Poly(I:C)/Alum Mixed Adjuvant Priming Enhances HBV Subunit Vaccine-Induced Immunity in Mice When Combined with Recombinant Adenoviral-Based HBV Vaccine Boosting

Abstract

BackgroundVirus-specific cellular immune responses play a critical role in virus clearance during acute or chronic HBV infection. Currently, the commercially available HBV vaccine is combined with alum adjuvant, which stimulates mainly Th2 immune responses. Therefore, development of new therapeutic HBV vaccine adjuvants and immune strategies that also promote Th1 and CTL responses is urgently needed.Methodology/Principal findingsTo improve the immunity induced by the novel HBSS1 HBV vaccine, we evaluated the ability of adjuvants, including alum, CpG and polyriboinosinic polyribocytidylic acid [poly(I:C)], to enhance the response when boosted with the recombinant adenoviral vector vaccine rAdSS1. The immune responses to different adjuvant combinations were assessed in C57BL/6 mice by enzyme-linked immunosorbent assay (ELISA), ELISpot and cytokine release assays. Among the combinations tested, a HBV protein particle vaccine with CpG/alum and poly(I:C)/alum priming combinations accelerated specific seroconversion and produced high antibody (anti-PreS1, anti-S antibody) titres with a Th1 bias. After boosting with recombinant adenoviral vector vaccine rAdSS1, both groups produced a strong multi-antigen (S and PreS1)-specific cellular immune response. HBSS1 immunisation with poly(I:C)/alum priming also generated high-level CD4+ and CD8+ T cell responses in terms of Th1 cytokines (IFN-γand IL-2).ConclusionsThe protein-vaccine HBSS1 with mixed poly(I:C)/alum adjuvant priming, followed by a rAdSS1 vaccine boost, maximises specific antibody and Th1-biased cellular immune responses. This regime might prove useful in the development of HBV therapeutic vaccines. Furthermore, this promising strategy might be applied to vaccines against other persistent infections, such as human immunodeficiency virus and tuberculosis.

Adsorption of a synthetic TLR7/8 ligand to aluminum oxyhydroxide for enhanced vaccine adjuvant activity: A formulation approach

“…Moreover, adsorption to aluminum of TLR ligands co-localizes antigen and adjuvant, and facilitates reduction of antigen and/or TLR ligand dose [5], [6], [7]. Therefore it is of high interest to develop aluminum salt-based formulations of other pattern recognition receptor (PRR) ligands (besides TLR4 agonists) to enhance antigen-specific Th1-type immunogenicity and protective efficacy [5], [8], [9]. Some PRR ligands, such as the TLR4 ligand MPL® and the TLR9 ligand CpG oligonucleotides, adsorb to some aluminum salts due to physicochemical structure compatibility.…”

Protective efficacy and hepatitis B virus clearance in mice enhanced by cell‐mediated immunity with novel prime‐boost regimens

“…Both HBSS1 (B genotype; subtype adr) and rAdSS1 vaccines containing S and preS1 fusion gene fragments were prepared as described previously . Aluminium hydroxide (alum) and poly(I:C) were used as adjuvants in this study and were formulated with the HBSS1 vaccine prior to immunization as described in previous reports …”

“…Compared with the current “S region only” vaccines, a vaccine regimen with PreS1 inclusion may enhance protective immunity and reduce the risk of selection for escape mutations . Furthermore, preS1‐specific antibodies were produced earlier than S‐specific antibodies; preS1‐specific cell‐mediated immune responses may help confer HBV protection in nonresponders . Our previous data suggested that the vaccine protein HBSS1, expressed in CHO cells containing S (1‐223 aa) and preS1 (21‐47 aa) combined with DNA or a viral vector‐based vaccine, could elicit specific anti‐HBV humoral and cell‐mediated immunity (CMI) in mice .…”

Sweeten PAMPs: role of sugar complexed PAMPs in innate immunity and vaccine biology

“…Co-administration of poly- L -Lysine and carboxymethylcellulose along with poly(I:C) and with Plasmodium falciparum circumsporozoite protein (CSP) antigen increase the frequency of activation of CD8 + Th1 cells and anti-CSP-Abs production (184). Furthermore, immunization of mice with CpG-ODNs or poly(I:C) and alum adjuvant with HBV vaccine rAdSS1 [adenoviral vector encoding HBV S (1–223aa) and pre S (1–47aa) fusion gene] shows immune protection through CD4 + T cells and CD8 + T cells via IFN-γ and IL-12 production and inducing cytotoxic effects, suggesting their potential application in vaccine biology for protection from HBV (185, 186). Since it is known that poly(I:C) and CpG-ODNs are potent immune adjuvant, their use in combination has been shown as potential immune adjuvant functions.…”