Influenza is Nothing to Sneeze At

Key Takeaways: 

• Influenza’s risks are often overlooked because people get used to a yearly threat  

• We need to prepare for increasing antimicrobial resistance with vaccines  

• Accepting a vaccine when we are healthy goes against our intuition, giving rise to vaccine hesitancy 

• Universal influenza vaccines are a long-term goal, not a current reality 

Rino Rappuoli, PhD, is fluent in influenza. 

The bacteriologist won the Albert B. Sabin Gold Medal in 2009 for a career that already included detoxification of the Bordatella pertussis toxin, plus additional work essential to vaccines against meningococcus C and pioneering the use of genomes to develop new vaccines (“reverse vaccinology”) that led to a vaccine against group B meningitis. 

His lifelong work in influenza — including the licensure in 1997 of a new adjuvant to improve the effectiveness of the seasonal and pandemic influenza vaccines — continues to be a top priority. Throughout a career that included leadership at GSK and Novartis and academic appointments at Harvard University and London’s Imperial College, Rappuoli says that “until COVID-19 came along, influenza kept me awake at night, because you know it’s going to be there every year.” 

We caught up with Rappuoli in his current role as Scientific Director at the pandemic research institute Siena Biotecnopolo Foundation (FBS) in Siena, Italy, where he continues developing influenza and other vaccines. “I started a long time ago,” he says, “and still the work is not finished.” 

What makes influenza so interesting? 

It’s there every year. Every year it’s going to kill people, make a lot of people sick, interfere with the workforce that has to stay home if they have children going to school. We need to be aware that an influenza pandemic can and will arrive, and we need to be prepared. 

What do you wish everyone knew about influenza? 

When things come every year like influenza, people start getting used to them and tend to forget to vaccinate. People should be aware that the risk is there every year. Unfortunately, we need a new vaccine annually because the virus continues to change, and we must update the vaccine to update our immunity. 

It’s not enough to say, ‘I got the vaccine last year’? 

It’s pretty simple. The virus that circulates for one season is not the one that will circulate during the next season, and therefore the vaccine needs to be updated. It’s more or less what we learned with the COVID vaccines. The initial vaccine against the Wuhan strain was perfect, 95 % effectiveness. But then the virus changed to different variants named B, alpha, beta, gamma, delta, and then omicron, and every variant was different and needed an updated vaccine. The new variants appeared pretty quickly with COVID, whereas that happens yearly with influenza.  

 What else are you working on? 

I’m a bacteriologist, so I’m also working on vaccines for bacteria that have become resistant to antibiotics. ‘Antimicrobial resistance,’ as it is called, is almost a pandemic — a silent one — because many bacteria are becoming totally resistant to any treatment. When these bacteria arrive, we go back to 120 years ago when there were no antibiotics. 

I’m working on some of these bacteria like Klebsiella, Shigella, Salmonella, and also mpox, which is becoming endemic in several African countries. We need to be prepared with vaccines. 

What emerging health threats keep you up at night?  

Seasonal influenza is pretty mild compared to what could happen with avian influenza. And right now, we have the virus in dairy cows in the United States. 

Why does the spread of avian influenza matter to global health? 

Avian influenza H5N1 was a virus that was only found in birds up until 1997. Now it is found in more than 50 mammalian species. In 24 hours, it killed entire colonies of sealions in Chile and Argentina. If that virus jumped onto humans with the same lethality, I’m scared we won’t be prepared. We do have vaccines, we developed them in 2007-2008, but they are basically for the virus that circulated at that time. They need to be updated. 

Are there updated vaccines for H5N1?  

There is one vaccine which has been updated, and which is available in small quantities. There are no large quantities. Some vaccine that was developed in 2006-2007 is stockpiled and while it is actually not perfect for the current strain, it has been shown to provide some protection. But I think if we really want to have complete protection, we need to update the vaccine and produce it in large scale. 

How long would it take to produce updated bird flu vaccines? 

To produce a seasonal vaccine, manufacturers start in April, and the vaccine is ready every year by the end of August. Because the manufacturing facilities are ready, the regulatory path is already there, vaccines can be produced in five months. But it requires a lot of work, concentration, and focus. 

Are scientists close to developing a universal flu vaccine?  

Well, that’s a dream I have had for the past 40 years. We made some steps in that direction because we have adjuvanted vaccines now and high-dose vaccines. Today, new technologies such as artificial intelligence can help us design better vaccines. We are not ready to develop a universal vaccine or get one shot and you’ll be fine for 50 years yet. But we’ll probably get to the point where you can vaccinate every two or three years. 

So, you continue to work on the influenza vaccine? 

Absolutely. I’m not alone. I have a team and a lot of collaborators. We work with the same goal. The race is between us and the virus. 

What would you want people to know about the influenza vaccine?  

The vaccines that we have are safe. That’s very important. We have now, I would say, 60 years of experience with influenza vaccines. Safety has always been paramount.
The other thing is that vaccines are needed. They are very important, especially for the elderly, where influenza can be dramatic and lead to death. Also, for young children, because while most of the time young children are healthy and can survive influenza, in some cases they can get very serious illnesses and risk their lives.  

Why is vaccine hesitancy increasing? 

There have always been people that were against vaccines. Back in 1796, when Dr. Edward Jenner started to use the cowpox virus to prevent smallpox, there were paintings where vaccinated people were portrayed with cows coming out of their mouth or ears. 

The reason is that vaccines are given to healthy people to keep them healthy. As humans, we are prepared to accept anything when we are sick, and we need medicines. But when we are healthy, accepting that we need an injection to keep us healthy goes against our intuition, against the way we think. That drives many of the fears about vaccines. 

Does that fear make it harder to talk about the benefits of vaccines?  

Being rational humans, we should understand the benefit of vaccination, and we should not risk getting a bad disease or risk our life. But we are also emotional humans, and unfortunately some take advantage of this to propagate fear of the vaccines. That is devastating because they are exposing people to needless risks. 

Did the COVID-19 pandemic increase vaccine hesitancy?  

The pandemic exacerbated hesitancy. Since the pandemic was very dramatic, people want to forget it, and they forget that vaccination saved millions of people from illness and death. Now we are in this post-pandemic moment where people don’t want to hear what happened during the pandemic. But it happened and may happen again. Actually, it will happen again. We should not forget, and we should learn from the past.