Over the last couple of years, many scientists and epidemiologists have been watching the spread of a new virus, the H5N1 avian influenza. While initially developed in birds, there has just been a recent development where it has now begun to spread within populations of cattle, and even humans have now been infected. This new flu is extremely worrying as though the infected humans only seem to have mild symptoms, previous H5N1 epidemics have had severe mortality rates. Thus, scientists are currently looking for some possible vaccinations that work for humans and animals, should this virus become a major public threat.
One possible vaccine avenue that scientists are interested in studying is through the use of dual rabies virus vaccines or RABV that have been known to protect against other viral pathogens. To test this theory, a lab at Thomas Jefferson University developed a RABV-based H5 dual vaccine or RABV-H5 that has antigens which would protect against both the avian influenza as well as rabies virus.
In order to develop this vaccine, the researchers inserted a synthesized version of the avian flu into the genetic sequence of rabies virus. The proper functioning of both parts of the new vaccine sequence were then analyzed and confirmed that the vaccine sequence had effective functioning of both viruses and that the influenza sequence had successfully integrated into the rabies virus sequence.
Figure 1A.
Now that the vaccine had been made, the researchers wanted to determine how effective this vaccine was. The researchers tested the vaccine on mice using different methods to vaccinate them. They used both an inactivated, or killed, form of the RABV-H5 as the vaccine as well as a live version of RABV-H5 and vaccinated the mice either with an injection in the muscle or by applying droplets of vaccine to the nose.
Figure 1E.
After vaccination, the researchers looked for antibodies to the H5 which would serve as a sign that the vaccine worked and led to immunity of the virus. They found that in all cases, the mice had antibodies to H5 and found that vaccinating with a muscle injection at both the primary and secondary vaccination steps, the mice had higher antibody levels which indicates that these mice would have the strongest viral immunity.
After the success of the initial vaccination test, and following the same vaccination procedure paired with non-vaccinated control mice, mice were given a lethal dose of a mouse adapted version of the avian influenza virus. The researchers found that mice given the vaccine showed fewer signs of illness including weight loss and less virus seen on their lungs and had a much higher survival rate, including a one hundred percent chance of survival when given the vaccine intramuscularly both times or intramuscularly the first time and then a live version of the RABV-H5 vaccine delivered intranasally as a booster. This result stands in stark contrast to the mice that were unvaccinated and succumbed to the virus within six days, and even the mice that were vaccinated in alternate ways that only had a forty to sixty percent survival rate.
Seeing this success, the researchers did the exact same experiment, but this time with the authentic version of the avian influenza. Similar results followed from this experiment as vaccinated mice had a high survival rate and saw limited effects from the virus while unvaccinated mice succumbed to the virus at six to seven days.
With the success of the vaccine against both the mouse adapted version of the virus and the authentic virus itself, the researchers also wanted to look at how the vaccine would perform against a similar virus strain that is currently in circulation. The researchers found that the vaccine did seem to have some effect as it reduced weight loss in the vaccinated mice and led to high survival rates against a reduced form of the virus, but as the researchers expected, the vaccine had no effect on the lethal dose of the virus.
This paper illustrates the wide world of vaccines and the unlikely places that they can come from. The use of vaccine platforms such as RABV to build new vaccines in quick order so as to prevent disease spread should not be underestimated as these platforms most likely hold the key to preventing the spreading of emerging viruses and combatting viruses before they become a major human concern. The virus created and tested in this paper also offers a glimpse at emerging vaccine technology such as the ability to vaccinate for multiple viruses with a single vaccine and also shows the increasing need to develop vaccines with both humans and animals in mind to prevent a virus from spreading from animals to humans.
While this study shows a lot of exciting potential for vaccines against new and emerging infectious diseases, this study leaves open the future possibilities of this vaccine as the next steps would be evaluating its effectiveness in humans after the successes seen in mice. While there may be future viral threats that could begin a new epidemic, this emerging vaccine technology could help us to prevent that from happening.
Literature Cited:
Paran, N., Wirblich, C., Albrecht, R., Zabihi-Diba, L., Tarquinio, A., Kurup, D., Solomides, C. C., García-Sastre, A., & Schnell, M. J. (2026). Immunogenicity and efficacy of a rabies-based vaccine against highly pathogenic influenza H5N1 virus. Emerging microbes & infections, 15(1), 2620221. https://doi.org/10.1080/22221751.2026.2620221
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