Honda-Okubo Yoshikazu, Kolpe Annasaheb, Li Lei, Petrovsky Nikolai
Vaxine Pty Ltd, Bedford Park, Adelaide 5042, SA, Australia.
Vaxine Pty Ltd, Bedford Park, Adelaide 5042, SA, Australia; Department of Diabetes and Endocrinology, Flinders Medical Centre/Flinders University, Adelaide 5042, SA, Australia.
Vaccine. 2014 Aug 6;32(36):4651-9. doi: 10.1016/j.vaccine.2014.06.057. Epub 2014 Jun 21.
Pregnant women and neonates represent high-risk groups for influenza infection, and in general have suppressed responses to standard influenza vaccines due to pregnancy-associated immune suppression and immune system immaturity, respectively. We therefore wished to test whether addition of Advax™, a polysaccharide adjuvant based on delta inulin, to an inactivated influenza vaccine (A/H1N1/PR8) administered during pregnancy would safely enhance vaccine immunogenicity and thereby provide improved protection of pregnant mothers and their newborns. Pregnant mice received a single intramuscular injection of β-propiolactone-inactivated H1N1 antigen alone or with Advax adjuvant. Pregnant dams receiving Advax-adjuvanted vaccine exhibited significantly increased serum and breast milk anti-influenza IgG titers. This translated into higher serum anti-influenza IgG titers in the pups of these dams. Complete protection was seen in pups of dams that received Advax-adjuvanted vaccine whereas no survival was seen in pups of control mothers or mothers immunized with unadjuvanted influenza vaccine. Cross-fostering studies confirmed that enhanced protection of pups of dams that received Advax-adjuvanted vaccine was mediated by enhanced transfer of maternal IgG to the pups via breast-feeding. The delta inulin adjuvant was not associated with any reproductive or developmental adverse effects. This study shows that Advax adjuvant was safe when administered with influenza vaccine during pregnancy and provided protection of pups via enhanced breast milk transfer of anti-influenza antibodies, not seen with administration of unadjuvanted vaccine.
孕妇和新生儿是流感感染的高危人群，通常由于妊娠相关的免疫抑制和免疫系统不成熟，对标准流感疫苗的反应受到抑制。因此，我们希望测试在孕期接种的灭活流感疫苗（A/H1N1/PR8）中添加基于δ-菊粉的多糖佐剂Advax™是否能安全增强疫苗免疫原性，从而为孕妇及其新生儿提供更好的保护。怀孕小鼠单次肌肉注射单独的β-丙内酯灭活H1N1抗原或与Advax佐剂一起注射。接受Advax佐剂疫苗的怀孕母鼠血清和母乳中的抗流感IgG滴度显著增加。这导致这些母鼠的幼崽血清中抗流感IgG滴度更高。在接受Advax佐剂疫苗的母鼠的幼崽中观察到完全保护，而在对照母鼠或接种无佐剂流感疫苗的母鼠的幼崽中没有观察到存活情况。交叉寄养研究证实，接受Advax佐剂疫苗的母鼠对幼崽的增强保护是通过母乳喂养将母体IgG增强转移到幼崽中来介导的。δ-菊粉佐剂与任何生殖或发育不良反应均无关。这项研究表明，Advax佐剂在孕期与流感疫苗一起使用时是安全的，并通过增强母乳中抗流感抗体的转移为幼崽提供保护，而无佐剂疫苗则未观察到这种情况。
