Table 2.

Vaccines lacking a known correlate of protection that failed efficacy trials

Target pathogen	Main affected populations	Main diseases	Correlate of protection	Vaccines failed in efficacy trials	Reference
P. aeruginosa	ICU, Surgical patients (elderly)	VAP, SSI	Not known	Vaccine failed in ICU setting	23
S. aureus	ICU, Surgical patients, patients with central lines, patients at risk of CA-SSTI (children and elderly)	CA-SSTI, SSI, VAP, BSI	Not established yet, potentially associated with functional Ab and T-cell response	4 vaccines failed to show efficacy against BSI and SSI	2–5
C. difficile	Subjects at risk of CDI	Diarrhea, colitis, pseudomembranous colitis, toxic megacolon, sepsis	Not established yet, potentially associated with anti-toxin Ab	A vaccine failed to show efficacy against colitis	NCT03090191
S. pyogenes	Children, the elderly, and patients with underlying medical conditions	Pharyngitis, scarlet fever, blood stream infection, rheumatic heart disease (RHD), pneumonia, necrotizing fasciitis, and Streptococcal Toxic Shock Syndrome (StrepTSS)	Not established yet, potentially associated with functional Ab	In the 1940’s a whole killed bacteria-based vaccine failed to prevent respiratory infections	24

ICU Intensive Care Unit, VAP Ventilator Associated Pneumonia, SSI Surgical Site Infection, CA Community Acquired, SSTI Skin and Soft Tissue Infection, BSI Bloodstream Infection, UTI Urinary Tract Infection, STD Sexually Transmitted Disease, CDI C. difficile Infection.