Safety, immunogenicity, and efficacy of NDV-3A against Staphylococcus aureus colonization: A phase 2 vaccine trial among US Army Infantry trainees

Vaccine. 2021 May 27;39(23):3179-3188. doi: 10.1016/j.vaccine.2021.04.031. Epub 2021 May 4.


Background: Military trainees are at increased risk for Staphylococcus aureus colonization and infection. Disease prevention strategies are needed, but a S. aureus vaccine does not currently exist.

Methods: We enrolled US Army Infantry trainees (Fort Benning, GA) in a phase 2, randomized, double-blind, placebo-controlled trial of NDV-3A, a vaccine containing a recombinant adhesin/invasion protein of Candida albicans that has structural similarity to the S. aureus protein clumping factor A. Study participants received one intramuscular dose of NDV-3A or placebo (adjuvant alone) within 72 h of arrival on base. Longitudinal nasal and oral (throat) swabs were collected throughout the 14-week Infantry training cycle. Safety, immunogenicity, and efficacy of NDV-3A against S. aureus nasal / oral acquisition were the endpoints.

Results: The NDV-3A candidate had minimal reactogenicity and elicited robust antigen-specific B- and T-cell responses. During the 56-day post-vaccination period, there was no difference in the incidence of S. aureus nasal acquisition between those who were randomized to receive NDV-3A vs. placebo (25.6% vs. 29.1%; vaccine efficacy [VE]: 12.1%; p = 0.31). In time-to-event analysis, there was no difference between study groups with respect to the S. aureus colonization-free interval (VE: 13%; p = 0.29). Similarly, the efficacy of NDV-3A against S. aureus oral acquisition was poor (VE: 2.4%; p = 0.52).

Conclusions: A single dose of NDV-3A did not prevent nasal nor oral acquisition of S. aureus in a population of military trainees at high risk for colonization.

Keywords: Colonization; MRSA; Military trainees; Staphylococcus aureus; Vaccine.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Humans
  • Immunogenicity, Vaccine
  • Military Personnel*
  • Staphylococcal Infections* / prevention & control
  • Staphylococcal Vaccines* / adverse effects
  • Staphylococcus aureus
  • Vaccines*


  • Staphylococcal Vaccines
  • Vaccines