The Search Continues: Coronavirus Vaccination Not “One-Size Fits All”

A number of the leading COVID-19 vaccines, including the first to market, rely on new platforms. These are technologies that have been developed over years, even decades, to target not just a single disease, but to take advantage of a key scientific development to affect a range of (current and future) clinical needs. Messenger RNA, which underpins the first two vaccine candidates is one such example – developed for other purposes and now deployed to combat a previously unknown virus.

At the Massachusetts General Hospital (MGH) Vaccine and Immunotherapy Center (VIC), we have been developing a self-assembling vaccine (SAV) platform that activates the immune system to attack specific targets. The core of the platform is a protein adapted from the bacterium that causes tuberculosis (called the protein core) and that powerfully displays fragments of proteins to the immune system. In our Self-Assembling Vaccine platform, any protein sequence from a new virus can be readily attached to the protein core to quickly make a vaccine. In 2014, for example, using Lassa virus, we went from viral sequence through pre-clinical testing in only 120 days. (Suffice it to say, that is fast!)

Knowledge of the immune response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2 or COVID-19) infection has been accumulating at an almost unimaginable pace. Dr. Patrick Reeves and his team at VIC, in collaboration with Voltron Therapeutics Inc., have developed a method for sifting through the knowledge and identifying the regions of the novel SARS-CoV-2 virus that the immune system targets most strongly. Each individual’s immune response is different, as indicated by the varying degree of illness that people experience once exposed to COVID-19. For this reason, rather than selecting a few precise sequences of the virus, Dr. Reeves and his colleagues chose an array of viral regions that appear again and again in different experiments. While a given individual may or may not respond well to a specific sequence within the region, most people’s immune systems will identify something within the pattern or grouping to which it will react in order to protect the person from the foreign invader – in this case, the coronavirus.

Will we need to vaccinate the whole world every year?

This next line of vaccines, like the SAV platform being developed by VIC, will prove to be very important. While the early reports and press releases from Pfizer, Moderna, and Astra-Zeneca are impressive and exciting, many unanswered questions remain. The first centers around durability of the immune response. More specifically, will we need to vaccinate the whole world every year? Unlike the front-running candidates, which are focused on stimulating antibodies in response to vaccine exposure, the SAV platform is aimed at training the T-cells (sometimes called memory cells) that are thought to provide longer lived immunity. T-cells are part of the adaptive immune system or active immune response; they recognize foreign substances, including infections, that they were exposed to in the past and then produce antibodies to attack the foreign body – kind-of like a precursor to or director of antibody production.

Regardless, second generation vaccines, like the one being developed at VIC, are critical for the overarching response

Next, there is the question of access and distribution of vaccines that require ultra-low temperature storage and multiple doses. Plus, safety concerns may emerge as follow up continues with ongoing trials. While rare and hopefully not serious, untoward side effects or adverse reactions could limit the number of people who should otherwise receive the vaccine. Progress thus far has happened at record speed; therefore, we dare to hope that the frontrunners will be enough to suppress or eliminate COVID-19 worldwide. Regardless, second generation vaccines, like the one being developed at VIC, are critical for the overarching response. In addition, the SAV platform can be applied to emerging infectious and other diseases where the immune system needs to be targeted, including coronaviruses in general, viral and bacterial infections, the next pandemic, and even cancer.

Written By Mark Poznansky, MD, PhD, FCRP, FIDSA  

Edited By Jacki Hart, MD