In March 2023 researchers at Tel Aviv University and the Israel Institute for Biological Research announced that they have developed an mRNA-based vaccine that is “100% effective against a type of bacteria that is lethal to humans”. With results published in Science Advances, the authors claim that although “a multitude” of mRNA vaccines are being designed and deployed against viral diseases or cancer, “bacterial pathogens remain largely untapped”. Thus, they investigated the potential that mRNA lipid nanoparticles (LNPs) present. 

mRNA-LNP meets plague 

The authors note that mRNA-LNPs are “clinically relevant, rapidly manufactured, and inherently modular”. These qualities were demonstrated during the COVID-19 pandemic, which emphasised the importance of the platform in “emergency preparedness”. 

The Gram-negative bacterium Yersinia pestis is well-known as the culprit of the infectious disease that has “claimed the lives of millions of people throughout human history”. Indeed, the authors recognise that “because of its lethality and infectivity”, it is “classified as a potential bioterror agent”. Despite this, antimicrobials have led to a decrease in morbidity and mortality, yet there is a pressing need to develop vaccines in the face of antimicrobial resistance.  

The paper suggests that “several” candidates confer protection in animal models and clinical studies, but none has been approved for use in “Western countries”. Thus, the research goal was to design several mRNA vaccine versions based on the F1 capsule protective antigen, evaluate the antigen-specific humoral and cellular responses in mice, and assess the protection effectiveness against a “fully virulent Y. pestis strain using challenge trials”.  

Attaining the unattainable 

Dr Edo Kon, first author, refers to the “great advantage” of mRNA vaccines, besides their “effectiveness”: “the ability to develop them very quickly”. 

“However, until now scientists believed that mRNA vaccines against bacteria were biologically unattainable.”  

The study demonstrates the opposite, Dr Kon says, with the results indicating that it is entirely possible to develop vaccines that are “100% effective against deadly bacteria”.  

“Our study demonstrates a rapid, fully protective mRNA-LNP vaccine against the lethal Y. pestis bacteria”.  

The authors hope that the platform can be “harnessed” for the development of effective vaccines against other bacterial pathogens. 

“These findings are of substantial relevance and immense importance, considering the global emerging crisis of antibiotic resistance and the lack of effective conventional therapies and vaccine candidates.”  

Professor Dan Peer of the Laboratory of Precision Nano-Medicine hopes that the study will “provide a pathway” for any bacterial pandemic threats that we might face in the future. 

Myriad mRNA benefits  

Compared to “traditional recombinant protein vaccines”, the mRNA-LNP vaccine platform has “several advantages”, according to the scientists. For example, mRNA vaccines are “highly versatile” and can be “rapidly manufactured and easily adjusted” to respond to variants of concern in pandemics.  

Another advantage is the induction of “both humoral and cellular immune responses”, which expands the “potential antipathogenic effect against pathogens” through “both intra- and extracellular life cycles”.  

Storage sensitivities 

As we have explored in previous posts, a “major limitation” for vaccines developed with mRNA-LNP is the “inherent instability of mRNA molecules”. Consequently, there is a requirement for “cold” or “ultracold” shipping and storage.  

For more about technological partnerships to combat these challenges, head to our technology section to read our posts. 

We will hear more about preparations for a bacterial pandemic and developments in mRNA technology at the World Vaccine Congress in Washington next month. To join us, get your tickets here.