"Pathogen-mimicking" nanoparticles for vaccine delivery to dendritic cells

A clinically relevant delivery system that can efficiently target and deliver antigens and adjuvant to dendritic cells (DCs) is under active investigation. Immunization with antigens and immunomodulators encapsulated in poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles elicits potent cellular immune responses; but understanding how this mode of delivery affects DCs and priming of naive T cells needs further investigation. In the current study, we assessed the extent of maturation of DCs after treatment with monophosphoryl lipid A (MPLA) encapsulated in PLGA nanoparticles and the generation of primary T-cell immune responses elicited by DCs loaded with antigens using this approach. Results indicated that DCs up-regulated the expression of surface maturation markers and demonstrated an enhanced allostimulatory capacity after treatment with MPLA containing PLGA nanoparticles. Treatment of DCs with MPLA containing nanoparticles released high amounts of proinflammatory and TH1 (T helper 1) polarizing cytokines and chemokines greater than that achieved by MPLA in solution. The delivery of ovalbumin in PLGA nanoparticles to DCs induced potent in vitro and in vivo antigen-specific primary TH1 immune responses that were furthermore enhanced with codelivery of MPLA along with the antigen in the nanoparticle formulation. Delivery of MUC1 lipopeptide (BLP25, a cancer vaccine candidate) and MPLA in PLGA nanoparticles to human DCs induced proliferation of MUC1 reactive T cells in vitro demonstrating the break in tolerance to self-antigen MUC1. These results demonstrated that targeting antigens along with toll-like receptor ligands in PLGA nanoparticles to DCs is a promising approach for generating potent TH1 polarizing immune responses that can potentially override self-tolerance mechanisms and become beneficial in the immunotherapy of cancer and infectious diseases.     

Functional Aspects of Intrahepatic Hepatitis B Virus-specific T Cells Induced by Therapeutic DNA Vaccination

Current therapies for the hepatitis B virus (HBV), a major cause of severe liver disease, suppress viral replication but replication rebounds if therapy is withdrawn. It is widely accepted that immune activation is needed to control replication off-therapy. To specifically activate T cells crossreactive between the hepatitis B core and e antigens (HBcAg/HBeAg) in chronically infected patients, we developed a therapeutic vaccine candidate. The vaccine encompass codon-optimized HBcAg and IL-12 expressing plasmids delivered using targeted high-pressure injection combined with in vivo electroporation. One dose of the vaccine primed a B-cell-independent polyfunctional T-cell response, in wild-type, and in HBeAg-transgenic mice with an impaired ability to respond to HBc/eAg. The response peaked at 2 weeks and contracted at week 6 after vaccination. Coadministration of IL-12 improved antibody levels, and T-cell expansion and functionality. The vaccine primed T cells that, 2 weeks after a single dose, cleared hepatocytes transiently expressing HBcAg in vaccinated wild-type and HBeAg-transgenic mice. However, 4 weeks later, these functional responses were lost. Booster doses after 8–12 weeks effectively restored function and expansion of the rapidly contracting T cells. Thus, this vaccine strategy primes functional HBcAg-specific T cells in a host with dysfunctional response to HBV.     

DNA vaccines.

Chronic infections with hepatitis B (HBV) and hepatitis C (HCV) virus are worldwide problems often leading to the development of chronic liver disease and hepatocellular carcinoma. Genetic immunizations with DNA encoding for structural and nonstructural proteins of HCV and HBV in experimental mice generate a broad base CD4+ and CD8+ cellular immune response which may be required for viral clearance from the host. DNA based immunization is a promising antiviral approach for the development of therapeutic and prophylactic vaccine against HBV and HCV.     

Efficacy of recombinant adenovirus as vector for allergen gene therapy in a mouse model of type I allergy

DNA-based immunization represents an attractive alternative approach to the current treatment of allergic diseases by specific immunotherapy with allergen extracts. In this study, we used a replication-deficient adenovirus vector (AdCMV), to examine the in vivo efficacy of preventive and therapeutic genetic immunization in a mouse model of type I allergy. Primary immunization with a recombinant adenovirus expressing the model antigen beta-galactosidase (AdCMV-(beta)gal) induced a Th1 immune response (predominance of IgG2a antibodies, high frequency of IFN-gamma producing T cells) and large numbers of cytotoxic T lymphocytes. Prophylactic vaccination with AdCMV-(beta)gal abolished the production of specific IgE following subsequent immunization with (beta)gal-protein, and skewed the Th2-biased immune response to a Th1-orientated response. In contrast, therapeutic administration of AdCMV-(beta)gal after priming with (beta)gal-protein neither significantly inhibited ongoing IgE production nor modulated a manifest Th2 immune response. Thus, allergen gene transfer via recombinant adenovirus represents an effective method to establish protection against the development of allergic disorders, but does not qualify as a therapeutic tool to interfere with ongoing high IgE production.     

Induction of ErbB-2/neu-specific protective and therapeutic antitumor immunity using genetically modified dendritic cells: enhanced efficacy by cotransduction of gene encoding IL-12

Overexpression of ErbB-2/neu occurs in 20-30% of patients with breast cancer and indicates a poor prognosis. The presence of a detectable immune response to ErbB-2/neu in some patients suggests that this oncogene may be a useful target for vaccine therapy. We evaluated whether genetic immunization using dendritic cells (DC) transduced ex vivo with an adenovirus expressing the ErbB-2/neu gene (AdNeuTK) could induce protective and therapeutic immunity against a breast tumor cell line overexpressing ErbB-2/neu. Subcutaneous (s.c.) immunization with the DC vaccine elicited protective immunity in an average of 60% of animals. CTL analysis demonstrated specific cytotoxic activity against breast tumor cells, as well as syngeneic fibroblasts transduced with AdNeuTK. In vivo depletion studies demonstrated both CD4+ and CD8+ T cells were required. In a therapeutic setting, immunization with the DC vaccines could cure mice with pre-established tumors and efficacy was further enhanced by cotransducing DCs with a vector expressing murine IL-12 (AdmIL-12). These studies support DC vaccines as a therapeutic strategy for human breast cancer, while emphasizing the importance of optimizing an immune response by combining tumor antigen presentation with immunostimulatory cytokines.     

Helper T cell subsets for immunoglobulin A responses: oral immunization with tetanus toxoid and cholera toxin as adjuvant selectively induces Th2 cells in mucosa associated tissues

Antigen-specific B cell responses to mucosally delivered proteins are dependent upon CD4-positive T helper (Th) cells, and the frequency of Th1 and Th2 cell responses after oral immunization may determine the level and isotype of mucosal antibody responses. We have used a protein- based vaccine, tetanus toxoid (TT), together with the mucosal adjuvant cholera toxin (CT), for oral immunization of mice to study the nature of antigen-specific Th cell subsets induced in Peyer's patches (PP) of the gastrointestinal (GI) tract and in the spleen (SP) during peak antibody responses. Mice orally immunized with TT and CT responded with antigen-specific secretory immunoglobulin A (S-IgA) antibodies in the GI tract, and with both IgG and IgA antibody responses in serum. PP and SP CD4+ T cells from mice orally immunized with TT plus CT were cultured with antigen-coated latex microspheres for induction of proliferative responses and for enumeration of cytokine producing CD4+ T cells. Interestingly, both PP and SP CD4+ T cell cultures showed increased numbers of IL-4- and IL-5 (Th2-type)-producing, spot-forming cells (SFCs) after 21 d of immunization, while essentially no interferon-gamma (IFN-gamma) or IL-2 (Th1-type) SFCs were noted. Cytokine-specific Northern blots and RT-PCR also revealed that significant IL-4 and IL-5 mRNA levels, but not IFN-gamma or IL-2 mRNA, were present in CD4+ T cells isolated from antigen-stimulated cultures. However, systemic immunization with TT and CT induced antigen-specific IgG and IgM but not IgA antibodies in serum. Further, both IL-2 and IFN- gamma-producing Th1-type cells as well as IL-4- and IL-5-secreting Th2- type cells were generated in SP. Our results show that oral immunization with TT and the mucosal adjuvant CT selectively induced antigen-specific Th2-type responses which may represent the major helper cell phenotype involved in mucosal IgA responses in the GI tract.     

Polyelectrolyte LbL microcapsules versus PLGA microparticles for immunization with a protein antigen

The transition from organism-based traditional vaccines to the use of safer subunit vaccines has implemented the use of adjuvants to enhance immunogenicity. This study compares the potential of two types of polymeric microparticles as delivery systems for the model antigen ovalbumin. The delivery systems encompassed polyelectrolyte microcapsules, assembled via Layer-by-Layer technology, and PLGA microparticles fabricated by spray-drying. Mice were immunized subcutaneously either by a single injection or by two injections separated by four weeks with an equivalent dose of the OVA-loaded particles. Both particulate formulations mediated high, long-term IgG(1) responses whereas the IgG(2c) titers remained low. Additionally, Th1 and Th2 phenotype immune responses against OVA were assessed by quantifying the production of cytokines in CD4+ T-cells derived from the spleens of immunized mice at 6 months after the first injection. Immunization with particulate formulations led to significantly increased IL-2, IL-4, IL-10 and IFN-γ production by splenic CD4+ T-cells compared to control animals. LbL microcapsules and PLGA microparticles generated strong immune responses in vivo, characterized by a mixed Th1/Th2 type response with predominance of Th2 immunity. Both particulate formulations elicited a comparable type of immune response and appear to be promising for antigen delivery.     

Immunity to malaria elicited by hybrid hepatitis B virus core particles carrying circumsporozoite protein epitopes

The hepatitis B virus (HBV) nucleocapsid antigen (HBcAg) was investigated as a carrier moiety for the immunodominant circumsporozoite (CS) protein repeat epitopes of Plasmodium falciparum and the rodent malaria agent P. berghei. For this purpose hybrid genes coding for [NANP]4 (C75CS2) or [DP4NPN]2 (C75CS1) as internal inserts in HBcAg (between amino acids 75 and 81) were constructed and expressed in recombinant Salmonella typhimurium. The resulting hybrid HBcAg-CS polypeptides purified from S. typhimurium were particulate and displayed CS and HBc antigenicity, however, the HBc antigenicity was reduced compared to native recombinant HBcAg. Immunization of several mouse strains with HBcAg-CS1 and HBcAg-CS2 particles resulted in high titer, P.berghei- or P.falciparum-specific anti-CS antibodies representing all murine immunoglobulin G isotypes. The possible influence of carrier-specific immunosuppression was examined, and preexisting immunity to HBcAg did not significantly affect the immunogenicity of the CS epitopes within HBcAg-CS1 particles. Similarly, the choice of adjuvant did not significantly alter the immunogenicity of HBcAg-CS hybrid particles. Immunization in complete or incomplete Freund's adjuvant or alum resulted in equivalent anti-HBc and anti-CS humoral responses. Examination of T cell recognition of HBcAg-CS particles revealed that HBcAg-specific T cells were universally primed and CS-specific T cells were primed if the insert contained a CS-specific T cell recognition site. This indicates that the internal site in HBcAg is permissive for the inclusion of heterologous pathogen-specific T as well as B cell epitopes. Most importantly, 90 and 100% of BALB/c mice immunized with HBcAg-CS1 particles were protected against a P. berghei challenge infection in two independent experiments. Therefore, hybrid HBcAg-CS particles may represent a useful approach for future malaria vaccine development.     

A genetic immunization adjuvant system based on BVP22-antigen fusion.

DNA vaccines must induce a greater immune response to be effective in the biomedical industry. Therefore, we tested the trafficking trait of the bovine herpesvirus 1 (BHV-1) protein VP22 (BVP22) fused to an antigen and applied this unique trait to genetic immunization. DNA immunization with BVP22-antigen stimulates immune responses superior to that of standard DNA immunization. Mice were injected intramuscularly with gene constructs expressing the antigen yellow fluorescent protein (YFP), YFP fused to BVP22, or YFP fused to BHV-1 tegument protein VP16 (BVP16). The results revealed a significantly enhanced YFP antibody response with BVP22-YFP DNA immunization compared with either YFP or BVP16-YFP gene immunization. Notably, the BVP22-YFP DNA construct induced a stronger T helper 1 (Th1) response, based on IFN-gamma and IL-4 cytokine levels, and IgG2a/IgG1 ratios. Furthermore, BVP22-YFP genetic immunization induced a greater cytotoxic T lymphocyte response. The genetic adjuvant properties of BVP22 can make DNA vaccines much more effective clinically.     

Pharmaceutical and immunological evaluation of a single-dose hepatitis B vaccine using PLGA microspheres.

The objective of the study was to investigate the feasibility of a single-dose hepatitis B vaccine based on three kinds of poly (D, L)-lactide-co-glicolide acid (PLGA) microspheres. PLGA microspheres loaded with recombinant hepatitis B surface antigen (HBsAg) were formulated using a double emulsion microencapsulation technique. The pharmaceutical characteristics of size, surface morphology, protein loading efficiency, antigen integrity, release of HBsAg-loaded PLGA microspheres and degradation of the polymer in vitro were evaluated. The degradation of the polymer corresponded with the composition of the polymer (lactide/glycolide ratio), molecular weight of the polymer (viscosity) and morphology of the microspheres. These PLGA microspheres were able to continuously release antigen under conditions that mimic the environment in vivo. The single subcutaneous injection of HBsAg-loaded PLGA50/50 microspheres, PLGA75/25 microspheres and a mixture of PLGA50/50, PLGA75/25, and PLGA50/50-COOH microspheres in mice resulted in comparable serum antibody titers to those of three injections of the conventional aluminum adjuvant formulated HBsAg vaccine. Based on these findings in vitro and in vivo, it was concluded that HBsAg was successfully loaded into the PLGA microspheres, which can auto-boost an immune response, and the HBsAg-loaded PLGA microsphere is a promising candidate for the controlled delivery of a vaccine.     

The preS1 antigen of hepatitis B virus is highly immunogenic at the T cell level in man.

14 hepatitis B vaccine recipients who showed high titers of anti-hepatitis B surface antibodies in serum after booster immunization with a polyvalent hepatitis B surface antigen vaccine that contained trace amounts of hepatitis B virus (HBV) preS1 and preS2 envelope antigens were studied for their in vitro T cell response to these antigens. All 14 subjects displayed a significant proliferative T cell response to the S/p25 envelope region encoded polypeptide; 8 also responded to preS1, while only 1 showed a significant level of T cell proliferation to preS2. Limiting dilution analysis demonstrated that the frequency of preS-specific T cells in two of these vaccine recipients was higher than that of S/p25-specific T cells. T cell cloning was then performed and a total of 29 HBV envelope antigen-reactive CD4+ cloned lines were generated from two preS-responsive vaccines. 21 of these lines were S/p25 specific, 7 preS1 specific, and 1 preS2 specific. Taken together, all these results suggest that the preS1 antigen may function as a strong T cell immunogen in man.     

DNA immunization of neonates induces immunity despite the presence of maternal antibody.

Neonatal animals were not considered as suitable vaccine recipients either because of immune immaturity or because passively delivered antibody interferes with immune induction. In this report, we evaluated the response of neonatal mice to immunization with naked DNA encoding a herpes simplex virus (HSV) protein, and determined if maternally derived HSV antibody interfered with immunogenicity. Our results show that neonatal mice develop effective humoral and T cell responses after immunization with either DNA or inactivated vaccines. The nature of the responses to HSV immunization, however, was more Th2-like in neonates than in adults. Whereas neonatal mice from HSV-naive mothers responded well to both DNA and inactivated vaccines, only DNA immunization induced effective immunity in neonates born to immune mothers. Our results indicate that DNA vaccines might provide a useful means of immunizing young animals that still possess high levels of potentially interfering maternal antibody.     

Updates in Adult Immunizations

The Advisory Committee on Immunization Practices (ACIP) recommends that adults aged ≥19 years receive various vaccines to prevent serious health conditions, including hepatitis B, herpes zoster/shingles, human papilloma virus (HPV), and pneumonia. Recent vaccine approvals by the US Food and Drug Administration (FDA) have led to updates in the ACIP adult immunization schedule. This article provides a relevant clinical literature review for nurse practitioners on the newly approved vaccines for hepatitis B and herpes zoster and updated ACIP recommendations. In addition, recent FDA approval for expanded age of the HPV vaccine and updated ACIP recommendations for pneumococcal vaccines are discussed.     

A malaria vaccine candidate based on a hepatitis B virus core platform

OBJECTIVE: The recent success of a Plasmodium falciparum malaria vaccine consisting of circumsporozoite (CS) protein (CSP) T and B cell epitopes has rekindled interest in the development of a pre-erythrocytic vaccine. Our goal was to design an efficient delivery system for known neutralizing epitopes. METHODS: Well-characterized CSP-specific neutralizing B cell epitopes and a 'universal' T cell epitope were combined with a particulate carrier platform, the hepatitis B core antigen (HBcAg), to produce a novel pre-erythrocytic vaccine candidate. RESULTS: The vaccine candidate V12.PF3.1 is a potent immunogen in mice, eliciting unprecedented levels (greater than 106 titers) of sporozoite-binding antibodies after only two doses. The antisporozoite antibodies are long-lasting and represent all IgG isotypes, and antibody production is not genetically restricted. CSP-specific CD4+ T cells are also primed by V12.PF3.1 immunization in a majority of murine strains. Furthermore, the hybrid HBcAg-CS particles can be produced inexpensively in bacterial expression systems. CONCLUSION: These characteristics suggest that V12.PF3.1 represents an efficient and economical P. falciparum vaccine candidate for use separately or in combination with other formulations.     

2013年浙江省台州市儿童扩大国家免疫规划疫苗接种率调查

目的了解浙江省台州市常住儿童(本地及流动儿童)扩大国家免疫规划(national immunization program,NIP)疫苗接种现状。方法采用分层整群随机抽样的方法,全市9个县(市、区)随机抽取63个乡镇、126个村实际调查1954名本地儿童,入户开展问卷调查疫苗接种情况;随机选择流动人口聚集地实际调查256名流动儿童,面对面问卷调查疫苗接种情况。结果调查儿童建证(卡)率为99.95%。NIP基础免疫:1剂卡介苗(bacillus calmette-guerin,BCG)、3剂口服脊髓灰质炎减毒活疫苗(oral polio myelitis attenuated live vaccine,OPV)、3剂白喉破伤风百日咳(百白破)联合疫苗(diphtheria tetanus and pertussis combined vaccine,DTP)、1剂含麻疹成分疫苗(measles containing vaccine,MCV)接种率均95%,3剂乙型病毒性肝炎疫苗(hepatitis B vaccine,HepB)接种率均90%,五苗基础免疫全程免疫接种率为96.56%;NIP加强免疫:第4剂OPV(OPV4)、DTP(DTP4)、第2剂MCV(MCV2)和白破疫苗(tetanus and diphtheria toxoid childrens'dose vaccine,DT)接种率,除路桥区和仙居县外,其他县(市、区)接种率均90%;NIP新增疫苗A群脑膜炎多糖疫苗(group A meningococcal polysaccharide vaccine,MAPA)接种率,除三门县外,其他县(市)区均80%;流行性乙型脑炎(乙脑)疫苗(Japanese encephalitis vaccine,JEV)接种率,除路桥区、仙居县和三门县外,其他县(市)区均80%;甲型病毒性肝炎疫苗(hepatitis A vaccine,HepA)接种率均90%;A+C群脑膜炎多糖疫苗(group A+C meningococcal polysaccharide vaccine,MAP-A+C)接种率较低,全市2剂次接种率分别为87.19%和49.45%,且各县(市、区)接种率相差较大。NIP基础免疫BCG、OPV1、OPV3和DTP3,加强免疫OPV4、DTP4和MCV2及NIP新增疫苗流脑疫苗(MPV-A1-2和MPV-A+C1)和乙脑疫苗(JEV1-2),不同年龄组间差异均有统计学意义,呈现随年龄增加接种率降低的现象。NIP基础免疫BCG、DTP2、HepB1-2、HepB1和MCV1及时率,加强免疫MCV2、DTP4及NIP新增疫苗JEV2、MPV-A+C1-2,本地儿童与流动儿童间差异有统计学意义,本地儿童接种率高于流动儿童。结论 NIP非新增疫苗基础免疫和加强免疫均维持较高水平,但NIP新增疫苗接种率相对偏低。NIP非新增疫苗加强免疫和新增疫苗在不同年龄间和不同户籍儿童间差异有统计学意义,随年龄的增加,接种率呈现降低的趋势以及本地儿童接种率高于流动儿童的现象。     

Acute exacerbations of chronic type B hepatitis are accompanied by increased T cell responses to hepatitis B core and e antigens. Implications for hepatitis B e antigen seroconversion.

T cell proliferative responses to hepatitis B virus-encoded envelope antigen (S + preS2 + preS1), recombinant core antigen (HBcAg), and natural hepatitis B e antigen (HBeAg) were examined in 22 HBeAg-positive patients with chronic type B hepatitis and 17 healthy hepatitis B surface antigen (HBsAg) carriers. The results showed that HBeAg-positive patients had (a) higher levels of T cell responses to HBcAg/HBeAg than those of healthy HBsAg carriers (P less than 0.001 and P less than 0.01, respectively); (b) a further increase in these T cell responses during acute exacerbations (P less than 0.05 and P less than 0.05, respectively); (c) subsidence in the T cell responses to HBcAg/HBeAg after recovery from acute exacerbations and HBeAg seroconversion, whereas the responses would persist at high levels if the patients did not enter a clinical remission; and (d) low levels of T cell responses to S + preS2 + preS1 either before or after HBeAg seroconversion. The appearance of increasing T cell responses to HBcAg/HBeAg usually occurred in the early phase of acute exacerbations. These findings imply that HBcAg/HBeAg-specific T cells play an important role in the exacerbations of chronic hepatitis B and in HBeAg seroconversion. HBcAg/HBeAg-specific precursor T cell frequencies were serially studied in selected cases by limiting dilution assay. Elevation (two- to fourfold) of HBcAg/HBeAg-specific precursor T cell frequencies contributed to the increase of HBcAg/HBeAg-specific T cell proliferation during acute exacerbations.     

PEI - a potent,but not harmless,mucosal immuno-stimulator of mixed T-helper cell response and FasL-mediated cell death in mice

Polyethyleneimine (PEI) is one of the most effective gene delivery systems available today. However, very little is known about its ability to stimulate a systemic immune response and the molecular mechanisms thereof. However, this information is vital for the future development of new gene delivery systems. Here we address this issue by studying gene expression profiles from spleen lymphocytes after in vivo immunization of mice with PEI formulated with a reporter plasmid (PEI+) or the formulation alone (PEI-). PEI- was found to provoke the activation of genes with important immunostimulatory functions, but without the necessary costimulatory signals. PEI+ resulted in: a mixed Th1/Th2 response; activation of both CD8(+) and CD4(+) T cells, with a larger effect on CD4(+); and FasL-mediated antigen-induced cell death. A comparison of the immune responses of PEI+ with that of the clinically used tetanus toxoid-aluminum phosphate vaccine showed that the DNA vaccine provoked a stronger immune response as compared to the protein vaccine. However, many genes involved in other cellular responses such as apoptosis, stress responses and oncogenesis were activated in PEI+, supporting the theory of immunostimulation by danger genes, but also pointing toward possible adverse reactions such as Alzheimer's disease.     

Surfactant-free anionic PLA nanoparticles coated with HIV-1 p24 protein induced enhanced cellular and humoral immune responses in various animal models.

Microparticles and nanoparticles prepared with poly(D,L-lactide-co-glycolide) (PLGA) or poly(D,L-lactide) (PLA) polymers represent a promising method for in vivo delivery of encapsulated peptide, protein or DNA antigens. However, one major issue that limits the potential of these delivery systems is the instability or the degradation of the entrapped antigen. Charged microparticles carrying surface adsorbed antigen were developed to resolve this problem and appear more suitable for vaccine applications. We describe here new anionic PLA nanoparticles obtained by the dialysis method that are absolutely surfactant-free, which makes them more appropriate for use in humans. The potency of this delivery system as a vaccine carrier was tested in various animal models using HIV-1 p24 protein. p24-coated PLA nanoparticles (p24/PLA) induced high antibody titres (>10(6)) in mice, rabbits and macaques. Moreover, p24/PLA nanoparticles elicited strong CTL responses and a Th1-biased cytokine release (IFNgamma, IL-2) in mice. p24 protein seemed to generate a more Th1-oriented response when administered coated onto the surface of PLA nanoparticles than adjuvanted with Freund's adjuvant. Most importantly, the ability of p24/PLA particles to induce Th1 responses was also confirmed in the macaque model, since high levels of IFNgamma-producing CD4+ T cells and CD8+ T cells could be detected by the ELISPOT assay. This protein delivery system confirms the potential of charged nanoparticles in the field of vaccine development.     

Vaccination against hepatitis delta virus infection: studies in the woodchuck (Marmota monax) model

Hepatitis delta virus (HDV) superinfection of hepatitis B virus carriers causes severe liver disease and results in a high rate of chronicity. So far, neither sufficient therapy nor vaccines to prevent HBV carriers from superinfection are available. A good model to test vaccine candidates is the woodchuck chronically infected with the woodchuck hepatitis virus (WHV); the woodchuck can be superinfected with HDV and shows a course of infection similar to that of patients. Different strategies have been investigated to establish a protective vaccine against HDV superinfection. Both proteins of HDV (HDAg p24 and p27), which differ only in the C-terminal amino acid sequence, have been used as vaccine candidates. Synthetic peptides derived from B cell epitopes of HDAg and HDAg p24 expressed in Escherichia coli, yeast, or baculovirus have been used to immunize woodchucks. The protein immunization induced a specific antibody response, however, no protection from HDV superinfection was achieved. Vaccinations with vaccinia virus expressing HDAg p24 or p27 and DNA immunization with vectors expressing p24 were also not able to induce a protective immune response, but seemed to modulate the course of HDV superinfection. Thus, new strategies to develop a vaccine to prevent HDV superinfection are needed.     

Engerix-B hepatitis B vaccine (recombinant)/Smith, Kline & French.

Engerix-B [Hepatitis B Vaccine (Recombinant)], a product by SmithKline Biologicals, is a noninfectious recombinant DNA hepatitis B vaccine for immunization against infection caused by all known subtypes of hepatitis B virus. It provides a safe and well-tolerated vaccination regimen shown to confer immunity on the basis of anti-HBs antibody responses comparable with those of plasma-derived vaccines.