Abstract
Probiotic microorganisms are currently considered as a promising platform for the development of recombinant vaccines expressing foreign antigens. In this study, we generated and evaluated the live mucosal recombinant vaccine by integrating genes encoding influenza virus neuraminidase (NA) of the N2 subtype into the DNA of the probiotic strain Enterococcus faecium L3 (L3). We confirmed NA expression in the pili of L3 using immune electron microscopy. Mice were fed with a probiotic vaccine containing the NA gene (L3-NA) or pure L3. Oral administration of L3-NA caused detectable increase in virus-specific serum IgG and local IgA after the third feeding. Immunization with L3-NA increased the survival rate by 34% when the mice were infected using A(H1N1)pdm09 influenza virus after the third feeding. After S. pneumoniae post-influenza infection, the L3-NA-immunized mice were 50% more protected from lethality in comparison with L3-fed mice. Thus, a live probiotic vaccine candidate based on L3 induced the formation of systemic and local immunity and provide partial protection against complicated influenza.
Highlights
IntroductionOne of the most promising approaches to the creation of mucosal vaccines is the use of probiotic vectors carrying viral components
The main advantage of live mucosal vaccines is the activations of all components of the immune system which induce a balanced, strong immune response
The putative insert of influenza neuraminidase of N2 subtype contained a number of B cell epitopes, including the epitope 222–230 described as common to influenza A viruses [31] (Figure 1a)
Summary
One of the most promising approaches to the creation of mucosal vaccines is the use of probiotic vectors carrying viral components. This approach promotes both the formation of humoral immunity, which has broad specificity for influenza virus strains, and the enhancement of the nonspecific activation of the immune system due to the immunomodulatory properties of the probiotic [2]. Like other live vaccines, these probiotic preparations promote the formation of the cellular component of adaptive immunity. The main advantage of live mucosal vaccines is the activations of all components of the immune system which induce a balanced, strong immune response. Oral administration of a probiotic vaccine may help to provide immunization among the population groups for whom vaccination is not allowed, as well as to practice frequent and repeated immunization, if necessary, such as against seasonal respiratory infections
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