Safety and immunogenicity of a recombinant hemagglutinin influenza–flagellin fusion vaccine (VAX125) in healthy young adults

Salivary IgA enhancement strategy for development of a nasal-spray anti-caries mucosal vaccine

“…The fusion strategy can be achieved by inserting vaccine target antigen at the N-terminus or C-terminus or within the hypervariable region of the flagellin. A number of vaccine candidates with this strategy have reached early stage clinical studies, and this represents one of the most promising new directions in vaccine development [13,14,[17][18][19].…”

“…The use of recombinant fusion flagellins containing PAc inserted into hypervariable region may be a simple and inexpensive way to enhance antigenicity of PAc for nasal immunization. The fact that recombinant flagellins have reached Phase I/II clinical trials should accelerate further studies in this direction [19,66].…”

“…Flagellin as the ligand of toll-like receptor 5 (TLR5) has been proven to be an effective mucosal adjuvant and become promising for clinical use [13][14][15][16][17][18][19]. We applied the recombinant flagellin as mucosal adjuvant in anti-caries vaccines by nasal immunization, either using flagellin directly by simple mixing with antigen or using fusion strategy to combine flagellin and the target antigen in a single fusion protein, proved the efficacy for enhancement of specific IgA response in oral fluids and better protection against caries [11,20,21].…”

New technologies for influenza vaccines

“…40 In young adults, doses of 0.5, 1 and 2 mg of a monovalent A/Solomon Islands/3/2006 (H1N1) HA-fusion protein candidate induced geometric mean hemagglutination inhibition (HI) titers against egg-grown virus of 587, 698 and 640 (1 mo after vaccination), and these remained elevated above 300 for 6 mo after vaccination. 45 A dose ranging study in older adults with a mean age of 72 y found that a single 5 or 8 mg dose of monovalent vaccine led to a HI geometric mean titer of 211-222 with 98% of those subjects achieving seroprotective titers and 75% seroconverting, indicating that a higher antigen content is needed for that age group. 44 The geometric mean antibody titers in this older age group were similar to or higher than those obtained with the licensed unadjuvanted high dose TIV.…”

Pesquisa de novos adjuvantes para vacinas terapêuticas.

“…Na forma monomérica o domínio D1 ainda apresenta estrutura em alfa-hélice, e esta conformação é indispensável para o reconhecimento pelo TLR5. Por outro lado, o domínio D0 apresenta-se sem estrutura, e seu reconhecimento por receptores NODlike se dá por meio da ligação aos últimos trinta e cinco resíduos de aminoácidos da região C-terminal (LIGHTFIELD et al, 2008 imunológica humoral e celular frente a diferentes antígenos (NEWTON et al, 1991a(NEWTON et al, , 1991bMIZEL et al, 2003;MURTHY et al, 2004 SONG et al, 2009;TREANOR et al, 2010;TURLEY et al, 2011 BEN-YEDIDIA et al, 1999a, 1999bJEON;ARNON, 2002;MIZEL et al, 2009;BARGIERI et al, , 2010 ou mesmo de outras bactérias (LEE et al, 2006) como adjuvante vacinal. Entretanto, existe grande controvérsia na literatura sobre a utilização de flagelinas híbridas, e enquanto alguns autores sugerem que a ligação física do antígeno não é um fator imprescindível para o efeito adjuvante da flagelina APPLEQUIST et al, 2005;LEE et al, 2006; outros apontam a necessidade de fusão como pré-requisito para sua adjuvanticidade BATES et al, 2011).…”