Immunogenicity and safety of an investigational hepatitis B vaccine with a Toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared with a licensed hepatitis B vaccine in patients with chronic kidney disease and type 2 diabetes mellitus

Janssen, Julia M.; Heyward, William L.; Martin, Jacob T.; Janssen, Robert S.

doi:10.1016/j.vaccine.2014.12.060

Cited by 35 publications

(20 citation statements)

References 8 publications

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“…In vivo stimulation of TLR9 is also an envisaged strategy in the fields of cancer and infectious disease therapies (15,16). TLR9 ligands (TLR9-L) are likely to be used in the HBV field as adjuvants for HBV vaccination (17)(18)(19) but have also been recently shown to induce an antiviral activity in animal models of HBV infection (20)(21)(22). However, regarding the latter, the antiviral effect obtained in the woodchuck model with a TLR9-L seems to be far less potent than that obtained with GS-9620 (14,22).…”

mentioning

confidence: 99%

Interaction between Toll-Like Receptor 9-CpG Oligodeoxynucleotides and Hepatitis B Virus Virions Leads to Entry Inhibition in Hepatocytes and Reduction of Alpha Interferon Production by Plasmacytoid Dendritic Cells

Aillot

Bonnin

Ait-Goughoulte

et al. 2018

Antimicrob Agents Chemother

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We previously reported that Toll-like receptor 9 (TLR9)-CpG oligonucleotides could inhibit the establishment of hepatitis B virus (HBV) infections in hepatocytes. Our aim was to uncover the underlying mechanisms of this inhibition. HepaRG cells, RPMI-B lymphoblastoma cells, and primary plasmacytoid dendritic cells (pDCs) exposed to HBV and TLR9 ligands/agonists in various configurations were used. We observed an inhibition of HBV infection upon TLR9 stimulations only when agonist was applied during inoculation. This inhibition was independent of interleukin-6 (IL-6)/interferon-inducible protein 10 (IP-10) production as well as of TLR9 expression in hepatocytes. We further demonstrated an entry inhibition mechanism by showing a noncovalent binding of TLR9 agonist to HBV particles. Besides inhibiting HBV entry into hepatocytes, this biophysical interaction between HBV virions and TLR9 agonist was responsible for a reduction of alpha interferon (IFN-α) expression by pDCs. Interestingly, subviral particles composed of only HBsAg were able to genuinely inhibit the TLR9 pathway, without titrating TLR9 ligands. To conclude, our data suggest that synthetic TLR9-CpG oligonucleotides can strongly inhibit HBV entry by "coating" HBV virions and thereby preventing their interaction with cellular receptor. This titration effect of TLR9 agonist is also artifactually responsible for the inhibition of TLR9 engagement in pDCs, whereas a genuine inhibition of this innate pathway was confirmed with HBsAg subviral particles.

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confidence: 99%

Interaction between Toll-Like Receptor 9-CpG Oligodeoxynucleotides and Hepatitis B Virus Virions Leads to Entry Inhibition in Hepatocytes and Reduction of Alpha Interferon Production by Plasmacytoid Dendritic Cells

Aillot

Bonnin

Ait-Goughoulte

et al. 2018

Antimicrob Agents Chemother

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“…After reviewing full text, 13 publication were excluded, among which nine articles did not contain an adequate methodology description in randomisation and blind methods, one article was without HBsAg-Eng as a control group [15], one article had an obscure vaccination schedule and difficulty in extracting relevant data [16], and two articles had data that could not be obtained from figures or tables [17,18]. For using raw data from same the RCTs, two articles were excluded [19,20]. Eventually, four RCTs were included in our meta-analysis [21][22][23][24].…”

Section: Study Screeningmentioning

confidence: 99%

Comparative analysis of the safety and efficacy of HBsAg-1018 versus HBsAg-Eng: a meta-analysis

Zhang¹,

Guo²,

Duan³

2019

cejoi

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Introduction: In addition to alum adjuvant, a wide diversity of adjuvants have been developed to enhance immune response of hepatitis B virus (HBV) vaccine in varying subjects, either in healthy vaccinators or subjects with hypo-immunity. In this context, a novel HBV vaccine HBsAg-1018, formulated with a toll-like receptor 9 agonist, was developed, and is currently in the phase of clinical trials. So, the first meta-analysis was performed to examine the safety and immune response of HBsAg-1018 among varying subjects. Material and methods: On the basis of inclusion criterion, eligible studies that reported safety and immunogenicity induced by HBsAg-1018 vaccination in randomised, controlled trials (RCTs) were involved from three databases: PubMed, EMBASE, and the Cochrane Library, and further confirmed by two reviewers. Meta-analysis was conducted using RevMan 5.3. The pooled relative risk (RR) for safety and immunogenicity was calculated using random-effects or fixed-effects models according to the heterogeneity of included studies. The methodology quality of eligible studies was assessed using the Cochrane Handbook for Systematic Reviews of Interventions version 5.1.0. Results: In total 5073 subjects administrated with HBV vaccine from four eligible publications were included in this meta-analysis. The data related to immunogenicity and safety post vaccination were pooled for meta-analysis. For safety, the combined RRs for adverse reactions were 0.98

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“…The newly approved Heplisav-B, featuring CpG adjuvant, has proven more immunogenic than the older HBV vaccines in groups with reduced immune function such as the elderly, those who have diabetes and chronic kidney disease, and possibly in persons living with HIV[52–54]. The vaccine has no published experience in SLE patients .…”

Section: _hepatitis B Vaccinementioning

confidence: 99%

Recommendations and barriers to vaccination in systemic lupus erythematosus

Garg

Mufti

Palmore

2018

Autoimmunity Reviews

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Patients with Systemic Lupus Erythematosus (SLE) pose a unique dilemma pertaining to immunization against common pathogens. SLE patients are usually not immunized with vaccines based on the fear of either precipitating infection in this immunosuppressed patient population (with live vaccines) or aggravating autoimmunity and hence lupus flares (with any vaccines). However, elevated vulnerability to infection makes patients with SLE precisely the population that needs protection from vaccine-preventable diseases. A summary of guidelines from the Centers for Disease Control and Prevention, professional societies, review articles and expert opinions regarding use of individual vaccines applicable to adults with SLE is presented in this review.

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Immunogenicity and safety of an investigational hepatitis B vaccine with a Toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared with a licensed hepatitis B vaccine in patients with chronic kidney disease and type 2 diabetes mellitus

Cited by 35 publications

References 8 publications

Interaction between Toll-Like Receptor 9-CpG Oligodeoxynucleotides and Hepatitis B Virus Virions Leads to Entry Inhibition in Hepatocytes and Reduction of Alpha Interferon Production by Plasmacytoid Dendritic Cells

Interaction between Toll-Like Receptor 9-CpG Oligodeoxynucleotides and Hepatitis B Virus Virions Leads to Entry Inhibition in Hepatocytes and Reduction of Alpha Interferon Production by Plasmacytoid Dendritic Cells

Comparative analysis of the safety and efficacy of HBsAg-1018 versus HBsAg-Eng: a meta-analysis

Recommendations and barriers to vaccination in systemic lupus erythematosus

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