Neonates are at a high risk of infection, but vaccines are less effective in this age group; tailored adjuvants could potentially improve vaccine efficacy. Increased understanding about danger sensing by the innate immune system has led to the rational design of novel adjuvants. But differences in the neonatal innate immune response, for example to TLR agonists, can reduce the efficacy of these adjuvants in early life. We therefore targeted alternative danger sensing pathways, focusing on a range of compounds described as inflammasome agonists, including Nanoscale SiO2 (NanoSiO2), Calcium pyrophosphate dihydrate (CPPD) crystals and muramyl tripeptide (M-Tri-DAP), for their ability to act as adjuvants. In vitro these compounds induced an interleukin 1-beta (IL-1β) response in the macrophage-like cell line THP1. In vivo, adult CB6F1 female mice were immunised intramuscularly with H1N1 influenza vaccine antigens in combination with NanoSiO2, CPPD or M-Tri-DAP and subsequently challenged with H1N1 influenza (A/England/195/2009). The adjuvants boosted anti-haemagglutinin IgG and IgA antibody levels. Both adult and neonatal animals that received NanoSiO2 adjuvanted vaccines lost significantly less weight and recovered earlier after infection than control animals treated with antigen alone. Administration of the adjuvants led to an influx of activated inflammatory cells into the muscle, but little systemic inflammation measured by serum cytokines. Blocking IL-1β or caspase 1 in vivo had little effect on NanoSiO2 adjuvant function, suggesting it may work through other pathways than the inflammasome. Here we demonstrate that NanoSiO2 can act as an adjuvant and is effective in early life. IMPORTANCE: Vaccines can fail to protect the most at-risk populations, including the very young, elderly and immunocompromised. There is a gap in neonatal immunity between the waning of maternal protection and routine infant immunisation schedules, exacerbated by the failure of vaccines to work in the first months of life. One approach is to design age-specific formulations, with more effective adjuvants, based on our understanding of the nature of the neonatal immune response. We chose to target the inflammasome, a molecular complex capable of detecting infection and cell damage and of triggering IL-1β driven inflammation. We screened a range of compounds in vitro and in vivo and identified three lead candidates: NanoSiO2, CPPD and M-Tri-DAP. Of these, NanoSiO2 was the most effective and boosted the anti-influenza response in both adult and neonatal mice. This is important for the development of age-specific vaccines, designed using our knowledge of the neonatal immune response.