As the world reels from illnesses and deaths due to COVID-19, the race is on for a safe, effective, long-lasting vaccine to help the body block the novel coronavirus SARS-CoV-2. The three vaccine approaches discussed here are among the first to be tested clinically in the United States.
How vaccines induce immunity: The starting line
In 1796, in a pastoral corner of England, and during a far more feudal and ethically less enlightened time, Edward Jenner, an English country surgeon, inoculated James Phipps, his gardener’s eight-year-old son, with cowpox pustules obtained from the arm of a milkmaid. It was widely believed at the time that once milkmaids became ill with cowpox, a relatively mild disease, they were no longer susceptible to smallpox. The young boy became quite ill, but recovered in about a week. Jenner then injected James with material from a smallpox pustule and observed that nothing untoward happened. A new scientific approach to disease prevention was born.
A century later, it became clear that vaccination — a term Jenner coined from the Latin name for cowpox, Vaccinae variolae — worked because vaccines induce protective immune responses. We now know that vaccines can generate neutralizing antibodies by activating immune cells called B lymphocytes that secrete those molecules. Antibodies specifically recognize a shape on a virus or a toxin and bind to it, much like a key that tightly fits into a lock. They can then block the virus or toxin from binding to our own cells, effectively disarming it.
However, in order for these antibodies to bind strongly to viruses or bacteria and to last a very long time, the body has to be tricked into believing it is responding to an infection. When that happens, immune cells called T lymphocytes are activated and can help B lymphocytes make better, long-lived antibodies.
Seeking long-lasting immunity: Fragments and targets
Many weakened (attenuated) live viruses have been used as vaccines. These tend to provide long-lasting immunity even after a single dose. The yellow fever vaccine, for instance, generates immunity that can last a lifetime. Other examples include measles, mumps, and rubella combined (MMR), rotavirus, smallpox, and chickenpox vaccines.
Some vaccines are just killed versions of the whole virus. Immunity in response to such vaccines is not that long-lasting, and several booster shots are needed to enhance immune memory and prolong protection. The injected flu vaccine — a combination of strains of influenza most likely to circulate in a given year — is an example of a killed virus vaccine. Given as a single injection, it only offers protection for about three months. Other killed virus vaccines include those for rabies and the injected polio vaccine; both induce long-lasting immunity only when multiple doses are administered.
Many vaccines are made up of a piece, or a modified version, of the target virus or bacteria. Their effectiveness can vary, and booster shots are generally necessary to achieve relatively long-lasting immunity.