Abstract
BackgroundMany pathogens initiate infection at the mucosal surfaces; therefore, induction of mucosal immune responses is a first level of defense against infection and is the most powerful means of protection. Although intramuscular injection is widely used for vaccination and is effective at inducing circulating antibodies, it is less effective at inducing mucosal antibodies.Methodology/Principal FindingsHere we report a novel recombinant, attenuated Sendai virus vector (GP42-H1) in which the hemagglutinin (HA) gene of influenza A virus was introduced into the Sendai virus genome as an additional gene. Infection of CV-1 cells by GP42-H1 resulted in cell surface expression of the HA protein. Intranasal immunization of mice with 1,000 plaque forming units (pfu) of GP42-H1 induced HA-specific IgG and IgA antibodies in the blood, brochoalveolar lavage fluid, fecal pellet extracts and saliva. The HA-specific antibody titer induced by GP42-H1 closely resembles the titer induced by sublethal infection by live influenza virus; however, in contrast to infection by influenza virus, immunization with GP42-H1 did not result in disease symptoms or the loss of body weight. In mice that were immunized with GP42-H1 and then challenged with 5LD50 (1250 pfu) of influenza virus, no significant weight loss was observed and other visual signs of morbidity were not detected.ConclusionsThese results demonstrate that the GP42-H1 Sendai virus recombinant is able to confer full protection from lethal infection by influenza virus, supporting the conclusion that it is a safe and effective mucosal vaccine vector.
Highlights
Induction of immune responses at sites where pathogens initiate replication is crucial for the prevention of infection
These results demonstrate that the GP42-H1 Sendai virus recombinant is able to confer full protection from lethal infection by influenza virus, supporting the conclusion that it is a safe and effective mucosal vaccine vector
Using the GP42-SeV mutant that was previously described [6], the GP42-green fluorescent protein (GFP) vector was generated [19] and the HA gene of influenza Puerto Rico/8/ 1934 (PR/8) virus was introduced in the intergenic sequence of the viral genome between the M and the F genes to generate the GP42-H1 vector (Fig. 1A)
Summary
Induction of immune responses at sites where pathogens initiate replication is crucial for the prevention of infection. IgA is the predominant antibody class produced in the upper respiratory tract, passive transport of IgG antibody from the systemic circulation onto the mucosal surfaces can enhance protection from virus infection in these tissues [4]. Together, these studies highlight the collaborative roles of IgA and IgG in the mucosal surfaces in the protection from influenza virus infections [3,4]. Intramuscular injection is widely used for vaccination and is effective at inducing circulating antibodies, it is less effective at inducing mucosal antibodies
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