With concerns about the efficacy of repeat annual influenza vaccination, it is important to better understand the impact of priming vaccine immunity and develop an effective vaccination strategy. Here, we determined the impact of heterologous prime-boost vaccination on inducing broader protective immunity compared to repeat vaccination with the same antigen. The primed mice that were intramuscularly boosted with a heterologous inactivated influenza A virus (H1N1, H3N2, H5N1, H7N9, H9N2) vaccine showed increased strain-specific hemagglutination inhibition titers against prime and boost vaccine strains. Heterologous prime-boost vaccination of mice with inactivated viruses was more effective in inducing high levels of IgG antibodies specific for groups 1 and 2 hemagglutinin stalk domains, as well as cross-protection, compared to homologous vaccination. Both humoral and T cell immunity were found to play a critical role in conferring cross-protection by heterologous prime-boost vaccination. These results support a strategy to enhance cross-protective efficacy by heterologous prime-boost influenza vaccination.

The national EHDI 1-3-6 goals state that all infants should be screened for hearing loss before 1 month of age; with diagnostic testing before 3 months of age for those who do not pass screening; and early intervention (EI) services before 6 months of age for those with permanent hearing loss. This report updates previous summaries of progress on these goals by U.S. states and territories. Data are based on the Hearing Screening and Follow-up Survey (HSFS) conducted annually by the Centers for Disease Control and Prevention for the years 2006-2016. Trends were assessed using 3-year moving averages, with rates of newborns lost to follow-up or lost to documentation (LTF/D) also examined. During this period, the percentage of infants screened before one month increased from 85.1% to 95.3%, while the percentage receiving diagnostic testing before three months increased from 19.8% to 36.6%, and the percentage of infants identified with permanent hearing loss enrolled in early intervention (EI) before six months increased from 25.1% to 47.2%. Percentages of infants who ultimately received screening, diagnostic testing, and early intervention services - regardless of timing - were higher. During this period, LTF/D declined from 42.1% to 31.3% for diagnostic testing, and 39.4% to 20.3% for EI services. Diagnoses of hearing loss recorded increased from 0.9 to 1.7 per 1,000 infants screened, likely reflecting improved data.

Adjuvants can increase the magnitude and durability of the immune response generated by the vaccine antigen. Aluminum salts (Alum) remain the main adjuvant licensed for human use. A few new adjuvants have been licensed for use in human vaccines since the 1990s. QS-21, a mixture of saponin compounds, was included in the AS01-adjuvanted Shingrix vaccine. Here, we investigated the adjuvant effects of VSA-1, a newly developed semisynthetic analog of QS-21, on promoting protection in mice after vaccination with the inactivated split virus vaccine. The adjuvant effects of VSA-1 on improving vaccine efficacy after prime immunization were evident as shown by significantly higher levels of hemagglutination-inhibiting antibody titers and enhanced homologous protection compared to those by QS-21 and Alum adjuvants. The adjuvant effects of VSA-1 on enhancing heterosubtypic protection after two doses of adjuvanted vaccination were comparable to those of QS-21. T cell immunity played an important role in conferring cross-protection by VSA-1-adjuvanted vaccination. Overall, the findings in this study suggest that VSA-1 exhibits desirable adjuvant properties and a unique pattern of innate and adaptive immune responses, contributing to improved homologous and heterosubtypic protection by inactivated split influenza vaccination in mice.