Real World Considerations for Heplisav-B Use in Spanish Primary Care for Mobile and Underserved Populations

Dear Editor,

We read with great interest the recent article by Williams and Newman (1) comparing the effectiveness of Heplisav-B and standard hepatitis B vaccines as boosters among previously vaccinated health care workers with insufficient anti-HBs titers (<10 mIU/mL). The authors present compelling evidence indicating that Heplisav-B offers a significantly higher seroprotection rate following a single booster dose compared to traditional vaccines. These findings have important implications for clinical practice, especially within the context of primary care settings in Spain, where many health care workers, particularly those involved in community-based and primary care services, frequently encounter situations of uncertain seroprotection.

One relevant aspect highlighted by Williams and Newman pertains to the potential application of Heplisav-B within post-exposure scenarios. Although the study itself was retrospective and not designed specifically to evaluate post-exposure prophylaxis, the demonstrated rapid and robust immune response achieved by Heplisav-B suggests a promising role in these critical situations. Current Spanish protocols for post-exposure prophylaxis (PEP) after occupational exposure typically involve hepatitis B immunoglobulin (HBIG) administration alongside standard vaccine schedules (2). However, adherence and completion of a traditional three-dose vaccine schedule often pose logistical and adherence challenges, particularly in primary care centers, where monitoring follow-up vaccinations is complex due to high patient volumes and limited staffing. In this context, the two-dose regimen of Heplisav-B, administered one month apart, might substantially enhance compliance and simplify vaccination follow-up, thereby reducing the administrative and clinical burden on health services and potentially increasing overall vaccination efficacy.

Furthermore, considering the strong immune response elicited by the CpG-adjuvanted vaccine, Heplisav-B might offer distinct advantages over traditional vaccination strategies when dealing with populations characterized by inconsistent medical follow-up, such as migrants, people experiencing homelessness, or individuals with substance use disorders. Several studies have consistently reported lower vaccination coverage rates and incomplete vaccination schedules among these vulnerable groups, largely due to barriers such as frequent changes of residence, irregular engagement with health services, and competing priorities (3). A shorter vaccination regimen and more rapid development of immunity, as offered by Heplisav-B, could meaningfully improve hepatitis B protection rates in these populations. This is particularly pertinent for primary care providers in Spain, who frequently manage such vulnerable groups and are responsible for implementing preventive health measures and vaccination campaigns. The recent European Medicines Agency (EMA) approval of Heplisav-B supports its broader implementation within vaccination policies tailored specifically to these high-risk populations.

Finally, it is prudent to remain cautious about generalizing these findings beyond the specific demographic included in Williams and Newman's study—young, healthy adults primarily drawn from military health education settings. Real-world primary care populations in Spain often exhibit greater demographic and clinical heterogeneity, including older health care workers, individuals with chronic health conditions, and diverse ethnic backgrounds, all of which might influence vaccine responsiveness. Studies have documented variations in immunogenicity associated with age, comorbidities, and other immunological factors (4–6). Thus, replicating and validating these results within broader, more diverse populations is necessary to confirm the generalizability of the study's conclusions.

In our opinion, Williams and Newman's findings provide valuable preliminary evidence supporting the integration of Heplisav-B into existing hepatitis B vaccination strategies, particularly in primary care and community health contexts. Considering the potential simplification of vaccine regimens and improved adherence, this could enhance protection among health care workers and vulnerable populations alike. However, further prospective, multicenter studies conducted explicitly in primary care settings across Europe—including Spain—are necessary to confirm these promising initial findings and inform clinical and public health practice.

REFERENCES:

1. Williams AL, Newman RS. Heplisav-B vs Standard Hepatitis B Vaccine Booster for Health Care Workers. Ann Fam Med. 2025 Mar 1;23(2):162–4.

2. Jiménez EMA, Miró O, Blanco JR, Moreno D, Dueñas C, Platón EM, et al. Documento de Consenso sobre Profilaxis Postexposición Ocupacional y No Ocupacional en Relación con el VIH, VHB y VHC en Adultos y Niños. Rodríguez RP, Lozano F, Castro PG de, editors. Secretaría del Plan Nacional sobre el Sida (SPNS), GeSIDA, SEMST, SEMPSPH, AEEMT, SESLAP, ANMTAS, SEIP, SEMES, GEHEP, FEDEET; 2015.

3. Badiaga S, Raoult D, Brouqui P. Preventing and Controlling Emerging and Reemerging Transmissible Diseases in the Homeless. Emerg Infect Dis. 2008 Sep;14(9):1353–9.

4. Yang S, Tian G, Cui Y, Ding C, Deng M, Yu C, et al. Factors influencing immunologic response to hepatitis B vaccine in adults. Sci Rep. 2016 Jun 21;6(1):27251.

5. Weinbaum C, Billah K, Mast E. Hepatitis B Vaccination Coverage Among Adults–United States, 2004. JAMA J Am Med Assoc. 2006;296(1).

6. Schillie S. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep [Internet]. 2018 [cited 2025 Apr 18];67. Available from: https://www.cdc.gov/mmwr/volumes/67/rr/rr6701a1.htm