The slow-release platform, VacSIM, shapes host immune response against influenza infection after vaccination.

Abstract Influenza virus is a leading cause of respiratory infections known to cause global morbidity and mortality, despite the widespread use of multiple influenza vaccines. Current influenza vaccines target the hemagglutinin (HA) envelope protein responsible for the attachment and entry of influenza into host cells. However, high mutation rates during influenza replication lead to mutations that cause the HA protein to be unrecognizable by host antibodies, increasing levels of infection within both vaccinated and unvaccinated individuals. A promising approach to circumvent this problem is through the use of a slow release delivery platform which has been previously shown to induce the longevity of germinal center reactions, allowing for the generation of higher affinity antibodies and more evolved B cells. Here we show that vaccination with the slow-delivery platform, Vaccine Self-Assembling Immune Matrix (VacSIM), in combination with recombinant HA antigens, increases antibody titers against H1 and H3 HAs in vaccinated groups of mice. When mice immunized with VacSIM/H1 HA were challenged with a lethal H1N1 dose, a 25% increase in survival was seen compared to the non-VacSIM group and 100% increase against mock immunized. Similarly, when immunized with VacSIM/H3 HA and challenged with H3N2, a 1.8 log reduction in lung viral titers was seen. Further analysis of the vaccine-elicited antibodies showed that vaccination with VacSIM and HA increases HAI activity against multiple strains of influenza within both H1N1 and H3N2 subtypes. We anticipate that use of VacSIM will provide further insight into how consistent exposure through a slow delivery platform can shape the host immune response to increase protection against influenza infection. Supported by grants from CIVIC