Universal Influenza Vaccine: Final Summary

25 pages plus bibliography and 47 sources (!!!) later, I have completed my paper! This research project has definitely been a learning experience for me, and in some ways it’s been very humbling as well. I had initially planned to produce a comprehensive review of all currently ongoing attempts to create a universal influenza vaccine, going into specific, biological detail about each method. I had intended to provide a brief overview of the influenza virus itself and the current seasonal influenza vaccine at the beginning of my paper, but to spend most of my time reviewing efforts to create a universal influenza vaccine, analyzing the pros and cons of each, and reaching a conclusion on how soon, if ever, a widely available universal influenza vaccine could reach the U.S. market. Unfortunately, I did not realize how ambitious this project truly was!  I vastly underestimated just how complicated the influenza virus is and how many current influenza vaccine types, both seasonal and universal, are on the market or in the works. I also didn’t fully realize how little I understood the makeup of the influenza virus, and how these many vaccines trigger the immune response in the human body, and how all of these different vaccines are created…etc. As a result, I spent way more time and energy than I had initially budgeted just getting to a point where I had the understanding necessary to research the many attempts to create a universal influenza vaccine. Since I spent so much time researching what I had previously thought of as simply “introductory material”, my paper turned into less of a detailed review of the possibility of a universal influenza vaccine and into more of a general overview of influenza and current and developing influenza vaccines. I was not equipped to produce as scientifically detailed a research paper as I had previously hoped, but that’s okay! This experience was immensely valuable nonetheless, because I was able to gain a deeper understanding of the influenza virus (a subject that has interested me for a while but I’ve never before had an excuse to really delve into) and the strategy of creating vaccines (an area that I hope to devote my career to). Even though my paper does not represent the sum total of what there is to know about influenza and a universal vaccine, I am proud of the work I have accomplished. I hope to use this knowledge I have gained through my Monroe project as a springboard for future, more detailed research about a universal influenza vaccine, now that I have the necessary underlying knowledge. Perhaps in one of my classes or during next summer I can pick one or a few of the many ongoing strategies to create a universal influenza vaccine and research it more in detail. I am really grateful for this experience because I got to sink my teeth into a topic that has always interested me, and I hope to continue this vein of work in the future!

There are many different universal influenza vaccine strategies currently in development. The methods that I discuss in my review paper include HA stalk domain strategies, M2e strategies (both of which I described in my previous post), T cell-based strategies, peptide strategies, and DNA strategies. T cell-based strategies rely on activating T cell immune responses in the body, thus allowing an initial round of infection to take place before triggering the appropriate cytotoxic T cell response. These vaccines are virus-vectored, just like the M2e vaccines, but they involve fusing conserved influenza virus proteins from the matrix 1 (M1) and conserved nucleoprotein (NP) coating to MVA, a weakened viral particle. This vaccine strategy has demonstrated protection against a variety of influenza A subtypes in mice, but they did suffer some weight loss as a result.

Peptide universal vaccine strategies are unique in that they trigger both B and T cell immune responses and provide protection against both influenza A and B subtypes, making them the most promising universal vaccine strategy in my opinion. I believe that the first universal influenza vaccine to hit the U.S. drug market will be Multimeric-001, a peptide-based vaccine that consists of an E. coli bacterial vector fused with HA, NP, and M1 peptides from both influenza A and B strains. It induced cross-strain immunity by triggering both B cell and T cell immune responses against H1N1, H3N2, and influenza B in a small human trial and has passed all safety tests, thus paving the way for larger human trials. Like other recombinant peptide and T cell vaccines, it can be manufactured quickly and can respond rapidly to pandemic-level demand, and has also been used as a primer for the seasonal trivalent influenza vaccine to boost immune responses in children and the elderly. Therefore, I think Multimeric-001 will be first be used in conjunction with the seasonal egg-based vaccine and then replace it entirely once all efficacy and safety checkpoints have been cleared.

DNA vaccines involve inserting a DNA plasmid containing gene sequences for one or more influenza strains to trigger antigen production in the body that will then trigger an immune response. While exciting, this technique is still highly experimental since the long-term effects of inserting foreign DNA into a host organism are still unknown.

Although there are no current universal influenza vaccines that have completed clinical trials and have been approved by the FDA, I predict that one of the techniques discussed here will have hit U.S. drug markets within the next decade. Many of these vaccine candidates are in the late stages of clinical trials and have demonstrated cross-strain protection against all or most types of influenza viruses in many different host systems, proving that a universal vaccine is far from impossible, which is encouraging news considering the fact that a novel influenza virus for which we have no other defense could arise in humans at virtually any moment.

Comments

  1. kllauritzen says:

    Hi Natalie! Your research sounds very detailed and it is evident that you put significant time and effort into writing your paper. I know we don’t completely agree when it comes to flu vaccines, but I still think that this is a topic worth researching and I think this was a great topic for you since you want to do something in this field. Also, your impressive use of terminology makes it clear that you know what you’re talking about and can explain this issue to other people in a concise manner. I think you did a phenomenal job and I hope to read your paper sometime. Maybe in the next few decades people will be getting the Caputo universal influenza vaccine! Great work!

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