Vaccines for multidrug resistant Gram negative bacteria: lessons from the past for guiding future success

FEMS Microbiol Rev. 2021 May 5;45(3):fuaa054. doi: 10.1093/femsre/fuaa054.


Antimicrobial resistance is a major threat to global public health. Vaccination is an effective approach for preventing bacterial infections, however it has not been successfully applied to infections caused by some of the most problematic multidrug resistant pathogens. In this review, the potential for vaccines to contribute to reducing the burden of disease of infections caused by multidrug resistant Gram negative bacteria is presented. Technical, logistical and societal hurdles that have limited successful vaccine development for these infections in the past are identified, and recent advances that can contribute to overcoming these challenges are assessed. A synthesis of vaccine technologies that have been employed in the development of vaccines for key multidrug resistant Gram negative bacteria is included, and emerging technologies that may contribute to future successes are discussed. Finally, a comprehensive review of vaccine development efforts over the last 40 years for three of the most worrisome multidrug resistant Gram negative pathogens, Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa is presented, with a focus on recent and ongoing studies. Finally, future directions for the vaccine development field are highlighted.

Keywords: Acinetobacter baumannii; Klebsiella pneumoniae; Pseudomonas aeruginosa; antibiotic resistance; multidrug resistance; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Vaccines*
  • Drug Resistance, Multiple, Bacterial
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacterial Infections / prevention & control*
  • Humans


  • Anti-Bacterial Agents
  • Bacterial Vaccines