Not Your Granddaddy’s Vaccine: A Pregnancy and COVID-19 Perspective on Vaccine Technology

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The first vaccine consisted of fluid from cowpox blisters that Edward Jenner would scratch into patients’ skin to protect them against smallpox. This practice began in the late 1790s nearly a half-century prior even to the first successful use of the hypodermic needle, but it was a vast improvement on the earlier protective method: inoculation with blister fluid from smallpox victims themselves. Administered by lancing into a vein, pre-Jennerian smallpox inoculation saved lives, because the risk of dying of smallpox acquired through inhalation of droplets containing the infectious agent —variola virus— greatly exceeds the risk of dying from variola acquired through the blood or skin. Even so, the old methods carried some risk of death, often caused fairly severe smallpox disease, and overall were pretty messy. Thus, even prior to the advent of needled syringes to inject it in a controlled way, the smallpox vaccine —consisting of vaccinia, the causative virus of cowpox— represented a major advance. It worked because the vaccinia virus contains proteins on the surface of its viral envelope that are very similar to proteins on the envelope of the variola virus. These proteins stimulate the immune system to make antibodies against both vaccinia and variola, yet, in humans, vaccinia causes no more than mild symptoms. Consequently, recipients of the smallpox vaccine get the benefit of building the capability of the immune system to recognize and neutralize any variola virus that comes along without the disadvantage of being exposed to the actual causative virus during the immune learning period, the time before which the immune system is actually ready to fight off a smallpox attack.

I used the past tense above (recipients of the smallpox vaccine got the benefit), because this vaccine is not administered anymore (except for those in the military and those working with variola in the laboratory). That’s because smallpox vaccination was so successful that the disease was eradicated by the late 20th century. Since the 19th century, however, immunizations against other infectious diseases have come into use. We call them “vaccines”, because vaccinia —the cowpox virus used as immunization— comes from the Latin word vacca for cow. However, while they all teach the immune system to recognize and make antibodies against disease-causing agents, different types of vaccines use different tactics to achieve this effect.

Some of those tactics are fairly old. The old tactics include the smallpox tactic (use of a live, naturally-occurring infectious agent that is similar to the disease-causing agent but does not cause as severe a disease as the actual infectious agent), use of an attenuated, live agent (a form of the disease causing agent that does not infect human cells, yet it still stimulates the human immune system), and killing the disease-causing agent in a way that still leaves it capable of producing immune protection . Additionally, some commonly used vaccines have been developed against toxic agents that were never alive, but rather are produced by living agents; tetanus vaccine is an example of this category. However, the past couple of decades have seen vaccine production move into the realm of advanced biotechnology. This is an important consideration if you are pregnant, as pregnant women traditionally have been advised to avoid the live vaccines during pregnancy, but some of the newer technologies can lead to replacements for those vaccines. This perspective is also important for those pregnant in the COPVID-19 era, because (as of the writing of this post in mid-2020) there are a handful of vaccines against SARS-CoV2 (the virus that causes COVID-19), they all work with different tactics, and we don’t know yet, which ones will work the best. With this in mind, let’s glance at a couple of COVID-19 vaccines and the tactics that they employ for producing an immune response.

One vaccine that is in the news, because it is showing promise in pre-clinical (laboratory animals) and early human clinical trials is the Moderna vaccine. Also called mRNA-1273, the Moderna vaccine is what scientists call an mRNA vaccine. This means that business end of the vaccine consists of strand of what’s called messenger RNA (mRNA). In body cells, mRNA is like the middle person in a relay race. Genetic instructions encoded within small sections of the DNA of a cell are copied into strands of RNA, each with message corresponding to the copied DNA section. This RNA strand is called messenger RNA (mRNA) and typically a sequence of an mRNA molecule corresponds to a particular gene, although some processing happens after the mRNA is produced. Rather than reading your DNA directly, the machinery of your cells reads mRNA molecules to produce proteins that the instructions encode. Now, apart from mRNA, there are other types of RNA that are made with instructions from your DNA that do not carry instructions for making proteins, but they help with the process of creating those proteins. Using a universal language called the Genetic Code, your cells translate the particular message of each mRNA molecule to produce a particular protein. When it comes to vaccine production is that, because the Genetic Code is the same for everybody, your cellular machinery can make protein from any mRNA that gets into your cells, even if that mRNA has not been made from instructions in your own DNA.

In the case of the Moderna vaccine, scientists have created a little piece of mRNA that carries instructions for making a protein, called the spike protein, that the SARS-CoV2 virus displays on its outer surface. This is the protein that the virus uses the gain access to body cells by binding to a protein on body cells called ACE-2. Not only does this lead the virus to infect human cells, but by distracting ACE 2 from doing its job it causes a range of problems that occur with COVID-19 disease. However, by causing your own cells to make the SARS-CoV2 spike protein, your body introduces this protein to your immune system. The hope —and the implication of the laboratory animal studies— is that this will lead safely to immunity and more quickly and safely than if you had been injected with the spike protein itself, with a killed SARS-CoV2 virus, or with something else. As for safety in pregnancy, more study is needed, but since mRNA is a very indirect way of stimulating the immune system, most likely the Moderna vaccine will not prove any more dangerous for pregnant women than for anyone else.

Another vaccine strategy —this one underlying a few COVID-19 vaccines, including the well-publicized Oxford vaccine now going through clinical testing in the United Kingdom and showing promise— takes a virus called an adenovirus, and specifically type of adenovirus that infects chimpanzees, and alters it genetically. In the case of the Oxford vaccine, the adenovirus has been altered, so as not to be able to infect human cells, and also so as to express the SARS-CoV2 spike protein on its surface. This is what generates the immune response. Being a genetically modified virus, the Oxford vaccine is “live” in the sense that we apply “live” or “killed” to vaccines. However, since it does not infect human cells, this does not necessarily mean that it would be particularly dangerous during pregnancy. As with the Moderna vaccine, particular considerations for pregnancy require more study.

All of this is just a small sampling of where vaccine technology is headed, but clearly it is far in advance of that initial vaccine for smallpox that Edward Jenner created more than two centuries ago without any biological knowledge to guide him.

David Warmflash
Dr. David Warmflash is a science communicator and physician with a research background in astrobiology and space medicine. He has completed research fellowships at NASA Johnson Space Center, the University of Pennsylvania, and Brandeis University. Since 2002, he has been collaborating with The Planetary Society on experiments helping us to understand the effects of deep space radiation on life forms, and since 2011 has worked nearly full time in medical writing and science journalism. His focus area includes the emergence of new biotechnologies and their impact on biomedicine, public health, and society.

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