
Why can’t the newer COVID vaccines kill off the disease like the Smallpox vaccine did? The Smallpox vaccine contains a live cowpox virus. Although a low risk for humans, it teaches your immune system, through exposure, to rally against pox-like viruses. But COVID vaccines can’t do that, and here’s why.
By David Stone
How Smallpox is Different and Why COVID Vaccines Can’t Have the Same Effect
The most important difference between the viruses, as pointed out by Forbes, is that SARS-CoV-2 — COVID-19 — “like most viruses, has animal ‘reservoirs.’ If public health efforts succeed at pushing it out of human populations, it will live on in fruit bats and ferret populations (at least), only to return to infect humans again.”
Smallpox does not have any animal reservoirs; so, it can’t mutate and re-infect humans.

Smallpox and COVID (Coronavirus) viruses are similar in that they cause serious, sometimes deadly disease. However, both diseases affect different types of cells.
- Smallpox mainly attacked skin cells called “epidermal cells”
- COVID primarily infects a type of cell called an airway epithelial cell.
Smallpox is a contagious disease that spreads from person to person through close contact. It causes a high fever, backache, chills and vomiting followed by a rash of small blisters. The disease kills about 30% – 40% of people who become infected. Mass vaccination of the human population eradicated Smallpox in 1980.
COVID, on the other hand, is not as contagious as Smallpox and does not cause such severe illness, but it can lead to pneumonia and, with immune systems weakened, other illnesses which are often fatal. Although the effect varies from country to country, COVID’s fatality rate is always well under 10%.
mRNA enters the picture
The Smallpox vaccine wipes out the disease because, when someone is vaccinated, they develop immunity to the disease. Immunity occurs when a person’s body produces antibodies in response to a foreign substance. The antibodies will then attack and destroy any of the viruses that enter the body.
Earlier COVID vaccines, using dead viruses, did not produce immunity. In fact, research showed that the vaccines actually increased a person’s risk of developing severe illness. mRNA vaccines proved the best solutions.
According to the federal Centers for Disease Control (CDC), to trigger an immune response, many vaccines put a weakened or inactivated germ into our bodies. Not mRNA vaccines. Instead, mRNA vaccines use mRNA created in a laboratory to teach our cells how to make a protein—or even just a piece of a protein—that triggers an immune response inside our bodies. That immune response, which produces antibodies, protects us from getting infected if the real virus enters our bodies.
Conclusion: Coronavirus Vaccines Can’t Match Smallpox’s Effectiveness
Smallpox is a contagious disease that spreads from person to person through close contact. It commonly infected the skin of humans where blisters called pustules form as a result of infection. Smallpox was eradicated in 1980 by mass vaccination. But COVID vaccines cannot be made with live viruses because they can cause serious illness and lead to pneumonia. With immune systems weakened, other illnesses raise the risk of being fatal.
Both Smallpox and coronavirus vaccines protect against potentially fatal infections; however, the Smallpox vaccine protects against a highly contagious disease and is made from a live vaccinia virus, a weaker version, while COVID vaccines are protective against various types of coronaviruses whether they are a single strain or a combination of more than one strain at a time. That’s necessary because coronaviruses freely mutate in the wild, giving birth to new strains. A prime-boost strategy is used to give initial protection and then boost that protection.
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