It was with great interest that we read Clinical Trial: Immunogenicity of Double-Dose Versus Standard-Dose of Hepatitis B Virus Vaccine in Inflammatory Bowel Disease by Singh et al. 1 In their study comparing the immunogenicity of standard-dose versus double-dose Engerix-B hepatitis B virus (HBV) vaccination in patients with inflammatory bowel disease (IBD), adequate immune response (88.4% vs. 55.6%) and effective immune response (69.8% vs. 46.7%) rates were significantly higher with the double-dose. These findings highlight that modification of vaccine dose can improve seroprotection using a conventional recombinant vaccine. However, dose escalation alone has important limitations: some immunosuppressed patients still fail to seroconvert, the three-dose schedule remains prolonged, the cost per patient increases, and higher antigen quantity does not address innate immune activation. A recent letter by Bertin et al. responding to the Singh et al. study highlighted the importance of exploring adjuvanted vaccines such as Heplisav-B HepB-cytidine phospho-guanosine (CpG) in patients with IBD, further underscoring the need for strategies beyond double-dose recombinant vaccination 2. HepB-CpG is a 2-dose adjuvanted recombinant HBV vaccine series approved by the U.S. Food and Drug Administration (FDA) in 2017 that is more immunogenic in the general adult population 3, 4. Since its approval by the FDA, it has become available in the United Kingdom, the European Union, and Canada. It is unique in that it incorporates a novel adjuvant that binds to Toll-like receptor 9, increasing the immune response to HBsAg 5. Studies on HepB-CpG in patients with IBD have demonstrated seroprotection rates of 72%–78% compared to seroprotection rates of 36%–80% with Engerix-B 6-8. Our recent study showed no significant difference in seroprotection rates with HepB-CpG in patients with IBD who are on biologic therapy compared to those who are not, with 49 (58%) on immunosuppressive therapy and 22 (26%) who were primary HBV vaccine non-responders 8. Although patients who were previous primary nonresponders were less likely to respond to HepB-CpG when compared to those who were HBV vaccine naïve, there was a benefit in a third dose 7, 8. These results demonstrate that HepB-CpG is effective in patients with IBD, cost effective due to its 2-dose schedule, and a third dose may provide benefit in those who initially don't respond. Vaccination history is essential in those not seroprotected. Those who completed a prior vaccine series should receive a challenge dose to evaluate for an anamnestic response as immune memory may persist despite undetectable antibody levels 9. In a study with 168 HBV-vaccinated patients with IBD, 71% initially demonstrated sustained seroprotection. Of the 48 patients with anti-HBs < 10 mIU/mL, 34 responded to a challenge dose, yielding an overall seroprotection rate of 92% 9. We outline an optimal immunization strategy for patients with IBD (Figure 1). Singh et al. demonstrated that double-dose Engerix-B improves seroprotection, but some still fail to respond, and the 3-dose schedule may limit adherence. We suggest vaccination with HepB-CpG given high seroprotection rates, cost-effectiveness and a 2-dose schedule. A third dose may be given to nonresponders to increase seroprotection rates. Yash Hegde: writing – original draft, writing – review and editing. Freddy Caldera: writing – original draft, writing – review and editing. The authors have nothing to report. Dr. Freddy Caldera received research support from Takeda Pharmaceuticals, Janssen, and Novavax. He consulted for Takeda, Janssen and GSK. This article is linked to Singh et al. paper. To view this article, visit https://doi.org/10.1111/apt.70470. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
Hegde et al. (Tue,) studied this question.