Effect of Adjuvants on Responses to Skin Immunization by Microneedles Coated with Influenza Subunit Vaccine

Abstract

Recent studies have demonstrated the effectiveness of vaccine delivery to the skin by vaccine-coated microneedles; however there is little information on the effects of adjuvants using this approach for vaccination. Here we investigate the use of TLR ligands as adjuvants with skin-based delivery of influenza subunit vaccine. BALB/c mice received 1 µg of monovalent H1N1 subunit vaccine alone or with 1 µg of imiquimod or poly(I:C) individually or in combination via coated microneedle patches inserted into the skin. Poly(I:C) adjuvanted subunit influenza vaccine induced similar antigen-specific immune responses compared to vaccine alone when delivered to the skin by microneedles. However, imiquimod-adjuvanted vaccine elicited higher levels of serum IgG2a antibodies and increased hemagglutination inhibition titers compared to vaccine alone, suggesting enhanced induction of functional antibodies. In addition, imiquimod-adjuvanted vaccine induced a robust IFN-γ cellular response. These responses correlated with improved protection compared to influenza subunit vaccine alone, as well as reduced viral replication and production of pro-inflammatory cytokines in the lungs. The finding that microneedle delivery of imiquimod with influenza subunit vaccine induces improved immune responses compared to vaccine alone supports the use of TLR7 ligands as adjuvants for skin-based influenza vaccines.

Hollow microneedle-mediated intradermal delivery of model vaccine antigen-loaded PLGA nanoparticles elicits protective T cell-mediated immunity to an intracellular bacterium

“…In agreement with this observation, multiple intradermal immunization studies using different administration methods have shown added effects of different Toll-like receptor (TLR) agonists based adjuvants [16,45]. In our study, co-delivery of OVA and the TLR3 agonist poly(I:C) in PLGA nanoparticles, led to protective cellular immune responses to rLM-OVA.…”

Toll-Like Receptor 7 Agonist Imiquimod in Combination with Influenza Vaccine Expedites and Augments Humoral Immune Responses against Influenza A(H1N1)pdm09 Virus Infection in BALB/c Mice

“…In our study, TLR7 appeared to play some role in the protection of the vaccine day Ϫ3 group because the removal of ssRNA from the vaccine day Ϫ3 group with RNase abolished the protective response of the vaccine day Ϫ3 group but not that of the VCI day Ϫ3 group. Weldon et al previously showed that imiquimod can enhance IFN-␥, leading to a Th1 cellular immune response and isotype switching, which resulted in a specific increase in the level of IgG2a (40). However, in our study, the increase in the pulmonary IFN-␥ level was much smaller in the VCI day Ϫ3 group than in the vaccine day Ϫ3 group, together with the increase in the total serum IgG, IgG2a, and IgG2b levels.…”

Suboptimal Humoral Immune Response against Influenza A(H7N9) Virus Is Related to Its Internal Genes

“…Body weight and percent survival were monitored daily for 14 days after virus inoculation. A body weight loss of 30% was set as the humane endpoint (8,17). At 7, 14, and 28 days postinfection (dpi), blood samples were taken, and serum samples were stored at Ϫ80°C in aliquots for subsequent testing.…”