Brian R Sloat1, Zhengrong Cui. 1. Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon 97331, USA.
Abstract
PURPOSE: The current anthrax vaccine adsorbed (AVA) was originally licensed for the prevention of cutaneous anthrax infection. It has many drawbacks, including the requirement for multiple injections and subsequent annual boosters. Thus, an easily administrable and efficacious anthrax vaccine is needed to prevent the most lethal form of anthrax infection, inhalation anthrax. We propose to develop a nasal anthrax vaccine using anthrax protective antigen (PA) protein as the antigen and synthetic double-stranded RNA in the form of polyriboinosinic-polyribocytidylic acid (pI:C) as an adjuvant. METHODS: Mice were nasally immunized with recombinant PA admixed with pI:C. The resulting PA-specific antibody responses and the lethal toxin neutralization activity were measured. Moreover, the effect of pI:C on dendritic cells (DCs) was evaluated both in vivo and in vitro. RESULTS: Mice nasally immunized with rPA adjuvanted with pI:C developed strong systemic and mucosal anti-PA responses with lethal toxin neutralization activity. These immune responses compared favorably to that induced by nasal immunization with rPA adjuvanted with cholera toxin. Poly(I:C) enhanced the proportion of DCs in local draining lymph nodes and stimulated DC maturation. CONCLUSIONS: This pI:C-adjuvanted rPA vaccine has the potential to be developed into an efficacious nasal anthrax vaccine.
PURPOSE: The current anthrax vaccine adsorbed (AVA) was originally licensed for the prevention of cutaneous anthraxinfection. It has many drawbacks, including the requirement for multiple injections and subsequent annual boosters. Thus, an easily administrable and efficacious anthrax vaccine is needed to prevent the most lethal form of anthraxinfection, inhalation anthrax. We propose to develop a nasal anthrax vaccine using anthrax protective antigen (PA) protein as the antigen and synthetic double-stranded RNA in the form of polyriboinosinic-polyribocytidylic acid (pI:C) as an adjuvant. METHODS:Mice were nasally immunized with recombinant PA admixed with pI:C. The resulting PA-specific antibody responses and the lethal toxin neutralization activity were measured. Moreover, the effect of pI:C on dendritic cells (DCs) was evaluated both in vivo and in vitro. RESULTS:Mice nasally immunized with rPA adjuvanted with pI:C developed strong systemic and mucosal anti-PA responses with lethal toxin neutralization activity. These immune responses compared favorably to that induced by nasal immunization with rPA adjuvanted with cholera toxin. Poly(I:C) enhanced the proportion of DCs in local draining lymph nodes and stimulated DC maturation. CONCLUSIONS: This pI:C-adjuvanted rPA vaccine has the potential to be developed into an efficacious nasal anthrax vaccine.
Authors: Paolo Ascenzi; Paolo Visca; Giuseppe Ippolito; Andrea Spallarossa; Martino Bolognesi; Cesare Montecucco Journal: FEBS Lett Date: 2002-11-20 Impact factor: 4.124
Authors: Kerstin N Schmidt; Beatrice Leung; Mandy Kwong; Kol A Zarember; Sanjeev Satyal; Tony A Navas; Fay Wang; Paul J Godowski Journal: J Immunol Date: 2004-01-01 Impact factor: 5.422
Authors: B E Ivins; M L Pitt; P F Fellows; J W Farchaus; G E Benner; D M Waag; S F Little; G W Anderson; P H Gibbs; A M Friedlander Journal: Vaccine Date: 1998-07 Impact factor: 3.641
Authors: D R Strayer; W A Carter; I Brodsky; P Cheney; D Peterson; P Salvato; C Thompson; M Loveless; D E Shapiro; W Elsasser Journal: Clin Infect Dis Date: 1994-01 Impact factor: 9.079
Authors: Y L Yang; L F Reis; J Pavlovic; A Aguzzi; R Schäfer; A Kumar; B R Williams; M Aguet; C Weissmann Journal: EMBO J Date: 1995-12-15 Impact factor: 11.598
Authors: Aaron T Phillips; Tony Schountz; Ann M Toth; Amber B Rico; Donald L Jarvis; Ann M Powers; Ken E Olson Journal: J Virol Date: 2013-11-20 Impact factor: 5.103
Authors: S D Klas; C R Petrie; S J Warwood; M S Williams; C L Olds; J P Stenz; A M Cheff; M Hinchcliffe; C Richardson; S Wimer Journal: Vaccine Date: 2008-08-12 Impact factor: 3.641
Authors: Amit Kumar; Piyanuch Wonganan; Michael A Sandoval; Xinran Li; Saijie Zhu; Zhengrong Cui Journal: J Control Release Date: 2012-08-19 Impact factor: 9.776
Authors: Robert J Cybulski; Patrick Sanz; Dennis McDaniel; Steve Darnell; Robert L Bull; Alison D O'Brien Journal: Vaccine Date: 2008-07-25 Impact factor: 3.641