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The science of vaccines

By Shannon Lee

The term “vaccine” was coined in the late 18th Century from the Latin word root “vacca,” which translates to “cow.” Why? The first of such inoculations involved an exposure to cowpox to help protect against smallpox. If you look up definitions for “vaccine,” you will encounter a cadre of medical terminology. To understand the current vaccine conversation, it seems appropriate to explore those terms, review the immune connection, and look at the standard process of vaccine development in our country. The human immune system is a mixture of interacting cell types that travel through the body in response to invasions by a pathogen (virus, bacteria, parasite). The initial, critical determination is whether this invader is truly foreign and not part of the body. The ability to distinguish between “self ” vs. “non-self ” is the hallmark of a properly functioning immune system. Autoimmune disorders are a breakdown in this feature. Pathogens give off signatures (antigens), chemical and structural identities that are very specific. Your immune cells cue in on these antigens to help identify the specific invader. If the body has been invaded by this pathogen before, then the cells recognize the antigen and initiate a response by calling up specific antibodies that will label the pathogen with a “kill this one” sign. Other immune cells rush in and dispatch the pathogen. If the body has not been previously invaded by this pathogen, then the immune system will go to work attacking as best it can, but may become overwhelmed by a rapidly reproducing pathogen. The good news is that although one may be sickened by this initial infection, the body will remember the pathogen in order to mount a quicker specific response if it’s encountered again in the future.

Immune memory can be developed in the body through natural exposure to a pathogen or through the inoculation/vaccination process. In terms of the immune system, the end result is the same: the body develops a specific memory response (including antibody production) to that pathogen. Whether through vaccination or natural exposure, the longevity of memory varies from pathogen to pathogen.

Early vaccinations involved inoculating a patient with small amounts of the live pathogen, or of a closely related pathogen (as in the cowpox example). Over time, the development of vaccines has become more refined, selecting for more specificity, safety, and less potential for disease manifestation caused by live pathogens. As such, there have been many different types of vaccines used. Some are a “killed” form of the target pathogen; some are portions of the pathogen that still contain the antigen signal; some are highly-concentrated antigen. The newly approved COVID vaccines are all mRNA-based; mRNA are short-lived, small, single- stranded portions of genetic material. These vaccines are part of a new, highly targeted class of vaccines that have been the subject of theory and research for more than a decade.

To develop these mRNA vaccines, researchers isolated the protein information from the spikes on the coating of the virus. Once they had the protein info, they synthesized the recipe copy— just a backward sleuthing process. When you receive the vaccine, the mRNA (recipe) is simply read by your ribosomes and the protein is produced. Because this protein mimics something foreign (i.e. the spike antigen of the virus), your immune cells go to work building a memory specifictoSARS-CoV2.ThemRNA then degrades, just like normal.

As an emerging new virus, SARS-CoV2 was only identified formally in late December 2019, and yet, the entire sequence of the genetic code was made available to scientists worldwide inside of a month. This rapid cooperation allowed for a grand effort of tremendous speed and collaboration to race toward the development of a vaccine. Together with government assurances (purchasing agreements, financial backing, etc.) made by nations across the world, the global scientific community was primed to embark on a research, development, and testing campaign with a fervor and speed that we’ve never seen before.Enlisting knowledge gained from several other pandemics (notably COVID and HIV), researchers were able to come up with multiple vaccine candidates and get them through the approval process inside of a year. This is truly astonishing when most vaccines have required five to ten years to be developed, and some epidemic diseases have no vaccine many decades later. Vaccine development and approval in the United States goes through a standard process: Exploratory, Pre-Clinical, Clinical Development, Regulatory Review and Approval, Manufacturing, and Quality Control. The critical first step (Exploratory) is the correct and specific identification of the pathogen. Pre-Clinical involves vaccine development and laboratory testing. Clinical Development involves actual people and has phases. Phase I is small groups of individuals receiving the vaccine; Phase II is a larger, more detailed trial; Phase III then expands to thousands of individuals taking part in a carefully controlled double-blind experiment (placebo vs. vaccine). The results of these phase trials enter a review process, which involves scrutiny by an independent and impartial panel of experts. The final two steps—Manufacture and Quality Control—are self-explanatory, but in the case of the COVID vaccine rollout in the United States, permission to manufacture on a grand scale prior to review completion was another way that the vaccine was fast-tracked. Additionally, as early as spring 2020, Emergency Use Authorizations were approved as part of the declaration of a national health emergency. These EUAs allowed the FDA to approve use of a new vaccine to be given widely to the general public. The first COVID vaccine to be approved for use came from the German biotech company Pfizer. Close on its heels, the Moderna (USA) vaccine was approved. These are the only two vaccines currently listed for approval by the Centers for Disease Control. Looking to get the vaccine? Remember to follow the recommendations of your healthcare providers, as some individuals may not be recommended for vaccination due to underlying health concerns or previous allergic reactions. Also recognize that your adaptive immune response does take some time (1–2 weeks) to build a memory to the antigen—you are not super-human right after your second dose!

Shannon Lee, PhD, is a Glen Ellen resident and has been a science educator for 20 years. This special science column was written in early January 2020. Vaccine development and approval is a swiftly changing situation, so the information is dynamic. A variety of official reliable sources including the Centers for Disease Control ( cdc.gov) was used for research.

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