A recent international study has revealed that the HepB-CpG vaccine, known commercially as Heplisav-B, offers enhanced protection against hepatitis B virus (HBV) in people living with HIV who did not respond to prior vaccinations. The phase 3 BEe-HIVe trial demonstrated that HepB-CpG induced a protective antibody response in a significantly higher percentage of participants compared to the older HepB-alum vaccine (Engerix-B). This finding, published in JAMA, suggests a potential new strategy for protecting a vulnerable population at high risk of HBV infection and its complications.
Superior Antibody Response with HepB-CpG
The study, led by Dr. Kristen Marks, an associate professor of medicine at Weill Cornell Medicine, found that HepB-CpG induced protective levels of antibodies in up to 99.4% of participants receiving a three-dose regimen, and 93.1% receiving a two-dose regimen. In contrast, only 80.6% of participants who received the HepB-alum vaccine achieved similar protection. This marked difference highlights the potential of HepB-CpG to overcome the impaired immune response often seen in people with HIV.
"These results suggest a potential path forward for the large number of people living with HIV who can’t get protection from older hepatitis B vaccines," said Dr. Marks.
The BEe-HIVe Trial: A Detailed Look
The NIH-sponsored BEe-HIVe (B-Enhancement of HBV Vaccination in Persons Living With HIV) trial enrolled 561 participants at 40 sites across North and South America, Africa, and Asia. All participants had a history of prior hepatitis B vaccination but lacked protective antibody levels. The trial compared three vaccine regimens: a three-dose schedule of HepB-CpG, a two-dose schedule of HepB-CpG, and a three-dose schedule of HepB-alum.
Both HepB-CpG regimens demonstrated superior performance compared to the HepB-alum vaccine. The study defined a protective antibody response as a concentration of anti-HBsAg ≥10 mIU/mL. The difference in seroprotection rates between the HepB-CpG and HepB-alum arms was statistically significant (p<0.001 for both comparisons).
Hepatitis B and HIV: A Dangerous Combination
Hepatitis B is primarily transmitted through bodily fluids and can lead to chronic liver infection, cirrhosis, and liver cancer. The World Health Organization estimates that over 250 million people worldwide live with chronic hepatitis B infection, resulting in over a million deaths annually. People with HIV are particularly vulnerable due to their compromised immune systems, which can limit their ability to clear the virus or mount an effective immune response to vaccination. In the United States, an estimated 5-10% of people living with HIV also have hepatitis B.
Clinical Implications and Future Directions
The United States Food and Drug Administration (FDA) approved HepB-CpG for use in adults in 2017. These new findings support the use of HepB-CpG as the preferred vaccine for boosting immunity against hepatitis B in adults with HIV who have little or no existing antibody protection. Prior research has also shown that Heplisav-B is highly effective in patients with diabetes or end-stage kidney disease, who often respond poorly to traditional hepatitis B vaccines.
The trial did not reveal any new safety concerns associated with HepB-CpG. Dr. Marks and her team are currently conducting a follow-up analysis to assess the durability of the antibody responses induced by the vaccine.
