Immune prime-boost

The sera of mice fed with fresh spinach leaves infected with AlMV particles presenting a rabies virus epitope contained IgG and IgA. Mucosal IgA was also detected [48]. Human volunteers (in FDA approved trials) fed with spinach containing recombinant particles generated both IgG and IgA responses specific to the pathogen [49]. The trials also suggested that plant virus particle-based vaccines could be effectively used in prime-boost regimens. In more recent work, recombinant AlMV particles containing an epitope from the G protein of human respiratory syncytial virus (RSV) induced protective immunity in mice [33]. 

Active immunizations using DNA which codes for the protein against which the immune response will be directed (genetic immunizations) provide additional safety as the immune response in DNA immunizations differs from the response elicited by peptide immunizations [366]. Ap DNA epitope vaccines have been proposed with optimism possibly combined with a prime boost regime in either very early AD, or preferably in preclinical stage individuals identified by validated AD biomarkers [367],... 

The superior characteristics of MIDGE-ThI vectors for the purpose of immunization were affirmed by determination of amount of DNA necessary to induce antibodies against HBsAg, an antigen from hepatitis B virus, in a prime boost model (Fig. 7.8). The threshold for the induction of antibodies was 25 pg for plasmids, but less than 1 pg for MIDGE-ThI vectors. 

Fig. 7.12 Immunization of mice against Leishmania major. Specific vaccination was performed as depicted via prime/boost scheme using various vectors encoding LACK antigen before challenge with L major. Protection was measured using the size of footpath lesions.

Fig. 7.13 Cell-based vaccination against acute lymphoid leukemia in a murine model. Syngeneic mice were immunized via prime/boost scheme with BM185 tumorigenic cells that had been transfected with MIDGE vectors encoding CD80/B7.1 and GM-CSF either with addition of dSLIM (blue circles) or...

Lemckert A A, Sumida S M, Holterman L, et al. (2005). Immunogenicity of heterologous prime-boost regimens involving recombinant adenovirus serotype 11 (Adll) and Ad35 vaccine vectors in the presence of anti-ad5 immunity. J. Virol. 79 9694-9701. 

In order to develop an anti-prion vaccine, a novel DNA fusion vaccine composed of mouse PrP and immune stimulatory helper T-cell epitopes of the tetanus toxin has been developed (Nitschke et al., 2007). This approach provokes a strong PrP -specific humoral and cellular immune response in PrP null mice, but only low antibody titers are found in vaccinated wild-type mice. Furthermore, prime-boost immunization with the DNA vaccine and recombinant PrP protein increased antibody titres in PrP null mice, but failed to protect wild-type mice from mouse scrapie (Nitschke et al., 2007). 

McShane H, Brookes R, Gilbert SC, Hill AV. Enhanced immunogenicity of CD4(+) t-cell responses and protective efficacy of a DNA-modified vaccinia virus Ankara prime-boost vaccination regimen for murine tuberculosis. Infect Immun 2001 69(2) 681-686. 

E. coli 0157 H7 Intimin epitope Tobacco callus Mucosally immunogenic in mice when primed parenterally and boosted orally. Mice immunized parenterally and orally boosted showed reduced duration of colonization upon challenge. 92... 

In a more recent study, Webster et al. (2006) report the expression and characterization of lettuce-derived measles vaccine. The MV-H protein expressed in lettuce was demonstrated to be immunogenic in mice following intraperitoneal injection in the absence of adjuvant in addition to intranasal inoculation in the presence of a mucosal adjuvant. The highest response was observed in mice primed first with MV-H DNA and then boosted with an oral formulation of freeze-dried MV-H lettuce in conjunction with a mucosal adjuvant. In addition to this, the type of immune response was found to depend largely on the manner in which MV-H is presented to the immune system. Secreted and soluble forms of MV-H were demonstrated to induce a Th2 type response, while membrane-bound MV-H protein was found to be associated with a Thl response. 

Scheerlinck, J.P., Casey, G., McWaters, P., Kelly, J., Woollard, D., Lightowlers, M.W., Tennent, J.M. and Chaplin, P.J. (2001) The immune response to a DNA vaccine can be modulated by co-delivery of cytokine genes using a DNA prime-protein boost strategy. Vaccine 19, 4053-4060. 

Da Dara, A.A., Skelly, P.J., Walker, C.M. and Harn, D.A. (2003) A DNA-prime/protein-boost vaccination regimen enhances Th2 immune responses but not protection following Schistosoma mansoni infection. Parasite Immunology 25, 429 137. 

Rasmussen RA, Ong H, Kittel C, Ruprecht CR, Ferrantelh F, Hu SL, Polacino P, McKenna J, Moon J, Travis B, Ruprecht RM. DNA prime/protein boost immunization against HIV clade C safety and immunogenicity in mice. Vaccine 2006 24 2324-32. 

Crouch CE, Daly J, Henly W, Hannant D, Wilkins J, Erancis Ml (2005) The use of a systemic prime/mucosal boost strategy with an equine influenza ISCOM vaccine to induce protective immunity in horses. Vet Immunol Immunopathol 108 345-355. 

One evaluation of the results of two studies in a total of 182 children primed either with acellular or with wholecell pertussis vaccines at 2, 4, and 6 months of age and boosted with an acellular vaccine has shown that booster doses of acellular vaccine are safe and immunogenic (16). Local adverse reactions after booster immunization with acellular vaccine were more common in children primed with acellular vaccine than in those primed with wholecell pertussis vaccine (68 versus 33%). In another and similar study, children primed with acellular or whole cell pertussis combined with DT vaccine have been boosted with a recombinant acellular pertussis vaccine combined with DT vaccine. The vaccine was highly immunogenic and safe (17). 

Fig. 7.8 Specific antibody response after in-vivo HBsAg immunization. Mice received a prime and a boost injection (after 7 weeks) with either MIDGE, MIDGE-ThI vector or plasmid encoding HBsAg. At week 11, anti-HBsAg antibodies in the blood were determined using ELISA.

Sharpe S, Hanke T, Tinsley-Bown A, et al. (2003). Mucosal immunization with PLGA-microencapsulated DNA primes a SIV-specific CTL response revealed by boosting with cognate recombinant modified vaccinia virus Ankara. Virol. 313 13-21. Kusakabe K-I, Xin K-Q, Katoh H, et al. (2000). The timing of GM-CSF expression plasmid administration influences the Thl/Th2 response induced by an HI V-l-specific DNA vaccine. J. Immunol. 164 3102-3111. 

Castaldello, A., Brocca-Cofano, E., Voltan, R. et al. 2006. DNA prime and protein boost Immunization with innovative polymeric cationic core-sheU nanoparticles elicits broad immune responses and strongly enhance ceUrdar responses of HIV-1 tat DNA vaccination. Vaccine 24 5655-69. 

After three infusions of multiple-emulsions formulations, the animals produced both intestinal secratory IgA and circulating IgG antibody responses. The IgG titers persisted for one year and were boosted by a further oral immunization. Oral immunization using multiple emulsions also uniformly primed the animals for an increased response following parenteral immunization. 

Due to the limitations with the gastrointestinal tract, there are few studies available on chitosan-based delivery systems for oral vaccine delivery (Table 1). Van der Lubben et al. [66] were among the first to demonstrate that chitosan microparticles with a particle size smaller than 10 pm, incorporated with the model protein OVA as well as diphtheria toxoid (DT), were taken up by the Peyer s patch after intragastric administration to mice. A dose-dependent immune reaction was observed for mice vaccinated with different doses of DT associated to chitosan microparticles [67]. It was also observed that the immune response started only 1 week after the boosting, indicating the formation of memory cells after priming. 

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