Kennedy · Proceedings of the National Academy of Sciences of the United States of America 2018 · narrative review · n=6 cases

Why the evolution of vaccine resistance is less of a concern than the evolution of drug resistance.

Cited 154 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review and theoretical synthesis evaluating six historical cases without systematic review methodology (Level 5 by design analogy)

PubMed 30559199 · doi:10.1073/pnas.1717159115 · record verified 2026-08-31

What was done

The authors conducted a comparative review of evolutionary dynamics between vaccine resistance and antimicrobial drug resistance, examining six putative cases of pathogen evolution in response to vaccines.

What was found

The abstract reports no quantitative metrics or statistical values. Qualitatively, the authors found that vaccine resistance is harder to detect, harder to confirm, and has less understood mechanisms compared to drug resistance; however, in all six reviewed cases, substantial health benefits of vaccination persisted.

Why it matters

This framework clarifies evolutionary differences between vaccines and antimicrobial drugs, arguing that vaccine resistance is less clinically threatening and informing the design of evolution-resistant next-generation vaccines.

Limits

The conclusions rely on a small, narrative sample of six cases rather than a systematic review. The abstract does not specify which six pathogens were evaluated, provide quantitative outcome measures, or report formal criteria used for case selection.

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