Q&A: Tales from the front lines of vaccine research at the NIH

Julie E. Ledgerwood, DO, always knew she wanted to become a researcher. She followed this dream all the way to the NIH. In 2002, as an allergy and immunology fellow there, Dr. Ledgerwood and her colleagues vaccinated a large number of troops at the Walter Reed National Military Medical Center and fielded questions about vaccination schedules, adverse reactions to vaccines and more. This experience sparked her interest in clinical vaccine research. She is now the deputy chief of the clinical trials core in the National Institute of Allergy and Infectious Disease’s Vaccine Research Center, where she oversees clinical trials on vaccines for a variety of viruses including HIV, influenza, SARS and West Nile.

In this edited interview, Dr. Ledgerwood shares some of the research her team is doing, what primary care physicians need to know about vaccines, and what she thinks the vaccine landscape will look like in 10 years.

What are some of the contributions you and your team have made to the body of medical research?

Our research primarily focuses on developing preventive HIV vaccines, improving influenza vaccines and developing of new vaccines for influenza and emerging infectious diseases such as SARS, West Nile, Ebola and malaria. We have published some important findings on influenza vaccine development. We have shown that a gene-based vaccine can improve the response to traditional influenza vaccines by sixfold. That was published in Lancet Infectious Diseases in 2011. That’s probably our greatest accomplishment.

Earlier, we showed that a gene-based vaccine for West Nile virus can induce neutralizing antibody. It’s the first DNA vaccine to induce neutralizing antibody in humans. Gene-based is the next generation of vaccine development. It is a descriptor that means you have decided that the antigen, the component of the infectious agent that your immune system needs to see, can best be expressed by the gene. So we actually encode that antigen on the gene and we give that gene to your body, which expresses it transiently, then your immune system sees it. It’s more reproducible. A manufacturer’s ability to create it is more dependable and rapid, and the responses to the vaccines are more predictable.

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Are gene-based vaccines in use?

No, they’re all investigational in humans. But there are licensed gene-based vaccines for animals.

Are you involved in the research that goes into the flu vaccines that we get every year?

Scientists at the WHO [World Health Organization] and the CDC [Centers for Disease Control and Prevention] lead the effort in choosing vaccine strains for the coming year. The flu vaccines we get each year are based on established technology that has been used for decades. Each year the CDC and the WHO establish the predicted strains for the coming year, and then all the vaccine manufacturers use those strains to develop their licensed vaccine using egg-based technology. There are a few exceptions to that. There are a few vaccine manufacturers who have established new methodologies for making vaccines, but those vaccines still would have to be made each year based on predicted strains. So that work is primarily done by epidemiologists and the WHO and the CDC.

What’s a typical workday for you?

I manage a group of about 25 clinicians and scientists and support staff. A lot of my responsibilities are in management, education, planning for upcoming clinical trials, conducting ongoing clinical trials, analyzing both safety and immunology for ongoing trials, and reporting on those findings. I spend a lot of time working with my team of clinicians to make sure that the subjects in our clinical trials are safe and that the trial’s being conducted per protocol. The bulk of the rest of my time I spend analyzing safety data, analyzing immunology data, planning new trials and reporting on trials.

There’s also a large education component because what we do is so unique. We have collaborators and community organizations that help us because we need to enroll the public. There’s a tremendous amount of education involved in what we do. We educate health care professionals, scientists and the public.

What should primary care physicians know about vaccines that they might not right now?

There is always a tremendous amount of vaccine clinical research going on around you, even if you don’t realize it. The phase I, phase II and phase III trials that are ongoing right now in this country and other countries will impact you years from now. As an example, when the HPV [human papillomavirus] vaccines became available everybody became knowledgable about them. But the vaccines had been studied in more than 30,000 women all around us before anybody really was talking about it.

Vaccine research is always ongoing, and that’s how the vaccines become licensed. Just be aware of it and know that the people who are in the studies are probably your patients. These are healthy people for the most part who volunteer for vaccine clinical research all over the country. Your patients may be involved in clinical trials, so you should just understand what that means.

Regarding HIV vaccines, one important point for practitioners is that there are 17 countries that have been or are currently investigating HIV vaccines in healthy populations, including the U.S. HIV vaccine testing is unique because when investigational HIV vaccines are administered, they induce antibodies to HIV. Those antibodies can cross-react with the test that people get when they are screened or tested for HIV. Physicians test by looking for antibody because there is no licensed vaccine, so the test is pretty reliable. But if the person’s been in an investigational vaccine study, then a test that looks at antibody is no longer sufficient to diagnose HIV. It will be a rare problem practitioners will have to deal with, but they should at least be aware of it.

What do you see for vaccines in the next 10 years?

I think important progress will likely be made for influenza. Currently, influenza vaccines must be made each year based on the prediction of strains that will circulate. There’s a lot of effort in the research community to develop what are called universal influenza vaccines, and that would be a vaccine that would protect against multiple strains, potentially for multiple years. The goal is to have a vaccine that can be administered less frequently than once a year, maybe every few years, and would protect against more than a couple strains, which current vaccines are not able to do.