Medicine / Vaccines / COVID-19

Universal Vaccine: Is It Possible for Coronavirus?

Could a single vaccine stop COVID-19 and future coronavirus outbreaks?

Jesse Smith is a medical student at the University of Minnesota Medical School. He is a former researcher in molecular biology and human blood development. His work can be followed on Twitter @deadlywarbler

Every year, millions of people voluntarily show up to clinics to receive flu shots. These vaccinations against influenza virus are a perpetual effort to tamp down influenza spread within human populations. Yet, despite this effort people are required to return year after year to be given repeat vaccines. The issue of diseases like the flu requiring repeate vaccinations has prompted researchers to examine the target of vaccines in search of what many are calling universal vaccines.

The reason behind why certain pathogens like influenza require repeat vaccination while others like polio only require one dose comes down to change. On the viral scale, change equates to mutation — changes to their genetic code that allows them to augment their structural makup on the protein level. Of the many different viruses, influenza is a master of change.

Other virus, like poliovirus do not elude vaccination in this way. It is not because poliovirus does not mutate, it surely does. The difference is that many of the mutations that occur in polio virus do not impart any specific biological advantage to the virus, and thus are lost to selective pressure. The result is a poliovirus that today closely resembles the virus that Jonas Salk encountered when he first developed a vaccine against polio in the early 1950's.

Vaccines have been a remarkable success in medicine, putting to waste diseases that plagued people for centuries. While, vaccines that requires annual dosing are still of immense value, they do pose problems from a public health perspective. Attending clinics to receive an annual flu shot requires time away from work, childcare or transportation — a luxury that not all people possess. Of course, there is the ever-present social resistance to vaccines that keep certain populations out of clinics during flu shot drives. All of these are factors that challenge vaccination levels. If a universal vaccine could be developed against a disease like influenza, you could theoretically remove this barrier to broad immunization.

And so, the hunt for a universal vaccine goes on, with labs around the world digging into the nuance of viral structure and life cycle to try to find aspects of these microbes that resist change. Targeting those structures could hold the key to a vaccine with wide ranging and long lasting effect. To understand this puzzle, you need to look closely at the structure of a virus.

Viruses like influenza or coronavirus are coated in a variety of surface markers. Many of these markers allow viruses to latch on to host cells, evade the host immune system, or to achieve the ultimate goal of injecting their viral genome into the host cell. These surface markers, being that they are on the outside of the viral structure are recognizable as foreign to the human immune system and thus elicit an attack by the host. During an initial infection from a virus like coronavirus, the host immune system works feverishly — pun intended — to curtail the infection while attempting to develop memory against the virus that will provide protection should it be encountered in the future.

Vaccinations work in the same way by eliciting an immune response without causing illness. Vaccines, in their many different forms, present those surface markers to the host immune system in an attempt to trigger the same immune response without causing the symptoms of an infection — what is known as a primary infection. However, if a new strain of virus emerges that expresses surface markers that the immune system has never seen before — be it from previous infection or immunization — then the host immune system will have to start from scratch in attacking this pathogen.

Viruses are haunting in their simplicity. They evolve on a scale many times faster that than of humans. They have the ability to rearrange their tiny genome to augment the structure of proteins and other markers on their outer structure. In doing so, they become virtually unrecognizable to an immune system, even from different strains of the same virus. Though most viruses adapt in one form or another, different viruses adapt at different rates. The rate of change in surface markers is the key to why some vaccines provide long-term immunity, while others only provide protection for a brief window of time. Because influenza is masterful at rearranging surface markers, we are required to constantly update flu vaccines from year to year to match current and potentially dangerous strains of the virus. So, you can see the potential power of a universal vaccine.

Technical sidenote: Two of the most notable surface markers for influenza are hemagglutinin (H) and neuraminidase (N). If you recall certain strains are referred to by these markers, for example Swine Flu is referred to technically as H1N1, where as one type of Avian Flu is referred to as H5N1. As far as the human immune system is concerned, the change from H1 to H5 makes this strain of flu essentially unrecognizable.

Universal Vaccines for Coronavirus

With this knowledge in mind, the current COVID-19 outbreak raises the question of whether universal vaccines for coronavirus are possible. COVID-19 is a novel virus to humans, but coronaviruses are nothing new. Coronavirus strains were responsible for the severe acute respiratory syndrom (SARS) outbreak in 2003 and the Middle East respiratory syndrome (MERS) outbreak in 2012. Each of these diseases was caused by a novel strain of coronavirus that emerged — as so many viruses do — from animal populations. Each new strain presented itself cloaked in surface markers that human immune systems have no memory of having ever encountered. Thus, outbreaks of novel infectious pathogens result in widely disseminated disease.

While efforts to develop vaccines that target the new surface markers — what are known as antigens (anti = against, gen = to produce) — are underway in the fight against COVID-19, there are teams of researchers looking into aspects of COVID-19 antigens that are conserved. Conserved traits are traits on COVID-19 that are shared by other coronavirus strains including MERS-Cov and SARS-Cov. Targeting these could theoretically provide protection not only against COVID-19, but virtually all strains of coronavirus. In the long term, a vaccine like this could be of immense value in curbing various forms of coronavirus-based diseases as well as protective against future emerging strains.

So, let’s dive into the coronavirus and see if a universal vaccine is possible.

In a previous article, I detailed the surface antigen, a protein known as spike. Spike proteins are the target for current vaccine development efforts. This protein gives coronaviruses the ability to latch on to host cells, thus initiating their invasion into the host cell. Coronavirus and influenza both express spike proteins their outer structure, though obviously in different form from one another. Spike proteins mutate rapidly, making them a moving target for vaccines and host immune systems.

For visualization purposes, imagine the spike protein as a head of broccoli, with a blooming outer head structure attached to a narrow stalk. In COVID-19, the outer head portion of the spike protein is responsible for binding to host cells, while the stalk is responsible for connecting the head to the body of the virus. The head region, while still performing the vital function for the virus, is constantly being mutated and assuming different configurations. The stalk region, on the other hand, does not mutate as readily. Similarly, the stalk region is conserved between various strains of coronavirus. Researchers have turned their attention to this region, theorizing that antibody production against the more conserved stalk region might be the basis for a universal immunity.

Labs at the Geisel School of Medicine at Dartmouth College and Vanderbuilt University Medical Center collaborated in 2017 to characterize the structure of the spike protein before it binds to a host cell. In this state, the spike protein exposes regions of the stalk as antigenic sites (Pallesen, 2017). Characterizing this structure could potentially allow vaccine developers to tailor the structure of vaccines such that the immune response includes these more conserved regions. This holds the potential for vaccines providing immunity against multiple strains — including future strains — of coronavirus.

Rather than focusing on one conserved region of the coronavirus spike protein, other researchers are focused on developing vaccines that introduce all of the previously known spike proteins antigens — those located on the binding sites on the spike protein head — to the human immune system. In this approach, the vaccine would include viral antigens from strains of coronavirus that cause SARS, MERS and COVID-19 bundles into one vaccine. Lumping of different viral antigens into one dose is not uncommon. Several of the vaccines we receive as children contain antigens from multiple different disease causing pathogens. However, not all viral antigens can be presented in the same way and elicit the same level of immune response needed to establish immunity. Some vaccines can include only antigens, while others need live or attenuated viruses to establish this response. This makes packaging, storage, trasnport and dosing of vaccines of this kind a challenge.

To overcome this, researchers have turned to nanoparticle technology to introduce vaccines containing multiple viral antigens. Nanoparticles are microscopic scaffolds on which any number of molecules can be attached. In terms of vaccines, nanoparticle design would involve a scaffold with antigens coating the surface of the particle. Nanoparticle-based vaccines do possess advantages over other forms of vaccines that include live or attenuated viruses. In designing nanoparticle-based vaccine against coronavirus, a scaffold could be developed that is studded with multiple antigens from known pathogenic strains of coronavirus.

In 2014, a group with the University of Maryland in conjuction with Novovax developed an experimental nanoparticle-based coronavirus vaccine shown to have immunogenic potential was developed against the SARS-Cov and MERS-Cov strains. In this case, researchers proved that nanoparticles containing coronavirus antigens were effective in developing antibody response (Coleman C, 2014). While this remains experimental, it is an important proof-of-concept in this type of vaccine design.

The quest for a universal coronavirus vaccine is still in the development phase. Vaccines of this kind could be years in the making. While the need for a rapidly developed COVID-19 vaccine — universal or otherwise — is desperately needed, the hunt for universal coronavirus vaccines remains an important area of research. Universal coronavirus vaccines holds the promise of not only curbing existing coronavirus outbreaks, but stopping them before they ever emerge.

Reference

Arnold C, 2017: https://doi.org/10.1038/nm1117-1248

Begley S, 2020: https://www.statnews.com/2020/03/09/coronavirus-scientists-play-legos-with-proteins-to-build-next-gen-vaccine/

Coleman C, 2014: 10.1016/j.vaccine.2014.04.016

Pallesen J, et. al, 2017: 10.1073/pnas.1707304114

Medical student, molecular biologist and educator. I write about science and medicine.

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