Earlier this month, the Trump administration said it had concluded $500 million in mRNA vaccine research and shifted its focus to other approaches calling the previously announced “all virus” vaccine platform “Generation Gold Standard.”
“Generation Gold Standard is a paradigm shift,” Dr. Jay Bhattacharya, director of the National Institutes of Health, promoted the following research initiative in a May news release: “It extends vaccine protection beyond the limits of tension-specific, and uses traditional vaccine technology brought in the 21st century to prepare for the threat of the flu virus not only today but tomorrow.”
However, vaccine and infectious disease experts say this approach is misguided.
“That’s a bit of a step back,” said Dr. James Campbell, vice-chairman of the American Academy of Pediatrics committee. “We have been inactivating the entire virus vaccine for a very long time.”
The first whole virus vaccine was developed by Louis Pasteur in the late 1800s. Louis Pasteur created an early version of the rabies vaccine.
“It’s not revolutionary at all,” said Angela Rasmussen, a virologist at the University of Saskatchewan. “It’s actually something like ancient by vaccine standards.”
Other vaccines use certain proteins in the virus to activate the immune system, but whole virus vaccines usually maintain most of the virus’s components.
“We’ve seen a lot of trouble with our children,” said Dr. Paul Offit, director of the Center for Vaccine Education at Philadelphia Children’s Hospital. Other all-viral vaccines use live but weakened versions of the virus.
Campbell said in years of vaccine research, scientists were able to identify the parts of the virus that are most likely to activate the immune system and train them to combat invading pathogens. These parts are known as “antigens.”
When the immune system is like a bloodhound in the body and tracks invaders, many new vaccine technologies targeting specific antigens present a bloodhound with only fragments of the most useful invader clothing. Meanwhile, a whole virus vaccine is like presenting a bloodhound throughout the invader’s wardrobe.
Campbell said that while at first glance it might be better to use the whole virus rather than the whole virus, the additional portion of the virus may actually do nothing to improve the immune response.
“For example, the hepatitis B vaccine is a single antigen, the hepatitis B surface antigen, which provides almost 100% protection against hepatitis B. It does not require the entire hepatitis B virus,” he said.
Offit agreed. “The hepatitis B vaccine has effectively eliminated hepatitis B infection in young children,” he said. “That’s enough.”
Campbell provided the Covid-19 vaccine as another example. “We had a covid vaccine for the whole virus, but it wasn’t used in the US and was used elsewhere. Looking at the general protection from them, it’s not that good,” he said.
For example, a study from Singapore found that people who receive the entire virus vaccine are more than 1.5 times more likely to get infected than those immunized with an mRNA vaccine that targets only the viral spike protein.
“If you’re killed a whole virus vaccine for Covid, if you think it’s the perfect technology to move forward when the pandemic starts, we have it,” Campbell said.
There is no need to improperly deploy the entire virus vaccine when it is not necessary. In some cases, it can be harmful.
Campbell pointed to the development of the RSV vaccine as a case in which it was done.
“When we used the whole virus and killed the RSV vaccine years ago, it led to something called “Antibody-dependent enhancement,” rather than protecting children from RSV,” he said. “The kids had worse RSV than they hadn’t been vaccinated because they had a whole formalin inactivation virus.”
Its RSV vaccine trial was in the 1960s and regained research over decades.
Since then, he has said that RSV vaccinations have been directed only against F proteins, which are part of the virus, or that they have used monoclonal antibodies, such as preform immune responses. The first RSV vaccine was approved in 2023.
“They’re really well protected,” he said. “We don’t want to use a whole virus killing vaccine on RSV. It’s going to hurt people.”
Some viral vaccines are still in use. Hepatitis A and rabies vaccines kill the entire virus vaccine. That is, it contains the constituent fragments of the inactivated virus. Seasonal influenza vaccines also use all viral technology.
Campbell said a whole virus vaccine could be the best choice for some future pathogens.
Pursuing a universal flu vaccine
However, as suggested by the Department of Health and Human Services, whether the whole virus platform will unlock new innovations in the pursuit of a universal influenza vaccine, Campbell said that it is possible to use whole virus vaccines if they are genetically engineered to express multiple influenza strain antigens, but that is not of much use on all-tolerance platforms.
“If it’s just a virus and that’s one tension, that’s what we’re doing right now,” Campbell said.
HHS spokesperson Emily Hilliard said in a statement: “The Generation Gold Standard illustrates an important step in restoring a strategic focus and radical transparency on preparing for the US pandemic.”
“A BPL vaccine platform, fully developed by government scientists who are not affected by the industry, could provide broad, long-term protection against all influenza virus pathogens, including influenza and coronaviruses, blocking transmission at sources and halting the outbreak,” Hilliard said. BPL, or betapropiolactone, is a chemical that has been used for decades to kill the virus used in vaccines.
Universal influenza vaccines have been a long-standing goal for scientists as they ideally provide long-standing protection against influenza. Because of how quickly the virus is mutating, you need annual flu shots to protect you from the biggest strains.
“There are a lot of different paths where people work, especially if they can’t make a universal flu vaccine, which is a very old technology that people have tried many times before, and I don’t think they’re putting all the eggs in one basket and actually moving the fields,” Campbell said.
Offitt said withdrawing research funding for mRNA vaccines could be particularly harmful in the event of a pandemic.
“If something bad happens, like there’s avian flu pandemic, for example, we’re not much prepared,” he said, adding that the production cycle of mRNA technology has an overall production cycle.
“We probably need a year to manufacture nationwide,” Rasmussen said using the entire virus vaccine.
Other vaccine technologies, such as protein subunits and mRNAs, “basically you just make a protein or mRNA and can do it synthetically without the need for a virus or anything to grow it,” she said. “It’s much easier to change and adapt as needed, as new strains can emerge.”
“One of the 22 studies eliminated in the $500 million withdrawal was considering how valuable mRNA technology would be for avian influenza.”
Ultimately, Campbell said that science should lead the way, not a top-down dicta that brings together scientists.
“The devil is in detail, not just a drastic statement about which platform is the right platform and which isn’t,” he said.
Multiple platforms are available for vaccine development, and each has been tested for its characteristics.
“In the end, you get up to look like one or two, perhaps the best, and those are things people continue to pursue,” he said. “That’s what we do with vaccines,” he says, “to try to figure out what works and doesn’t in both basic science, immunology, models of disease, before we enter humans, and in real human research.
