ABSTRACT
Each year, influenza A infections have caused tremendous death rate as high as 300,000-500,000 globally. Althoughthere are effective anti-influenza agents and vaccines, high mutational rate among influenza A viruses renders dramaticdecline in the effectiveness of anti-influenza agents or vaccines in certain individuals. The situation is further complicatedby limitations in influenza vaccine production, for instance, long production period, limited vaccine capacity and lackof cross-protection against various influenza A virus strains. To solve these issues, development of universal influenzavaccine based on conserved antigens such as non-stuctural protein 1 (NS1) has been endeavoured. NS1 protein is highlyconserved in all influenza A virus strains known by far, produced abundantly on infected cell surfaces and responsible formaintaining virulence. Furthermore, cytotoxic T-lymphocytes that are active against NS1 were also reported to be ableto avoid shedding of influenza in hosts. To better inhibit influenza infections, oral immunization has long been proposeddue to feasibility of this method to be implemented and safer for recipients while able to target influenza A viruses fromthe entry point. Lactobacillus has been vastly studied for its roles as bacterial carrier in oral vaccine development dueto its significant probiotic properties. For examples, stimulation of immune responses in oral and airway mucosal layers,high colonization in oral and airway mucosal layers and great natural adjuvant effects. In this light, influenza universaloral vaccine developed using NS1 dan Lactobacillus should be further studied in influenza oral vaccine design.
ABSTRACT
It was shown earlier that immune responses against cholera toxin (CT) as well as Vibrio cholerae lipopolysaccharide (LPS) or whole bacterial cells (WC) were protective and that these different antibody specificities co-operated synergistically for protection against experimental cholera. Similarly, antibodies against the heat-labile toxin (LT) and major colonization factors (CFs) of enterotoxingenic Escherichia coli (ETEC) co-operated synergistically for protection against LT-producing ETEC expressing homologous CFs. Studies in humans revealed that repeated oral antigen administration was optimal in inducing intestinal immune responses. Based on these findings oral inactivated vaccines consisting of toxin antigen and whole cells, i.e. the licensed recombinant cholera B subunit (rCTB)-WC cholera vaccine Dukoral®, and candidate ETEC vaccines have been developed. In different trials the rCTB-WC cholera vaccine has provided very high (85-100%) short term protection, which was significantly higher than that induced by the WC component alone, whereas rCTB-WC and WC alone provided comparable (50-60%), long term protection. An oral ETEC vaccine consisting of rCTB and formalin-inactivated E. coli bacteria expressing major CFs was shown to be safe and immunogenic in adults and children in different countries. The vaccine also induced significant protection against non-mild ETEC diarrhoea, i.e. diarrhoea interfering with daily activity in American travellers but not against ETEC diarrhoea in young children in Egypt. Against this background, a modified ETEC vaccine consisting of recombinant E. coli strains overexpressing the major CFs and a more LT like hybrid toxoid (LCTBA) has been developed. This vaccine will be tested soon alone and together with a mucosal adjuvant, i.e. dmLT, in clinical trials.