Bench to Bedside | May 2016

What It Takes to Become a Vaccine Champion: A Q&A With Paul Offit

Paul Offit, MD, director of the Vaccine Education Center at The Children’s Hospital of Philadelphia, isn’t your stereotypical scientific personality who prefers to stay behind the microscope instead of the limelight. Along with a talented team at CHOP, Dr. Offit invented a rotavirus vaccine that dramatically reduced the incidence of the disease in the U.S., following its approval and inclusion in the recommended vaccine schedule for babies in 2006. Back then, CHOP had about 400 admissions for rotavirus-induced dehydration in the hospital every year, Dr. Offit said, but now it is a rare event.

Dr. Offit’s career has evolved into being an author and vocal advocate for vaccine safety, childhood immunization, and stricter vaccine waiver requirements. He is the Maurice R. Hilleman Professor of Vaccinology and Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania.

Last year, Dr. Offit was inducted into the American Academy for Arts and Sciences along with the likes of journalist and novelist Tom Wolfe and singer-songwriter Judy Collins. He also joined the class of 2015 Fellows elected by the American Association for the Advancement of Science, which recognizes individuals for their contributions to science and technology. And the honors kept coming earlier this year when the University of Pittsburgh awarded him the Porter Prize, which honors an individual’s exceptional performance in health promotion and disease prevention.

His latest accolade was becoming a Vax Pack Hero, one of about 50 central figures who played roles in the history of vaccines and are featured in a new program created by the Vaccine Education Center. It consists of a web-based video game, trading cards, and an educational website designed to teach kids about how vaccines fight germs.

It’s easy to understand why Dr. Offit has a growing fan club, with his warm laugh, sharp intellect, and ability to speak with conviction. Yet, his outspokenness also has earned him a pile of hate mail that he admits is sometimes hard not to take personally. Read on to get more insights into why this vaccine champion is so passionate about protecting children and willing to take on the controversy.

How difficult is it to make a vaccine?

It’s really hard. Pretty much everything has to go right. It took 10 years to do the research to figure out which parts of the virus made you sick and which parts of the virus conferred a protective immune response. Then we constructed viruses that had the best of both worlds, which is to say that the vaccine wouldn’t have the proteins that were associated with virulence, but it did have the proteins that induced an immune response.

Our success involved a unique combination of talents among the three of us. The rotavirus vaccine wouldn’t have happened unless that team was in place at CHOP. We each brought something different to the effort that allowed it to become a vaccine. Stanley Plotkin, MD, was a veteran vaccine researcher. H. Fred Clark, DVM, PhD, was a brilliant scientist. Between the two of them, I was in the right place at the right time.

What do you see as your important contribution to the team?

Doing all the research and making the right strains was the easier part. The bigger hurdle was the research and development, working with a pharmaceutical company to do all those things you need to do to make a product. We constantly were meeting with the company to keep on track because vaccines are never big money makers. Vaccines are given once or a few times in one’s lifetime. They’re never going to be blockbusters. I was an NIH-funded researcher, but I also brought a personality that was persuasive.

Fortunately, there was somebody at Merck named Penny Heaton, senior director for vaccine clinical research, who ran that program and got it to completion. She was the star who ultimately helped us build the Phase 3 trial that was submitted to the Food and Drug Administration. You have to prove safety and efficacy before a vaccine is licensed. That was a prospective, placebo-controlled, 70,000-plus participant, 11 country, four year, $350 million trial.

From start to finish, how long did it take to create the vaccine?

It took 26 years. Once it was approved, the even harder part was implementation. Getting the vaccine into the developing world would never have happened without Bill and Melinda Gates. When they found out that rotavirus, which is a common cause of severe vomiting and diarrhea in infants, was the single biggest killer of young children in the world, they were willing to buy the vaccines at slightly above costs. Merck, to their credit, saw all their ethical and moral responsibilities to distribute the rotavirus vaccine. Two-thousand children a day die of rotavirus in the developing world, but it is lessening because of the vaccine; it probably saves hundreds of lives a day.

Why did you choose to pursue infectious diseases as a specialty, and what would you say to young physician researchers who are considering practicing in this area?

As a child, I was operated on for congenital club feet. I didn’t have polio, but I ended up recovering in a polio ward for almost two months back in the days when you would have one visiting hour a week. I saw those children in the polio ward as vulnerable, helpless, and alone. It’s still a vivid image. I think that wanting to protect children from harm is what drove me to pediatrics and why I wanted to help make vaccines.

There are always emerging viruses and bacteria, like Zika. There is much that we don’t know still and much for us to learn. It’s not just a matter of treating infections; we can actually prevent infections, and in addition, we can eliminate infections. Three infectious diseases have been eliminated from the face of the earth by vaccination: small pox, type 2 poliovirus, and a cattle disease called rinderpest. Infectious disease experts have the power to actually eliminate diseases. What other subspecialty can claim that?

Why did you establish the Vaccine Education Center?

The 26-year effort to make rotavirus vaccine taught me how difficult it was to make them and prove that they are what you claim them to be. When you claim that a vaccine is safe and effective, it must stand on a mountain of evidence. But at the same time, I realized that as very hard as they were to make, vaccines are very easy to damn. And so in the late 1990’s there was a concern that the combination measles, mumps, rubella vaccine caused autism, a concern that clearly was ill-founded and ultimately disproven. But it got an enormous amount of traction and still has traction. Then there was the notion that preservatives in vaccines could cause neurodevelopmental problems, including autism. That was also proven to be wrong but still hangs out there.

A lot of scientists weren’t weighing in on these issues. We were keeping our heads down and doing the science, but we didn’t feel the need to comment publicly. It’s not generally what scientists are trained to do or feel we’re good at. I think we all assumed other people were doing it, but they weren’t. So we created the Vaccine Education Center to try and explain the science of these issues to the public in a compelling manner.

Do you think the recent measles outbreaks in the U.S. also have helped to change how the public views vaccines?

As much as we’ve been talking for the last 15 plus years in our Vaccine Education Center to try and warn people that if they chose not to vaccinate, then they’re taking a much riskier choice, nothing educates like the virus. The outbreak that started in southern California at the beginning of 2015 and spread to 25 other states and into two provinces in Canada was a great educator.

You didn’t have to convince me to vaccinate my children. I had measles. I had mumps. I had German measles. I had chickenpox. I had those diseases. I know what they felt like. But my children didn’t grow up with these diseases; they don’t see these diseases today. For them it’s a matter of faith. The measles epidemic is a perfect example. In southern California, there were elementary schools where fewer than 50 percent of children in those schools were vaccinated. And then the measles outbreak hit, and those parents ran to get their children vaccinated. So fear sells. It’s too bad it came to that.

What do you think is on the horizon for vaccine research?

I think the next great wave of vaccines will be the pregnancy platform. Both the whooping cough (pertussis) and influenza vaccines are now required during pregnancy to protect both the child and the mother. I think that you will eventually see a Group B strep vaccine to protect the baby. You’ll see a respiratory syncytial virus vaccine, again to protect the baby. These are diseases that occur in the young child, including those less than four months old when it’s too young to get an active vaccine. A passive vaccine program essentially will be of value.

What gives you a sense of accomplishment in your current roles?

I love my role here in the Vaccine Education Center. My career will continue to focus on educating either by speaking or writing op-ed pieces or books. My most recent book, for example, Bad Faith, was about the 1991 measles epidemic in Philadelphia that centered on two fundamentalist churches. We had 1,400 cases of measles and nine deaths. That was unprecedented in the vaccine era. We watched those parents who chose not to vaccinate their children also chose not to seek medical care out of “respect for religion.” And that really upset me. There had been a law on the books allowing for religious exemption of vaccination for 10 years when that happened. What those parents were doing was perfectly legal. But when that outbreak hit, we got a court order to vaccinate them.

This book helped exorcise the demons, if you will, having lived through that experience. All of the money that was made from the royalties of the book went to a group called Children’s Healthcare is a Legal Duty, which has a mission to overturn the religious exemption from child abuse and neglect laws that exists in most states, which they recently did in Tennessee. That’s when you feel like you’ve done something. It’s all about child advocacy. I think each one of my books is about trying to protect children from harm. Again, it’s for the same reason that I wanted to make vaccines. Maybe I still see a little of myself as a child in that polio ward.


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Produced by The Children’s Hospital of Philadelphia Research Institute.

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