Parenteral and mucosal prime-boost immunization strategies in mice with hepatitis B surface antigen and CpG DNA

Abstract

Synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs (CpG ODN) are potent adjuvants to protein antigens administered by parenteral or mucosal routes to BALB/c mice. To date, there have been no studies using combined parenteral/mucosal approaches with CpG DNA as adjuvant. In this study we evaluated different parenteral prime-mucosal boost and mucosal prime-parenteral boost strategies using hepatitis B surface antigen (HBsAg) alone or with different adjuvants: aluminum hydroxide (alum), cholera toxin (CT), CpG ODN. In addition, since CpG ODN has previously been shown to act synergistically with other adjuvants after parenteral or mucosal delivery, we also evaluated adjuvant combinations: alum+CpG ODN and CT+CpG ODN. The effects of adjuvant and administration strategy on systemic and mucosal humoral responses were measured, as well as cell-mediated immune responses (cytotoxic T lymphocyte activity). These results were compared to parenteral only or mucosal only strategies. Our findings demonstrate that parenteral immunization can prime for mucosal responses even when different lymph nodes were being targeted. HBsAg-specific immune responses (IgG in plasma, cytotoxic T lymphocytes) induced by parenteral prime could all be significantly enhanced by mucosal boosting and despite the fact that intramuscular immunization alone could not induce mucosal IgA, it could prime for a subsequent mucosal boost. In addition, the presence of adjuvant at time of boosting could influence the nature of subsequent immune responses (Th1 vs. Th2). Mice primed intranasally could have their systemic immune responses boosted with a parenteral administration and it was also possible to enhance mucosal responses induced by intranasal prime with an intramuscular boost.

Alginate coated chitosan nanoparticles are an effective subcutaneous adjuvant for hepatitis B surface antigen

“…Moreover, this paper investigates the co-administration of CpG ODN 1826, a potent adjuvant in mice that was shown to induce Th1 type immune response in combination with a number of different antigens, such as influenza virus [14], hepatitis B antigen [15][16][17], and tetanus toxoid [18], with the nanoparticles.…”

Oligodeoxynucleotides containing synthetic immunostimulatory motifs augment potent Th1 immune responses to HBsAg in mice

“…A number of previous studies have shown the adjuvant activity of CpG DNAs (TLR9 modulators similar to 1 or 3 used in the present study) with HBsAg in mouse models [25][26][27][28][29][30][31][32][33]. CpG DNA has also been used as an adjuvant with HBsAg in early clinical trials [34].…”

“…Because of their ability to induce strong Th1 immune responses, CpG DNA compounds have been studied as adjuvants to several vaccines and antigens, including recombinant HBsAg, in preclinical and early clinical studies [25][26][27][28][29][30][31][32][33][34]. In the present study, we investigated the adjuvant activity of CpR-, or R'pG-containing IMOs in a HBsAg immunization model compared with a conventional CpG DNA.…”

Progress Towards a Needle-Free Hepatitis B Vaccine

“…CpG ODN has been shown to be an effective mucosal adjuvant after the administration to different mucosal surfaces such as respiratory tract (73,181,182), the genitourinary tract (183) and the gastrointestinal tract (184,185) in combination with different antigens including the hepatitis B antigen (73,186). Co-administration of CpG ODN with other immunopotentiators or delivery systems has been considered to be useful, especially because of being a strong Th1 profile inducer, which has been shown to be able to dominate the Th2 bias associated with other adjuvants (72,73).…”