Oral and intranasal Ad5 influenza vaccination induces hemagglutinin-specific and influenza neutralizing antibodies in serum and milk of pregnant and lactating ferrets

Abstract

Abstract Pregnant women and young children are at increased risk for severe influenza infection. While there are intramuscular (IM) inactivated influenza vaccines available to pregnant individuals, IM immunization may not be an ideal route to boost neutralizing antibodies in breastmilk (BM). Therefore, innovative vaccine strategies are needed to increase BM antibodies that promote neonatal protection against influenza. We hypothesize that maternal mucosal immunization stimulates a protective influenza-specific antibody response, by generating antibodies in both blood and BM. To test this, we immunized pregnant and lactating ferrets at two weeks prepartum and two weeks postpartum with an H1N1 hemagglutinin (HA) adenovirus type 5 (Ad5) vaccine via oral or intranasal routes. We detected HA-specific IgG antibodies in dam serum and HA-specific IgG and IgA antibodies in secreted milk after oral and intranasal immunization by ELISA and chemiluminescence assays. We demonstrated that serum and BM from oral and intranasally immunized dams neutralized influenza virus in vitro. Additionally, ferret kits born to oral and intanasally immunized dams had HA-specific IgG antibodies in circulation at 5–6 weeks of life. These preclinical data led to the announcement by Vaxart, Inc. that they will test their oral tablet vaccine in human lactating mothers to determine if vaccination induces BM antibodies. Future work includes using our ferret model to determine the relationship between BM antibody quantity and function and neonatal protection against influenza. An easy-to-deliver mucosal vaccine that boosts systemic and mucosal protective antibodies in the maternal-neonatal dyad is an ideal strategy for protection of these vulnerable populations. Bill and Melinda Gates Foundation grant INV-22595D