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 primep arenteral 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. ß

Comparison of immune responses in parenteral FaeG DNA primed pigs boosted orally with F4 protein or reimmunized with the DNA vaccine

“…DNA boost, the oral F4 boost was clearly more immunogenic for the adjuvanted groups, as judged by an enhanced isotype switching towards IgG in the spleen and increased numbers of IgG ASC in the Cerv LN. This is in agreement with other studies demonstrating that prime-boost immunizations by alternating routes and/or immunization forms are as immunogenic or more immunogenic than homologous prime-boost immunizations (Baca-Estrada et al, 2000;McCluskie et al, 2002;Lauterslager et al, 2003). As observed previously (Melkebeek et al, 2007), boosting of systemic responses in parenterally primed pigs by oral F4 administration appeared to be independent of the F4R status of the pigs.…”

A Recombinant Hendra Virus G Glycoprotein Subunit Vaccine Protects Nonhuman Primates against Hendra Virus Challenge

“…Nevertheless, the present findings have clearly demonstrated that sG HeV -alum alone is also capable of providing complete protection from a HeV challenge. As HeV and NiV replicate and cause severe pathology in the lung and CpG motifs have been shown to elicit Th1 and mucosal immunity regardless of the immunization route used (34)(35)(36), the most recent sG vaccine studies have used and explored several CpG adjuvants. Additionally, several CpG motifs have also entered into human clinical trials, which could facilitate future regulatory processes for this adjuvant in general.…”

Possible Correlates of Long-Term Protection againstHelicobacter pylorifollowing Systemic or Combinations of Mucosal and Systemic Immunizations

“…Immunogenicity studies have also shown that the combination of mucosal priming followed by systemic boosting results in high antigenspecific antibody responses (25,39,40). However, in most H. pylori vaccine/protection studies immunized animals were challenged within a month after immunization, whereas we challenged the animals 3 months after immunization (11,13,15,20,24,34,35,43).…”

“…Unlike for Helicobacter felis, against which long-term protection can be achieved through immunization, a longterm-protection model for H. pylori has yet to be reported (27,33). Recent studies have demonstrated that immunization through a combination of mucosal and systemic routes may increase mucosal immunity (22,25,39,40).…”