The plague, is one of the most notorious infectious diseases of all time, having a history or decimating populations with a 100% mortality rate. It is now understood that the plague is caused by Yersinia pestis, a Gram-negative bacterium, which is often transmitted through fleas to rodents and then to humans. The originally contracted bubonic plague could then develop into either septicemic plague or a pneumonic plague. There are currently no FDA approved vaccines against plague, and thus this paper, focuses on a novel approach, using a mutated bacteriophage T4 nanoparticle as a possible carrier of a vaccine, specifically targeting pneumonic plague.
This strategy utilizes two antigens, the F1 and V antigen, both of which assist in the immunosuppressive capabilities of the plague by helping Y.pestis to escape phagocytosis. Hence, by introducing these antigens through a vaccine, the immune system could ideally develop targeted antibodies which could fight off the bacteria in the future. The main problems with current F1 vaccine attempts are the effectiveness of cell-mediated immune responses and the fact that F1 naturally polymerizes into aggregates, which become unrecognizable from the normal form. The researchers of this paper attempted to solve these problems through their development of a novel delivery system, using the bacteriophage T4 nanoparticle. In order to form this nanoparticle, first the F1 antigen was mutated so that it no longer polymerized, and it was then fused to the V antigen, creating a F1mut-V immunogen which was further fused to the Soc protein on the phage T4 nanoparticle capsid. The infused T4 nanoparticle was then tested against isolated V, the F1mut-V, and then a control group in mouse studies with 12 mice per group. There were also other antigens tested, such as YscF and F1mut-V10, however these results were not as significant compared to the previously noted antigens.
Overall, the data showed that the utilization of the T4 nanoparticle caused the production of similar amounts of IgG1 antibodies, a part of the humoral response, than the soluble V and F1-V. However, the T4 mice were found to have higher levels of IgG2a, which is a part of the cellular response. This could be seen in the results as where as there were two deaths in both the V and F1-V groups, there was 100% protection with no deaths in the T4 group, which suggests that even though the antibody levels were similar, the antibodies in the T4 group seem to be more effective, meaning that the T4 antigens were more potent. All 12 mice in the control group died by day 4.
Overall the advantages of the T4 vaccine could be summarized as it enhances vaccine potency compared to the introduction of both isolated and combined antigens, as shown by the increased protection in the study results. Additionally, it the T4 vaccine would not require an additional adjuvant, and it could be easily be modified to include additional antigens as well. These findings are essential for the world because of the capability of aerosolized Yersinia pestis to be used as a bioterror agent. Y.pestis is both easily manufactured and aerosolized, and as a result of its 100% mortality rate within 3-6 days, it has the potential to be used as a lethal biological weapon. Thus, although relatively low amount of people die from the plague worldwide, this vaccine has the potential to eliminate the potential global threat.
By: Harris Allen