Influenza Vaccine Development


An expert panel discusses the development of recombinant and cell-based vaccines and new types of influenza vaccines being explored.

Rodney E. Rohde, PhD, MS, SM(ASCP)CM, SVCM, MBCM, FACSc: Dr Welch, one of the advances in influenza vaccines was the development of recombinant and cell-based vaccines. Please compare, if you would, egg-based vs cell-based vs recombinant influenza vaccines. What are the benefits and limitations, even with each one?

Adam C. Welch, PharmD, MBA, FAPhA: When you’re looking at an egg-based vaccine, you start with a candidate virus that’s determined by the FDA, the CDC [Centers for Disease Control and Prevention], and the WHO [World Health Organization]. They figure out what’s circulating in the Southern Hemisphere and they predict as best as they can what would be circulating in our upcoming flu season. They develop the strains of the vaccine. There are 4 strains that they put in there now with any quadrivalent vaccine. Then they have to replicate that. And the environment that will sustain life for a virus is a chicken egg. It has everything they need to replicate the virus. So they’ll do that. The problem is that process is time-consuming. They usually identify the candidate virus in February, and flu vaccines aren't ready to go until July, August, or September for the next flu season. Cell culture–based and recombinant vaccines add speed to that process. It allows the manufacturing process to be [nimbler], which is great for things like an H1N1 pandemic and even in general in any flu season. Having speed to market is a lot better for getting more people vaccinated, so that is one of the benefits of it. It also doesn’t rely on the health and quality of chicken eggs. If there’s a virus that infects the chicken population and eggs are contaminated [or] they’re in short supply, we can develop these cell-cultured, synthetically manufactured vaccines to help with the total supply of flu vaccine out there in the United States. So speed and relying on the egg supply are good things that come with this technology.

Rodney E. Rohde, PhD, MS, SM(ASCP)CM, SVCM, MBCM, FACSc: Good stuff. When I was starting my career, I worked for the Department of Health in Austin and a little bit with the CDC. I actually used to use cell-based [cultures] for diagnostics too, to grow flu virus. So it’s interesting over my 30-year career to see that, and even the understanding of the virus. I know when you interact with the public, one of the things I often talk to them about is [that] viruses are very host specific. So that need for a living host, a chicken egg cell, was forever until vaccines were starting to use….

Adam C. Welch, PharmD, MBA, FAPhA: Now they use mammalian cells to help produce some of that. And they have a different seed virus. So it’s come a long way now that we recognize there are 2 different manufacturing ways, multiple manufacturing ways that we can produce vaccines for use. The CDC’s stance is that we get people vaccinated. So preferentially, they’re looking at getting a vaccine as better than not getting a vaccine until we get to certain populations.

Rodney E. Rohde, PhD, MS, SM(ASCP)CM, SVCM, MBCM, FACSc: Dr Worz, there are many new types of flu vaccines being explored. How important is it to continue researching and developing new and improved versions of the flu vaccine? And you might even touch on, perhaps, the possibility of the ongoing hope for a universal flu vaccine.

Chad Worz, PharmD, BCGP, FASCP: I think Dr Welch did a good job of explaining all of the variables that go into how we create the flu vaccine, and how we try to address what strains might be coming in any particular flu season. And I think the pursuit of advances, whether it’s in the speed of manufacturing or in the ability to elicit a response, is going to always be a continual need for all of us as we try to hold back these flu pandemics or hold back these outbreaks of influenza. It’s why we have an annual vaccine. It’s why we go through this process year after year to try to get better and try to elicit better responses from people. In terms of a universal vaccine, I know they’re working on it. I would be hard-pressed to ever say, “Yes, we’re going to get the right answer for everybody.” I think one of the things we learned during COVID-19 and what we've learned in our experience is that people are different. We’re a diverse population. We’re starting to make decisions about age groups, about certain ethnicities in terms of how the immune system works. So I think a universal vaccine would be great. I know they’re pursuing it. There’s an opportunity, but it’s also difficult. We’re always focused on the adaptable part of the virus and trying to make sure that we’re eliciting a good response year after year to get deeper into that, and to get down to the stock of the virus. And to get something more universal is more challenging.

Rodney E. Rohde, PhD, MS, SM(ASCP)CM, SVCM, MBCM, FACSc: I totally agree. One of the important points…to make too is that as a virologist, not only are we looking at differences in people––the diversity in people, age, gender, whatever you’re talking about––but the virus. I generally tell people that RNA viruses are much more difficult to create a universal vaccine for than DNA viruses. RNA viruses just tend to mutate, especially influenza. Multiple subtypes come out each year. So it’s just an ongoing dilemma.

Adam C. Welch, PharmD, MBA, FAPhA: I think one of the issues also is the persistence of the protection from that 1 injection. We know that if you get an influenza vaccine now, you’re protected if you’re young and healthy, probably upward of about 6 months. If you are older, [and] you have some immunosenescence, for example, that protection may not be as long. So that’s one of the issues with vaccinating too early in flu season––…it doesn’t protect you from when the peak incidence of flu may happen, which may be as late as February or March or even later than that. We need that annual influenza to kind of boost that persistence in immunity each year so that we remain protected.

Rodney E. Rohde, PhD, MS, SM(ASCP)CM, SVCM, MBCM, FACSc: Yes, it’s really patient specific. When you think about it, I’ll sometimes talk to my students and my colleagues about the importance of maybe not jumping to that flu vaccine in September, but perhaps waiting until October or November, depending on the season of the year. One year you might need to start in September. In other years you may wait until November, again to help that coverage last into March, April, and May.

Randy McDonough, PharmD, MS, BCGP, BCPS, FAPhA: I think that’s why it’s important, though, why we need to be watching the literature and understanding it because that has evolved as well…. We used to say it only lasts for a certain number of months. We realized that it might be longer, but you’re right; for an older patient, [it] may not be. So when we look at our older patient population, maybe we should be getting it more in October, or late October, so they have that longer immunogenicity against the flu. It’s just interesting because I’ve been doing flu shots and vaccinations for a long time within my practice. And every year I tell my staff, we[‘ve] got to keep up with this; things change.

Rodney E. Rohde, PhD, MS, SM(ASCP)CM, SVCM, MBCM, FACSc: It’s a moving target.

Randy McDonough, PharmD, MS, BCGP, BCPS, FAPhA: It is a moving target.

Adam C. Welch, PharmD, MBA, FAPhA: And the unfortunate events of COVID-19 have also taught us and have been a case study in a lot of things. When people were social distancing, they were masking and were really mindful of contamination and spreading viruses; influenza rates went down as well. So those prevention strategies work for influenza as well. And RSV [respiratory syncytial virus rates] went down. So all these other upper respiratory infections tended to go down. But also people weren’t out there getting exposed to a small extent and boosting their immunity subclinically, so that the flu season, when everyone got back together, was a little bit earlier and the peaks were higher than they were before.

Rodney E. Rohde, PhD, MS, SM(ASCP)CM, SVCM, MBCM, FACSc: We certainly saw RSV make a vicious comeback last year.

Transcript edited for clarity.

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