PubMed · 10704331
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F Rodriguez, J L Whitton. 2000-03-15. Enhancing DNA immunization.. https://doi.org/10.1006/viro.2000.0209
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The use of biodegradable polymer matrices as a single-dose vaccine delivery system was investigated using tetanus toxoid (TT) and diphtheria toxoid (DT). BALB/c mice were immunized with TT or DT in different formulations including individual, in minipellet and aluminum hydroxide (alum), and the antibody responses were monitored for 48 weeks. Antigens entrapped in minipellet elicited higher antibody responses compared to those obtained with individual antigens and antigens adsorbed to alum and the antibody levels remained elevated over 48 weeks. In addition, minipellet formulations induced the same subclasses of antibodies induced by alum formulations. These results raise the possibility to obtain optimal and long-lasting immune responses by a single administration of minipellet formulations.
Synthetic oligodeoxynucleotides containing CpG immunostimulatory sequences (ISS) have been shown to act as potent adjuvants of type 1 immune responses when co-administered with protein or peptide vaccines. We have recently shown that ISS can increase the anti-polysaccharide (CHO) and anti-tetanus toxoid (TT) or anti-diphtheria (CRM) toxoid antibody levels if used as adjuvant of anti-Haemophilus influenzae type b (Hib) CHO vaccine conjugated with TT or CRM. The analysis of anti-TT and anti-CRM IgG subclasses showed a significant increase in IgG2a, IgG2b and/or IgG3 in the presence of ISS. Anti-TT and anti-CRM antibodies were shown to neutralize the activity of both the tetanus and diphtheria toxin in vivo or in vitro tests respectively. These data show that ISS have the potential to increase host antibody response against both the CHO and the protein component of a conjugated vaccine, and encourage the investigation to identify strategies of vaccination with schedules aimed at the valuation of protein carriers as protective immunogens.
To identify specific receptors for immunostimulatory sequence (ISS), a cDNA library of human bone marrow was screened by one-hybrid system using ISS as bait. Among four duel-positive clones isolated so far, two encode light chain of immunoglobulin (Ig) homologous to anti-DNA and anti-HBsAg (HBsAb), respectively, suggesting a direct interaction between ISS and Igs. ELISA revealed that HBsAb, as well as Igs in normal mouse serum and a monoclonal anti-v5 antibody, bound to plasmid DNA in a pH-dependent way; more importantly, the plasmids inserted with more copies of ISS shown higher reactivity with these Igs than their blank vectors. Electrophoretic mobility shift assay (EMSA) showed HBsAb bound to oligonucleotides (ODN) also in a pH-dependent and ISS-specific way. Furthermore, ISS-containing ODN could enhance the binding of Igs to plasmid DNA at acidic pH. These results support existence of direct ISS-Ig interaction and demonstrated that DNA-Ig interaction could be up-modulated by ISS. In consideration of the crucial role of membrane Ig (mIg) in B cell activation, these results suggest mIg may be a candidate ISS receptor in ISS-induced B cell activation.