Immune Responses To Influenza Vaccine In Diabetic Kunming Mice And A Preliminary Study On The Mucosal Immunization With Influenza Vaccine

Influenza virus activity results in significant mortality, morbidity and economic disruption, particularly in those at high risk of developing complications, such as the elderly and diabetes mellitus. So far, the most effective method of protection against influenza is annual vaccination. There are some discrepancies between the results of studies carried out by different authors in diabetes. Some investigations indicated poorer humoral response to influenza vaccine in these patients, while others showed responses comparable to those in healthy individuals. In this study, diabetic mice were induced by injection of a single high dose of streptozotocin (STZ) in Kunming mice. We examined the antibody response to inactivated influenza vaccine and the protection against the influenza virus lethal challenge using Kunming mouse the diabetic model. Mice were immunized with inactivated influenza vaccine. After the immunization, mice were challenged with a lethal dose (40LD50) of influenza virus. The ability of protection against virus challenge in diabetic mice was evaluated by induction of serum antibody response, bodyweight loss and survival rate. The results demonstrate that diabetes could be protected against influenza virus with vaccination despite the metabolic loss control in diabetic mice.Until now, influenza vaccine needs to be injected due to low absorption at mucosal sites. Obvious disadvantages of parenteral drug delivery are the low patient compliance and high costs due to both high manufacturing costs of sterile products and the need for qualified personnel to administer the vaccine. The major factor, which impedes absorption at mucosal sites, is the low and incomplete transport across the epithelial barrier. Several groups have demonstrated that secretory immunoglobulin (IgA) confers protection against influenza virus in mice. Parenteral immunization with current influenza vaccines is generally efficient at eliciting serum antibody but not secretory IgA responses.An ideal influenza vaccine would induce both local respiratory and systemic immune responses. Generally, Secretary IgA forms the major part of the mucosal antibody response to influenza virus infection. A number of materialshave been investigated as adjuvant to improve antibodyresponses to antigens delivered mucosally, such as cholera toxin, Escherichia coli heat labile toxin, or derivatives thereof.In this study, we have investigated the adjuvant ability of the nontoxic carbohydrate biopolymers, chitosan, to increase the immunogenicity of administered influenza virus vaccines. The ability of chitosan to augment the immunogenicity of influenza vaccines was confirmed using an inactivated influenza virus. The experiments indicated that influenza vaccine plus chitosan is therefore an excellent candidate for an inactivated influenza vaccine.In order to study the oral DNA vaccines against the influenza virus, we used an attenuated strain of S. typhimurium as a vehicle for oral genetic immunization. Expression vectors containing influenza (A/PR/8/34) HA DNA gene was used to transform S. typhimurium. Oral immunization with such transformants induced antibody responses in tested mice.