Researchers from Harvard T.H. Chan School of Public Health announced in 2023 that they had developed a new and “highly adaptable” vaccine platform with potential applications in the fight against viral pathogens. A study, published in Science Advances in January, details the “grave threats” posed to public health by viral pathogens. The authors emphasise that vaccination is the “most effective way to stop viral infections and their ensuing ravages”.
In their study, the researchers explored extracellular vesicles (EVs) to present viral membrane antigens for vaccine development. They report “unexpectedly” finding a way of making EVs.
“Our study established WAEVs (WW domain-activated EVs) as a versatile platform for delivering membrane protein antigens as vaccines for flu, HIV, and likely other human viral pathogens.”
Context of the study
A report on the university website states that a common problem with vaccines is that “the structure of the viral antigens they use may not be exactly the structure needed to kick the immune system into high gear”. The given examples are the viruses that cause the flu, HIV/AIDS, and COVID-19, which have antigens “embedded in a ‘lipid bilayer’”.
As many vaccines deliver antigens without this lipid bilayer, the resulting antibodies find it harder to secure themselves to and neutralise the virus. Thus, the researchers explored using the medium of EVs. According to Professor Quan Lu, these are “essentially squishy little balls encapsulated with a lipid bilayer”.
The group inserted flu or HIV antigens into EVs, testing them in mouse models of the diseases. They found that the mice that were given EV vaccines had “higher antibody production” and “significantly longer survival rates” than those that weren’t.
What does this mean?
The study demonstrated that “viral membrane antigens containing WAEVs induce robust production of antibodies that specifically bind to viruses”. For the flu virus in particular, immunisation of viral antigens on WAEVs “significantly reduced the lethality of the viral infection in mice”.
“These results demonstrated the utility of WAEVs in presenting and delivering a variety of viral membrane proteins in their native membrane-associated confirmation and established WAEVs as a highly adaptable platform for developing vaccines against viral pathogens”.
The benefits of WAEVs
Comparing WAEVs with existing vaccine platforms, the authors suggest “several potential advantages”. For example, with recombinant protein-based vaccination “substantial and challenging protein engineering” is required. WAEVs “bypass this obstacle” through the expression of viral membrane proteins on cell membrane. They are then loaded naturally onto the membrane of WAEVs during “vesicle budding in production cells”.
Furthermore, WAEVs are of “nonviral origin” and are less likely to be affected by existing or induced neutralising antibodies such as those that “hamper adeno-associated virus and other viral-based vaccination platforms”.
“WAEVs also may overcome some of the challenges existed for the state-of-the-art mRNA platform”.
They are “generally stable” and could address the “relatively labile nature of mRNAs”, thus reducing production, transport, and delivery costs. They also “may avoid the use of adjuvants”, which would further reduce the cost and possible side effects of vaccines.
A potentially powerful tool
Professor Lu believes the study showed that WAEVs “can serve as a novel, highly adaptable vaccine platform”, offering a “potentially powerful tool in our fight against viral pathogens”. Although the study was focused on flu and HIV viruses, he believes the system has applications against other viruses.
We will hear more about novel vaccine technologies with a range of applications at the World Vaccine Congress this April. If you are interested in joining us there, get your tickets today.