Presenting Influenza A M2e Antigen on Recombinant Spores of Bacillus subtilis

• Published in: PloS one 2016-11, Vol.11 (11), p.e0167225
• Main Authors: Łęga, Tomasz, Weiher, Paulina, Obuchowski, Michał, Nidzworski, Dawid
• Format: Article
• Language: English
• Subjects: Adjuvants; Analysis; Animal models; Animals; Antibodies; Antigen Presentation; Antigens; Antigens, Viral - immunology; Bacillus; Bacillus subtilis; Bacillus subtilis - genetics; Biology and Life Sciences; Biotechnology; Care and treatment; Chromosomes - genetics; Cloning; Clostridium difficile; DNA, Recombinant - genetics; Dosage and administration; E coli; Escherichia coli; Experiments; Gene expression; Gene Fusion; Genetic aspects; Health aspects; Homology; Humans; Immune response; Immunization; Immunogenicity; Infections; Influenza; Influenza A; Influenza A virus - immunology; Laboratories; Livestock; Medical research; Medicine and Health Sciences; Mice; Mice, Inbred BALB C; Mucosa; Nucleotide sequence; Orthomyxoviridae; Pandemics; Peptides; Proteins; Research and Analysis Methods; Spore coats; Spores; Spores, Bacterial - genetics; Swine; Vaccination; Vaccines; Viral antibodies; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0167225

Effective vaccination against influenza virus infection is a serious problem mainly due to antigenic variability of the virus. Among many of investigated antigens, the extracellular domain of the M2 protein (M2e) features high homology in all strains of influenza A viruses and antibodies against M2e and is protective in animal models; this makes it a potential candidate for generation of a universal influenza vaccine. However, due to the low immunogenicity of the M2e, formulation of a vaccine based on this antigen requires some modification to induce effective immune responses. In this work we evaluated the possible use of Bacillus subtilis spores as a carrier of the Influenza A M2e antigen in mucosal vaccination. A tandem repeat of 4 consensus sequences coding for human-avian-swine-human M2e (M2eH-A-S-H) peptide was fused to spore coat proteins and stably exposed on the spore surface, as demonstrated by the immunostaining of intact, recombinant spores. Oral immunization of mice with recombinant endospores carrying M2eH-A-S-H elicited specific antibody production without the addition of adjuvants. Bacillus subtilis endospores can serve as influenza antigen carriers. Recombinant spores constructed in this work showed low immunogenicity although were able to induce antibody production. The System of influenza antigen administration presented in this work is attractive mainly due to the omitting time-consuming and cost-intensive immunogen production and purification. Therefore modification should be made to increase the immunogenicity of the presented system.