After over a year of worldwide shutdown due to the COVID-19 pandemic, the end appears near. Over 1.2 billion doses of vaccine have been distributed worldwide, including over 250 million in the United States. The pandemic is nowhere near over, however, and it is likely that COVID will never actually disappear but instead become endemic, like the flu. There are currently three vaccines authorized for emergency use in the United States, with another widely used in Europe and currently under Food and Drug Administration (FDA) review. Despite the encouraging progress on vaccination, many public health officials are concerned that the global vaccination effort is in a tight race against the potentially dangerous evolution of the SARS-CoV2 virus that causes COVID-19. After all, with more infections comes more opportunity for viral mutations. This post will discuss the available COVID-19 vaccines, the emerging variants, and what we know about the sustainability of immunity.
Background
In order to appreciate the differences among vaccines, an understanding of the “central dogma” of molecular biology is necessary. The central dogma summarizes how genetic information becomes functional molecules that impart function to a cell. The centra dogma is as follows:
DNA -> RNA -> Protein
DNA is the
genetic code of an organism – aside from random mutations, DNA is identical in
every cell in your body, and contains every gene that every cell may ever need.
What determines whether a particular cell is a skin cell or a liver cell or a
heart cell, for example, is the “expression” of particular genes. Gene
expression means the selective coding of particular DNA gene sequences as a
template to create RNA in a process called transcription. This RNA, known as
messenger RNA or mRNA, is then used as a template for a sequence of protein
building blocks in a process known as translation. Completed proteins then
carry out various functions that define the cell type. Figure 1 presents a
diagram demonstrating this process. DNA is much more stable than RNA or
proteins, which is why it serves as the permanent genetic template for every
cellular function in your body. RNA and proteins can be easily degraded and
therefore must be replenished to continue carrying out their functions.
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| Figure 1: The central dogma of molecular biology (Source: Khan Academy) |
Traditional
vaccines work by exposing the immune system either to the pathogen (disease-causing
virus or bacteria) itself or a surface protein from the pathogen that can be
recognized by the immune system to protect against the actual infectious agent.
The surface protein or protein segment recognized by the immune system is
called an antigen. The first two approved vaccines, by Pfizer-BioNTech and
Moderna, utilize a
new technology that relies on RNA instead of traditional methods. This RNA
strand contains the cellular instructions for an antigen of SARS-CoV2, the
spike protein, which helps the virus bind to cells. The other two broadly
available vaccines are by AstraZeneca and Johnson & Johnson. These vaccines
use
a viral vector (adenovirus) containing DNA coding for the same spike
protein (although the specific sequences may differ). The adenovirus
(which is not able to replicate) then injects individual cells with this DNA.
While use of viral vectors is also relatively new, unlike RNA vaccines they
have been used for previous outbreaks such as Ebola. Essentially, all these
vaccines work similarly by utilizing the molecular sequences that code for the
protein antigen, differing primarily by whether they rely on the DNA or RNA
step in the central dogma. All except Johnson & Johnson involve a 2-shot
regime. As stated above, DNA is much more stable than RNA, which is why the
two mRNA vaccines must be stored at freezing temperatures while the Johnson
& Johnson vaccine can remain indefinitely in a refrigerator.
