Use of the Microparticle Nanoscale Silicon Dioxide as an Adjuvant To Boost Vaccine Immune Responses against Influenza Virus in Neonatal Mice

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