A single immunization with inactivated H1N1 influenza vaccine formulated with delta inulin adjuvant (Advax™) overcomes pregnancy-associated immune suppression and enhances passive neonatal protection

Abstract

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 also potentially 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 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 not seen with administration of unadjuvanted vaccine, via enhanced breast milk transfer of anti-influenza antibodies.

Effect of sesamin against cytokine production from influenza type A H1N1-induced peripheral blood mononuclear cells: computational and experimental studies

“…The influenza virus type A H1N1, inactivated by β-propiolactone (Garlick et al 1976;Honda-Okubo et al 2014), was obtained from P r o f . Yo n g P o o v o r a w a n , F a c u l t y o f M e d i c i n e , Chulalongkorn University, Bangkok, Thailand.…”

Physical characterization and in silico modeling of inulin polymer conformation during vaccine adjuvant particle formation

“…This polysaccharide is biocompatible and biodegradable and specific semicrystalline particulate forms of inulin have immunomodulatory properties (Cooper & Petrovsky, 2011). The utility of γ- and δ-inulin isoforms as vaccine adjuvants has been demonstrated in both animal (Feinen, Petrovsky, Verma & Merkel, 2014; Honda-Okubo, Kolpe, Li & Petrovsky, 2014; Saade, Honda-Okubo, Trec & Petrovsky, 2013) and human (Gordon, Kelley, Heinzel, Cooper & Petrovsky, 2014; Gordon, Sajkov, Woodman & Honda-Okubo, 2012) studies. However, to fully realize the vaccine adjuvant benefit of inulin particles there is a need to better understand how inulin polymer chains assemble to form the adjuvant-active inulin particles.…”

Influenza immunization during pregnancy: Benefits for mother and infant

“…88 In animal models, Advax adjuvant markedly enhanced protection of maternally-immunized mothers but also their pups against an otherwise lethal influenza infection. 85 Importantly, Advax adjuvant had no adverse reproductive, teratogenic or developmental effects in immunized mothers or their pups. 85 Hence, along with other promising new influenza vaccine technologies currently in development, new adjuvants such as Advax could be used in the future to enhance influenza vaccine effectiveness in pregnant women and their infants.…”

“…Similarly, novel adjuvants have potential to enhance the effectiveness of both seasonal and pandemic influenza vaccines. 85,86 Again, it will first be important to establish the safety of such adjuvants in animal models of pregnancy to confirm absence of adverse reproductive, teratogenic or developmental effects. 85 One promising new adjuvant in this regard is a next-generation polysaccharide-based adjuvant developed from microcrystalline particles of delta inulin (Advax TM ).…”

“…85,86 Again, it will first be important to establish the safety of such adjuvants in animal models of pregnancy to confirm absence of adverse reproductive, teratogenic or developmental effects. 85 One promising new adjuvant in this regard is a next-generation polysaccharide-based adjuvant developed from microcrystalline particles of delta inulin (Advax TM ). Advax TM has been shown to improve the immunogenicity of seasonal and pandemic influenza vaccines in non-pregnant adult human subjects.…”