRNA vaccine could permanently insert foreign genetic material into our DNA, leading to health problems.  In the decades of DNA and mRNA vaccine experimentation, this has never happened in animal or human studies (but it could make a good movie).

In conclusion, the COVID-19 mRNA vaccines appear to be very safe and very effective, despite the rapid development and challenges of making a new vaccine.  Thankfully, mRNA and DNA vaccines had been in development for decades and were ready to be produced when the COVID-19 Pandemic hit.

I hope after reading this (long) blog, you are encouraged and excited about how our country can overcome this horrible illness.  Post with any questions, and read my next blog covering Post Covid-19 Syndrome.

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How mRNA and DNA Vaccines are New and Different

Blog 2 of the 4 Part Series: Why I Want a COVID-19 mRNA Vaccine (and why you should too).

This is the second of four blog posts where I share what I have learned as a pediatrician doing research, and why I am excited to receive a COVID-19 vaccine:

  1. Last Sunday – How vaccines use our immune system to protect us against viruses, bacteria, and even cancer.
  2. Today – How mRNA and DNA vaccines are different than traditional vaccines.
  3. This Saturday – mRNA and DNA vaccine safety in animals and humans.
  4. Wednesday December the 16th – Post Covid-19 Syndrome
What is the Difference Between mRNA and DNA?

Our genetic code is stored in a DNA “double-stranded” spiraling helix, made-up of 4 different DeoxyriboNucleic Acids, corresponding to the A, T, G, or C of our genetic code.  Think of DNA as our genetic code storage facility, and RNA (RiboNucleic Acid) as genetic copies that your body uses to make and do things.  RNA copies that are used to build things are called “messenger RNA” or mRNA.

Why Use mRNA (or DNA) in Vaccines if all You Need is an Antigen and an Adjuvant?

In my first post, I explained how a vaccine basically has two parts: an “antigen” (for COVID-19, usually the “spike” protein) and an “adjuvant” to stimulate the immune system.  Traditionally, vaccine companies make large quantities antigens and adjuvants and then package them into small vials for use.  In fact, 5 of the 11 COVID-19 vaccines in clinical trials are being produced just like this.  The problem is that takes a lot of time and money to design and build the manufacturing plants that safely and efficiently produce the antigen and adjuvant for a vaccine.   

Alternatively, mRNA vaccines (and DNA vaccines) use our own human cells’ built-in protein making ability.  The mRNA (or DNA) stimulates our own cells to make the antigen!  So instead of having to manufacture a new adjuvant and antigen for every new vaccine, scientists can simply alter the mRNA (or DNA) code so that a different antigen is produced by the cell.  And as an added bonus, RNA and DNA generally do not need added adjuvants, as they have built-in genetic code that triggers an immune response.

mRNA and DNA Vaccines Stimulate Cells to Make Antigens and Stimulate the Immune System to Make Antibodies.

In Summary, the mRNA in COVID-19 mRNA vaccines both stimulates human cells to make the COVID-19 spike protein AND stimulates the immune system to make antibodies against the COVID-19 spike protein. This saves both time and money, because scientists and engineers do not have to design and build manufacturing plants to produce large quantities of antigen and adjuvant. Instead, scientists can simply change the mRNA in a mostly ready-to-go system to rapidly manufacture a new vaccine.

In my next post this Saturday, I will review this history and safety of both human and animal mRNA and DNA vaccines. There will be a lot of good information! For example, did you know DNA vaccines have been licensed for use in animals since 2002?

I’m Nervous about Tweens and Teens getting easier access to Online Pornography with the Increase in Virtual Schooling

Dangerous websites, such as pornography, are just one Google search away from our children.

The exponential increase in children opting for virtual school will give children unsupervised access to the internet like we have never seen before. The computers that they will be using to access virtual classes and homework, give anyone access to anything on the internet.

And parents, including myself, don’t think that our eleven year-old would ever start looking at pornography. I mean, where would he or she get the idea? How would they know what to search for? And wouldn’t I find out?

But let me tell you, as a pediatrician and the parent of tweens, our kids are finding this stuff. In the exam room, many teenagers have confidentially shared what they have seen and watched online–and it’s not healthy. And not just teenagers but preteens as well!

And online pornography is dangerous for the mental health of our children, much like the pornographic magazines of the 80’s and 90’s, but even more so. There are many harmful effects of pornography on the childhood brain, and I will briefly review two here:

Online Pornography is Unhealthy

First, like a drug, Online Pornography is Addictive

Online pornography acts like a drug on our brain. Online porn scenes cause rapid and high levels of dopamine to be released into the brain. And just like a drug, teens who engage in online pornography will want more and more exposure to more and more provocative images, to experience this rapid and high level of dopamine release into the brain. This can lead teens to “waste time” on their computer, spend less time with their friends, and become lonely and depressed.

And recent research has shown that this effect is more pronounced on the teenage brain!

Second, Online Pornography can lead to Sexual Dysfunction

As adults, we know that pornography scenes are staged and fake, but children will take what they see as normal. This can lead to unhealthy expectations in their sexual encounters and can also lead to sexual dysfunction. And as “addicted” children watch more and more graphic pornography, they will have trouble with “normal” sexual function in a “normal” encounter.

What Can You Do? “CPR”

There is no perfect solution. If not at our own home, our kids may be exposed to dangerous websites at a friend’s home or on a friend’s device. But the best strategy consists of three tiered approach I call “CPR”:

  1. Communicate with your child about the dangers of the internet.
  2. Physically monitor potentially dangerous internet use.
  3. Restrict internet or device access to dangerous websites.
1. Communicate with your child about the dangers of the internet.

This is just like other important conversations that we will have with our children: sex, drugs, alcohol, and now add the internet. Depending on your children, around 9 to 11 years of age, I recommend sharing your views on the good and bad of the internet with your child. And if you don’t know what you believe, do some research. Read about how pornography, screen time, meeting strangers, etc. can all affect your child.

2. Physically monitor potentially dangerous internet use.

Most of the time, you can restrict your home internet or your child’s device from having internet browser (Chrome, Edge, Firefox, etc) access, but sometimes you can’t. If your child needs to access his virtual classes through a browser, then you have no choice but to allow internet browser access. But, you only need to allow them access to this device as necessary, and try to physically monitor what they are looking at. You cannot be there 100% of the time, but make sure that their device or computer is in a public area where you or other family members can easily see what they are doing. I strongly recommend against allowing a child to have internet browser access alone in their room.

3. Restrict internet or device access to internet browsers

It is much harder on computers and still very difficult on tablets and phones, but try to use parental monitoring software, like Apple’s Screentime, Google’s FamilyLink, or Disney’s MyCircle to completely block browser access. For example, with Apple’s Screentime, you can choose what apps your child has access to. If you really feel like they should be able to “browse” the internet, you can download child-friendly apps and browsers that allow you “whitelist” only certain websites that your child can visit.

Life with tech is tough

Technology has made our life better in so many ways, but it has definitely made it difficult to keep our children from being exposed to harmful material. Our parents had to make sure we didn’t have Showtime or HBO access as kids, but the internet is a whole new monster. And now that thousands of children will be spending thousands of hours online, we parents need to be proactive and protect our children. Our tween and teens will put up a fuss, but we need to do what is best for them.

Advocate for Change

One last thing we can do is advocate for our children. Ask your teachers and schools to include all their material in one internet location. For example, if a teacher requires a student to watch a video on YouTube, then you must leave YouTube unblocked, and your child will have access to anything on YouTube. But, if your school places all of their educational material on their own website or portal, then you can restrict YouTube access, protecting your child from potentially harmful material.

Children and COVID-19

As a pediatrician in Tallahassee, Florida, I have only seen a few cases of Coronavirus in children. I have had no cases of COVID-19 in my pediatric office, Canopy Pediatrics, and until the last few days, I had only seen a handful of COVID-19 cases while working in the pediatric ER for Capital Regional Medical Center (and these were mostly teenagers). Only one child was ill enough to warrant a hospital admission, and this child probably had a severe complication of COVID-19 in children called “Multisystem Inflammatory Syndrome in Children,” (MIS-C) which I will discuss further below. Since I am gathering information for an interview with WTXL TV to discuss how children are affected by COVID-19, I decided to share what I’ve learned here:

First, let me paint an overall picture of the medical effects of COVID-19 on children. Like adults, children infected with COVID-19 experience “flu-like” symptoms (some or all of the following): fever, cough, sore throat, congestion, runny nose, body aches, and sometimes vomiting, diarrhea, and abdominal pain. Sometimes they can develop a rash.

So far, COVID-19 infections in children seem to be less common, less severe, and less contagious in children than in adults. I say “seem” for two reasons: First, compared to adults, children have been much more socially isolated than adults (for example, most schools have been closed since March, but many adults have continued working or going to the grocery store), so better social isolation than adults is definitely one contributing factor to fewer kids being infected with COVID-19. Second, new information is always being discovered about how children are affected by COVID-19 in children.

Children Have Less Severe Infection

Regarding severity, reviews of children have found that about 15% of COVID-19 infected kids will be asymptomatic and 80% will have some mix fever, cough, and congestion without a low oxygen level (Flu-like symptoms), and less than 1% will need to be hospitalized. Compare this to adults, where 1% of adults aged 20-49, about 5% of adults aged 50-59, and 18% of adults over 80 years-of-age infected with COVID-19 will require hospitalization. So, kids generally do pretty well with COVID-19.

But, even though the average child has a less severe COVID-19 infection, very rarely, in about 1 in 300 COVID-19 pediatric cases, a syndrome occurs called “Multisystem Inflammatory Syndrome in Children” (MIS-C). MIS-C usually occurs 1 to 3 weeks after the onset of the child’s COVID-19 illness or can even occur after an asymptomatic infection. I hope MIS-C does truly occurs in 1 in 300 children infected with COVID-19, because for me personally, it has happened in 1 of about 10 children that I have seen with COVID-19. As the name implies, many systems of the body are severely affected. Symptoms include high and prolonged fevers; headache, confusion, or seizures; heart abnormalities; abdominal pain, vomiting, or diarrhea; and skin rashes, sore throat, and pink eye. And to make matters worse, most of these children have negative nasal swabs for COVID-19, but have positive COVID-19 antibody blood tests, meaning that MIS-C usually occurs as a complication towards the end or after an infection with COVID-19. Treatment for MIS-C is currently under investigation.

Children Seem Less Contagious

Children (especially prepubertal children) seem to be less contagious and become infected less often than adults. Children of all ages can still get a serious COVID-19 infection, but most of the evidence points to children generally being less contagious. In studies, young children (less than 10 to 12 years of age) have been less likely than adults to catch Coronavirus whether they are at home, at school, or just living life. On the other hand, teenagers with Coronavirus are probably just as contagious as adults and just as likely to catch the disease. Much of this information comes from comparing high schools, middle schools, and elementary schools in the same town and by looking at whom gets infected in a household.

There have been recent stories of outbreaks among children at camps, especially overnight camps. This reiterates that even if everything is done correctly, many children will still become infected with COVID-19. But it also reiterates that given the right (wrong) circumstances, like singing in groups or sleeping in a one room cabin with teenage counselors, COVID-19 will quickly spread from child to child.

Additionally, on July 30th, in a JAMA Pediatrics article, investigators found higher levels of COVID-19 viral RNA in children’s nostrils compared to COVID-19 positive adult noses. The clinical significance of this finding is yet to be seen. Many pediatricians think that since kids are not getting tested as much as adults (as many COVID testing sites will not test kids), the children in this study might have been more sick than the adults.

Why Are Children Less Affected?

So why is COVID-19 generally less severe in children than adults? Scientists are considering a few possibilities. One is that nasal tissue of younger children (less than 10 years of age) have less of the “ACE2” receptors that COVID-19 uses to enter into cells. A second possibility is that children have a less intense full body inflammatory response than adults. A third possibility is that children commonly co-infected with other viruses, and maybe other viruses are “running interference” leading to less COVID-19 virus production. And a fourth possibility is simply that children have relatively healthier blood vessels than adults.

How Are Different Ages Affected?

So, how are different ages of children affected? First, it does appear that children under 1 year-of-age, particular infants less than 3 months-of-age, are more susceptible to the effects of COVID-19 than older children. A few studies have shown an increased hospitalization rate in this age group. Also babies with Coronavirus may not have the typical fever, cough, and congestion of older children, but rather may present with trouble eating or fussiness.

Now the safest age to be right now is between 1 and 10 years of age. Many studies have shown that this age group is the least likely to get infected when exposed to COVID-19, the least likely to have serious illness from COVID-19, and the least likely to spread COVID-19 if infected. This may be because this age group has less ACE2 receptors than adults AND has a stronger body and immune system than an infant. But it is this age group that generally gets the severe MIS-C.

There is still some question as to whether kids over the age of 10 (tweens and teenagers) are less susceptible to COVID-19 than young and middle-aged adults. A few large studies, where large groups of people were swabbed, found similar rates of COVID infection in children 10-18 as adults. But, studies do show that teenagers are hospitalized less often than young adults. This could simply be that teenagers are less obese and have less chronic conditions than young adults.

So practically what does this mean?

First, for parents of infants or are pregnant: COVID-19 is more dangerous in babies than older children, so these parents should be extra careful to limit potential exposure to COVID-19, especially during the first three months of a baby’s life. These families should limit visitors and require that all visitors self-quarantine for 14 days before spending time with the baby. They can also limit the infant’s exposure to COVID-19 by finding a pediatrician who allows families to wait in the car (rather than a waiting room) or who provides home visits.

Second, for social interaction outside of school: Children, and their parents, are going crazy, not being able to interact with their friends and family. I think this data supports the idea that occasional close social interactions between toddlers or school-aged children (prepubertal kids) of different families (whose parents are otherwise being careful to social distance and do not have chronic conditions themselves), may be worth the risk for some families (as long as the parents keep their distance from each other). For many families, the low (but still substantial) risk of infection may be worth the trade-off for quality social interaction for their children. But again, the parents would need to practice good social distancing, so that they don’t accidentally infect each other.

On the other hand, close social interaction between kids over the age of 10 is more risky, which is too bad, because this is the age group that really needs social interaction. If kids of this age get infected, they will most likely do well themselves, but they are at high risk of passing the infection to siblings, parents, or other friends, which will lead to worsening of the COVID-19 outbreak.

And last, there is always the risk of a child developing COVID-19 Multisystem Inflammatory Syndrome in Children (MIS-C). As I mentioned earlier, scientists think it only occurs in 1 in 300 children infected with COVID-19, so hopefully my experience with MIS-C will not be the norm.

How Can Families Medically Prepare?

To be ready for this fall and winter, families need to have a pediatrician or family doctor that they can easily reach, and that they trust. When a child develops symptoms of a possible COVID-19 infection, this first thing to do is call or text your primary care physician for guidance.

And families can rest assured that Tallahassee has great emergency rooms and hospitals, like CRMC and TMH, that are prepared to evaluate their child in case of severe or concerning symptoms.