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The most widely used influenza vaccines are prepared by chemical inactivation. However, chemical, especially formalin, treatment-induced modifications of the antigenic structure of the virus are frequently associated with adverse effects including low efficacy of protection, unexpected immune responses, or exacerbation of disease. Gamma-irradiation was suggested as an alternative influenza virus inactivation method due to its great features of completely inactivating virus while not damaging the structures of protein antigens, and cross-protective ability against heterologous strains. However, immunological features of gamma radiation-inactivated influenza vaccine have not been fully understood. In this study, we aimed to investigate the humoral and cellular immune responses of gamma radiation-inactivated influenza vaccine. The gamma irradiation-inactivated influenza vaccine (RADVAXFluA) showed complete viral inactivation but retained normal viral structure with functional activities of viral protein antigens. Intranasal immunization of RADVAXFluA provided better protection against influenza virus infection than formalin-inactivated influenza virus (FIV) in mice. RADVAXFluA greatly enhanced the production of virus-specific serum IgG and alveolar mucosal IgA, which effectively neutralized HA (hemagglutinin) and NA (neuraminidase) activities, and blocked viral binding to the cells, respectively. Further analysis of IgG subclasses showed RADVAXFluA-immunized sera had higher levels of IgG1 and IgG2a than those of FIV-immunized sera. In addition, analysis of cellular immunity found RADVAXFluA induced strong dendritic cells (DC) activation resulting in higher DC-mediated activation of CD8+ T cells than FIV. The results support improved immunogenicity by RADVAXFluA.

Streptococcus agalactiae (group B Streptococcus, GBS) is a leading cause of severe invasive disease in neonate, elderly, and immunocompromised patients worldwide. Despite recent advances in the diagnosis and intrapartum antibiotic prophylaxis (IAP) of GBS infections, it remains one of the most common causes of neonatal morbidity and mortality, causing serious infections. Furthermore, recent studies reported an increasing number of GBS infections in pregnant women and elderly. Although IAP is effective, it has several limitations, including increasing antimicrobial resistance and late GBS infection after negative antenatal screening. Maternal immunization is the most promising and effective countermeasure against GBS infection in neonates. However, no vaccine is available to date, but two types of vaccines, protein subunit and capsular polysaccharide conjugate vaccines, were investigated in clinical trials. Here, we provide an overview of the GBS vaccine development status and recent advances in the development of immunoassays to evaluate the GBS vaccine clinical efficacy.

Group B Streptococcus (GBS) is a leading cause of sepsis in infants as well as chorioamnionitis in pregnant women. Opsonophagocytic killing assays (OPAs) are an essential technique in vaccine studies of encapsulated bacteria for estimating serotype-specific functional antibody levels in vitro. Here, we developed a three-fold multiplexed OPA (MOPA) to enable practical, large-scale assessment of GBS vaccine immunogenicity, including against serotypes Ia, III, and V. First, three target bacteria strains resistant to streptomycin, spectinomycin, or kanamycin were generated by natural selection through exposure to increasing antibiotic concentrations. Since a high level of nonspecific killing (NSK) of serotype V was observed in a 12.5% baby rabbit complement (BRC) solution, the BRC concentration was optimized. The final GBS-MOPA BRC concentration was 9%, which resulted in less than 20% NSK. The specificity was measured by preabsorbing serum with inactivated GBS. The opsonic index (OI) of preabsorbed serum with the homologous serotype GBS was significantly reduced in all three serotypes tested. The accuracy of the MOPA was compared with that of a single OPA (SOPA) with 35 serum samples. The OIs of the MOPA correlated well with those of the SOPA, and the r2 values were higher than 0.950 for all three serotypes. The precision of the MOPA assay was assessed in five independent experiments with five serum samples. The inter-assay precision of the GBS-MOPA was 12.5% of the average coefficient of variation. This is the first report to develop and standardize a GBS-MOPA, which will be useful for GBS vaccine development and evaluation.