Why are pathogens rarely resistant to vaccines?

We have all heard the horrifying tales of incurable bacterial infections due to antibiotic resistance. But why don’t we see pathogens becoming resistant to vaccines? Intuitively, it seems that vaccines, like antibiotics, put selective pressure on pathogens. The selective force should drive the evolution of vaccine resistance, right? David Kennedy and Andrew Read explore this quandary in their recent publication in the Proceedings of the Royal Society.

Historically, when vaccine resistance arises, it takes much longer compared to antibiotic resistance. Vaccines created as early as the 1920s are still effective today while resistance to a new antibiotic can develop within a few years. Because the evolution of vaccine resistance is so rare, vaccines may be a solution to the drug resistance problems we face today. Vaccines reduce the need for antibiotic treatment and also decrease the number of cases and spread of infections.

Time between the introduction and development of resistance to antimalarials, antibiotics, and vaccines. An “x” indicates the emergence of resistance. Image credit: Kennedy and Read, 2017.

One of the first things that come to mind may be the difference between bacterial and viral infections. Antibiotics are used to treat bacterial infections but most vaccines work against viruses. Could it be the difference between bacteria and viruses that account for the scarcity of vaccine resistance? Short answer: no. Viruses become resistance to antivirals just as quickly bacteria do.

Kennedy and Read propose a two-pronged argument for why vaccines are less vulnerable to resistance than antibiotics:

(1) Vaccines act before infections occur.

A bacterial infection typically shows its true colors only after the bacterial cells have multiplied. More bacteria mean more symptoms. During an infection, the bacterial cells have plenty of chances to evolve. The larger a microbial population at the time of treatment, the more likely it is to evolve resistance to drugs. In the case of vaccines however, they are used before known exposure. Vaccines stimulate the immune response and prevent pathogen populations from reaching large sizes. Thus, by acting before a pathogen population grows, vaccines limit the opportunity for resistance to evolve.

(2) Vaccines target many structures of the pathogen.

Antimicrobial drugs tend to lose their effectiveness because they target one specific part of the cell. Any mutation in a bacterial cell that prevents it from being targeted will allow that cell to persist. Sometimes, all it takes is just one mutation. During treatment, antibiotics that target different bacterial structures are often used in combination. It is much harder to simultaneously evolve resistance to two antibiotics than it is for one. Vaccines work in an analogous way to this combination therapy. A vaccine can expose the host immune system to over a hundred components of a pathogen. Thus, the immune system possesses a huge repertoire of structures it can use to distinguish friend from foe. It is this vast array of targets that makes vaccines so much more invincible to resistance.

But vaccines aren’t completely untouched by resistance. There are a few cases where pathogens developed resistance to vaccines. The authors noted that these cases occurred because the vaccine lacked one or both of the characteristics described above. Resistance to the vaccine against the fish pathogen Yersinia ruckeri developed because it only targets one structure in the bacterium. Another example is the Gallid herpesvirus II that infects chickens. When chickens are vaccinated against this virus, they do not show symptoms but the virus stealthily replicates and infects other chickens. The viral population becomes tremendously diverse through repeated mutation events making it well equipped to overcome vaccines.

In the history of vaccines, we have seen examples of vaccines great and not so great. Understanding why pathogens do and don’t develop resistance to vaccines will help guide the creation of vaccines in the future.

CC BY-NC-ND 4.0 Why are pathogens rarely resistant to vaccines? by Jennifer Tsang is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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