Immunogenicity and safety of a tri-antigenic versus a mono-antigenic hepatitis B vaccine in adults (PROTECT): a randomised, double-blind, phase 3 trial

Vesikari, Timo; Langley, Joanne M.; Segall, Nathan; Ward, Brian J.; Cooper, Curtis; Poliquin, Guillaume; Smith, Bruce R.; Gantt, Soren; McElhaney, Janet E.; Dionne, Marc; Damme, Pierre Van; Leroux-Roels, Isabel; Leroux‐Roels, Geert; Machluf, Nathalie; Spaans, Johanna N.; Yassin-Rajkumar, Bebi; Anderson, David E.; Popovic, Vlad; Díaz‐Mitoma, Francisco; Rankin, Bruce; Griffin, Carl; Turner, Mark S.; Kirstein, Judith; Rizzardi, Barbara; Williams, Hayes; Ahonen, Anitta; Henriksson, Olli; Ukkonen, Benita; Paassilta, Marita

doi:10.1016/s1473-3099(20)30780-5

Cited by 48 publications

(68 citation statements)

References 22 publications

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“…The higher reactogenicity of 3A-HBV noted in this study, which was mostly of mild or moderate severity and short duration, is consistent with the safety profile known from previous clinical trials of 3A-HBV 15,18,19,27 and postmarketing experience. Completion of the 3-dose schedule for 3A-HBV was high (93.0%), and study discontinuation due to SAEs or AEs was rare (0.4%).…”

Section: Discussionsupporting

confidence: 90%

“…T-helper epitopes in the pre-S1/S2 domains overcome genetic nonresponsiveness to induce antibodies to S. 22,23 Also, 3A-HBV is produced in mammalian CHO cells, which are used extensively in safe human biologics production 24 ; and unlike yeast-derived 1A-HBV, 3A-HBV has a mammalian protein folding and glycosylation pattern that enhances vaccine immunogenicity. 25 The SPRs reported for 3A-HBV following a 3-dose regimen in this study (99.3%) are slightly higher than those reported in PROTECT (91.4%), 15 which enrolled individuals aged 18 to 90 years in stable health, including those with well-controlled chronic conditions. Of note, the SPR in age subgroup of those aged 18 to 44 years in PROTECT (99.2%) 15 was almost identical to overall SPR of the pooled 3A-HBV in this study's participants, who were aged 18 to 45 years (99.4%).…”

Section: Discussionmentioning

confidence: 52%

“…The 3A-HBV vaccine is a recombinant, 3-antigen vaccine that has shown, in clinical trials, to induce high antibody concentrations resulting in high SPRs 15,18,19,28 against HBV, which can cause a lifelong chronic infection with a high risk of liver fibrosis, cirrhosis, and hepatocellular carcinoma if left untreated. The 3A-HBV vaccine has been shown to achieve high SPRs and induce anti-HBs concentrations across diverse healthy adult populations in Asia, Europe, and North America 15,17,19 and also in key subgroups of older adults with poor or delayed responses to standard-of-care HBV vaccines. 15 JAMA Network Open | Infectious Diseases Limitations…”

Section: Discussionmentioning

confidence: 99%

“…The 3A-HBV vaccine has been shown to achieve high SPRs and induce anti-HBs concentrations across diverse healthy adult populations in Asia, Europe, and North America 15,17,19 and also in key subgroups of older adults with poor or delayed responses to standard-of-care HBV vaccines. 15 JAMA Network Open | Infectious Diseases Limitations…”

Section: Discussionmentioning

confidence: 99%

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Immunogenicity and Safety of a 3-Antigen Hepatitis B Vaccine vs a Single-Antigen Hepatitis B Vaccine

Vesikari¹,

Finn

Damme

et al. 2021

JAMA Netw Open

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IMPORTANCEThere is a need for improved immunogenicity of hepatitis B virus (HBV) vaccines among young adults with risk of infection.OBJECTIVES To demonstrate manufacturing equivalence of a 3-antigen (3A) HBV vaccine, evaluate noninferiority of seroprotection rate (SPR) of 3A-HBV vs single-antigen (1A) HBV after 2 and 3 vaccine doses, and compare safety and reactogenicity between 3A-HBV and 1A-HBV vaccines. DESIGN, SETTING, AND PARTICIPANTSThis phase 3, double-blinded, randomized clinical trial included healthy adults aged 18 to 45 years randomized to 1 of three 3A-HBV groups or 1 control group receiving 1A-HBV. The trial was conducted at 37 community clinics and academic hospitals in Canada, Europe, the United Kingdom, and the United States between December 2017 and October 2019. Participants were followed up for 48 weeks after the first vaccination. INTERVENTIONS Intramuscular administration of 3A-HBV (10 μg) or 1A-HBV (20 μg) on days 0, 28, and 168. MAIN OUTCOMES AND MEASURES Geometric mean concentration (GMC) of serum hepatitis Bsurface antibodies (anti-HBs) and proportion of participants achieving seroprotection. RESULTSOf 2838 participants, 1638 (57.8%) were women, 2595 (91.5%) were White, and 161(5.7%) were Black or African American. A total of 712 participants (25.1%) were randomized to the 1A-HBV group and 2126 (74.9%) to 3A-HBV. The mean (SD) age at informed consent was 33.5 (8.0) years. The study demonstrated 3A-HBV lot-to-lot consistency, as the 2-sided 95% CIs for each pairwise comparison for the anti-HBs GMC ratios were within 0.67 and 1.50 (eg, adjusted GMC ratio,

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Immunogenicity and Safety of a 3-Antigen Hepatitis B Vaccine vs a Single-Antigen Hepatitis B Vaccine

Vesikari¹,

Finn

Damme

et al. 2021

JAMA Netw Open

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“…Taken together, the importance of MHBs for hepatitis B vaccine development has been emphasized in clinical trial [ 42 ]. Although disease activity and monitoring of treatment response in CHB patients can be predicted through the quantification of HBsAg [ 25 , 43 , 44 ], the biological function of MHBs remains largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B virus middle surface antigen loss promotes clinical variant persistence in mouse models

Lin

Xie

et al. 2021

Virulence

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Longitudinal mapping of hepatitis B vaccine‐induced B‐cell linear epitopes in healthy individuals

Zhong

Liu

Zhou

et al. 2022

Journal of Medical Virology

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The elimination of hepatitis B virus (HBV) infection is partially facilitated by the prophylactic HB vaccine. As the loss of seroprotection over time remains a conundrum for long‐lasting protection, a comprehensive dynamic analysis of immunogenic targets of the HB vaccine will provide novel insights into the improvement and design of potential targets. In this study, 36 healthy subjects without prior history of hepatitis B infection and negative for hepatitis B surface antibody (anti‐HBs) were enrolled. Participants were given a series of three doses of HB vaccine on a 0‐, 1‐, and 6‐month schedule and longitudinally followed up. We systematically mapped 55 overlapping 15‐mer peptides covering the small S protein of hepatitis B virus (SHBs) of vaccinees' serum samples at seven time points by performing an ELISA assay. Additionally, the frequencies and function dynamics of adaptive immune response were assessed by flow cytometry. We found that the SHBs peptide coverage presented an overall upward trend along with the vaccination progress, and the individual subpartition recognition was strongly correlated with the anti‐HBs titers. Moreover, we identified one dominant epitope (S29) located on “a determinant region” associated with effective vaccine response. Besides, significant correlations between the proportion of plasmablasts and proliferating B cells and levels of anti‐HBs were ascertained. Taken together, our data characterized the dynamics of HB vaccine‐induced neutralizing antibodies against B‐cell linear epitopes on SHBs and adaptive immune response, which will be constructive to develop the next‐generation vaccine.

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Immunogenicity and safety of a tri-antigenic versus a mono-antigenic hepatitis B vaccine in adults (PROTECT): a randomised, double-blind, phase 3 trial

Cited by 48 publications

References 22 publications

Immunogenicity and Safety of a 3-Antigen Hepatitis B Vaccine vs a Single-Antigen Hepatitis B Vaccine

Immunogenicity and Safety of a 3-Antigen Hepatitis B Vaccine vs a Single-Antigen Hepatitis B Vaccine

Hepatitis B virus middle surface antigen loss promotes clinical variant persistence in mouse models

Longitudinal mapping of hepatitis B vaccine‐induced B‐cell linear epitopes in healthy individuals

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