Development of mucosal adjuvants for intranasal vaccine for H5N1 influenza viruses

Abstract

An increasing number of infections of highly pathogenic avian influenza virus (H5N1) in humans has been reported in South-East Asia and other areas of the world. High mortality (>60%) of this viral infection and its pathosis of systemic infection are features of this new human disease. Moreover, there is great concern that this avian H5N1 virus could cause a pandemic of new influenza in humans, once it acquires the ability for human to human transmission. To prevent such highly contagious infectious diseases as influenza, it is essential to prepare effective vaccines. Especially in the case of new influenza virus, we cannot predict the strain which will cause the pandemic. In such a situation, a vaccine that induces cross-protective immunity against variant viruses is extremely important. However currently used parenteral seasonal influenza vaccine is strain-specific, and is less effective against variant viruses. In order to overcome the weakness of current vaccines we need to learn from the immune responses induced by natural infection with influenza viruses. In the case of mucosally acquired acute respiratory infection such as influenza, mucosal immunity induced by natural infection plays important role in protection against the infection, as mucosal secretory IgA antibody plays an important role in cross-protection. In this review we describe the advantages and development of mucosal vaccine against highly pathogenic H5N1 influenza viruses.

Figure 1

Defence mechanism at mucosal site, innate and adaptive immunity.

Figure 2

H5N1 virus titers in nasal washes and survival rates after lethal challenge with homologous A/Vietnam, heterologous A/Hong Kong, or heterologous A/Indonesia viruses. Mice were immunized intranasally (solid bar) or subcutaneously (gray bar) with vaccine and Ampligen^®, then challenged by intranasal administration of 1000 PFU of A/Vietnam (A), A/Hong Kong (B), or A/Indonesia (C) virus 14 days after the final immunization. Nasal washes were collected three days post infection (d.p.i), and virus titers were measured by plaque assay. Each bar represents the mean ± SD of five mice and open circles indicate individual animals. For statistical analysis, virus titers were compared to those from control mice (open bar) that received intranasal administration of 10 μg of Ampligen^® alone. Survival rates were monitored for 18 days. Copyright © 2007. Reproduced with permission from Ichinohe T, Kawaguchi A, Tamura S, et al. Intranasal immunization with H5N1 vaccine plus Poly I:Poly C12U, a Toll-like receptor agonist, protects mice against homologous and heterologous virus challenge. Microbes Infect. 2007; 9:1333–1340. Note: *p < 0.05.