Universal Influenza Vaccine: Update 2

At this point, I have just about completed my research and I am beginning to convert my detailed outline into essay form. Hopefully I will have a finished product ready to submit in the next few days!

Through my research, I have learned that the human body fights off the influenza virus by recognizing the hemagglutinin antigens on the virus’s surface, thus triggering an immune response. The seasonal influenza vaccine works by mimicking a real infection. The influenza vaccine consists of purified, inactivated hemagglutinin antigens. When they are injected into the bloodstream, white blood cells engulf the antigens and “sound the alarm”, causing lymphocytes to produce antibodies. Antibodies come in an infinite number of shapes, and “fit” into only one antigen each, just like a key fitting into a lock. Once the body creates an antibody that binds perfectly to the hemagglutinin antigen, it replicates these antibodies so that they can recognize and bind to every viral particle in the body, marking them for digestion. After every viral particle has been digested and the influenza virus has been cleared from the body, a few antibodies hang around so that if the virus re-enters the body in the future, it can very quickly be fought off before it has time to take root. The seasonal influenza vaccine allows the body to create a stockpile of antibodies ready to stop a future infection in its tracks, without generating influenza symptoms.

Before beginning this project, I had been under the impression that there were only two forms of the vaccine: the inactivated inoculation and the live attenuated nasal spray. In fact, there are actually many different forms that the seasonal influenza vaccine can take. The inactivated quadrivalent seasonal vaccine (injection) and the nasal spray are made using an egg-based production process, but this process is very lengthy and can result in mutations of the vaccine virus due to the virus adapting to the egg environment. In addition, the process is completely dependent on the egg supply and thus cannot respond to sudden changes in demand, like in a pandemic situation. Some alternative production methods are currently available that present different advantages over the traditional vaccine, which I will discuss in more detail in my paper, but all of these alternative methods still have one issue in common: they need to be changed every flu season to reflect the currently circulating influenza viruses. A universal influenza vaccine would ideally only need to be administered once and would protect against all influenza strains, regardless of antigenic drift.

 

Efforts to create a broadly protective or a truly universal influenza vaccine target conserved proteins or components of the viral molecule that all or many different influenza viruses have in common. These conserved components include the stalk region of the hemagglutinin antigen (HA), the M2e component, the nucleoprotein, and the M1 component. Anti-influenza monoclonal antibody products that target the stalk domain of the HA have demonstrated promising results in animal clinical trials, but still require more efficacy testing in humans. Vaccines targeting the highly conserved M2e component of the influenza virus have demonstrated broad-range immunity in both animal and preliminary human clinical trials, though researchers have struggled to elicit a strong immune response using this method. To solve this problem, scientists have fused the M2e gene sequence to a viral vector and have also added HA to this recombinant virus-M2e vaccine as well, thus causing increased immune responses. I am still finishing up my research on the nucleoprotein and M1-based efforts, but each of the strategies I have mentioned here show promise.

Comments

  1. knmorrison says:

    Hi Natalie,

    The research that you have done so far sounds very interesting! I never knew that influenza vaccines are egg-based, I would think that by now we would be using more synthetic materials. Now that genetic engineering is so advanced, perhaps we can find some superior synthetic solutions to the problem of vaccine shortages.

    Given that the influenza virus replicates so quickly, I’m surprised that there are so many conserved components of the virus. It must have been difficult for researchers to determine which parts of the virus are conserved, given that there is such a wide variety of influenza strains! Of the components you have researched (stalk region of the hemagglutinin antigen (HA), the M2e component, the nucleoprotein, and the M1 component), is there one that seems most promising for creating a universal vaccine, or are they each useful in different ways?

    Good luck compiling your data, and I look forward to reading your conclusion!

  2. Hey Kayleigh!

    Yeah, I was very surprised as well at how antiquated the current vaccine manufacturing process still is. In my opinion, the most promising universal influenza vaccine is a peptide-based approach called Multimeric-001 that consists of an E. coli bacterium fused fused with HA, nucleoprotein (NP), and M1 peptides from both influenza A and B strains. This vaccine strategy has triggered both B and T cell immune responses against H1N1, H3N2, and influenza B viruses in small human trials, and can be manufactured quickly. M2e vaccines are also very promising since they have advanced so far in clinical trials, but they would only provide protection against influenza A viruses and therefore are not truly universal influenza vaccines.

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