• Neonatal vaccination with BCG enhance spatial cognition and hippocampal plasticity. • Influenza vaccines enhance spatial cognition and hippocampal plasticity. • Combined vaccination with BCG and influenza vaccines showed synergistic effects. • Neonatal vaccination with BCG and influenza vaccines induced Th1 bias. Previous study has demonstrated the neurobeneficial role of BCG and influenza vaccines. Based on this, our study concentrated on the synergistic effects on development of central nervous system by combined vaccination with BCG and influenza vaccines in rats. Our results displayed that pups combinedly vaccinated with BCG and influenza vaccines showed a significant enhance in spatial cognition, induction of LTP, hippocampal neurogenesis and morphology of dendritic spines compared with pups vaccinated with BCG solely. Furthermore, combined vaccination with BCG and influenza vaccines showed higher expression of BDNF, IGF-1, IL-4, IFN-γ and lower IL-1β, TNF-α and IL-6 than BCG. Taken together, combined vaccination with BCG and influenza vaccines presented synergistic effects on spatial cognition and hippocampal plasticity in rats. [ABSTRACT FROM AUTHOR]