Acute hepatopancreatic necrosis disease (AHPND) caused by pathogenic isolates of Vibrio parahaemolyticus (VPAHPND) carrying a plasmid encoding two pir-like toxins, is one of the most serious diseases affecting shrimp aquaculture. This study investigated if the microbial feed ingredient “Novacq™” improves resilience of Penaeus vannamei to VPAHPND infection and mortality. Two independent challenge trials were conducted where shrimp were fed a diet containing Novacq™ or a control diet for either 10 or 15-days (for trial 1 and trial 2 respectively) prior to exposure to VPAHPND. Mortalities were monitored every 3 h over the challenge periods (trial 1–99 h and trial 2–120 h) and foregut samples were collected from individual shrimp at different stages of the disease challenge to compare pirA and pirB toxin expression and V. parahaemolyticus abundance via qPCR. Shrimp fed Novacq™ had higher survival compared to control fed shrimp in both trial 1 and trial 2 with the relative percent survival (RPS) compared to the control 34% and 51% respectively. However, differences in Kaplan Meier survival estimates between the two diet treatments were only significant in trial 2. There was no significant difference in expression of pirA or pirB toxin genes or V. parahaemolyticus abundance between the two diet treatments in either trial, however, both toxin expression and V. parahaemolyticus abundance significantly changed throughout the disease time course. Results of this study along with previous studies of Novacq™ effects on a viral pathogen and other performance traits (i.e. growth), suggests Novacq™ may promote a general resilience phenotype that offers greater protection against both bacterial and viral agents of which the mode of action is still unknown.