Phase 3 evaluation of a recombinant Hepatitis E vaccine: Immunogenicity, safety and public health implications

Phase 3 data presented at EASL 2026 highlight the potential of recombinant Hepatitis E vaccination to address a persistent global unmet need in viral hepatitis prevention.

Hepatitis E virus (HEV) remains a significant cause of acute viral hepatitis globally, with an increased risk of severe disease and mortality among pregnant women, immunocompromised individuals and patients with chronic liver disease(CLD).

In this interview, Prof. Premashis Kar (Maulana Azad Medical College, New Delhi, India) discusses the recombinant Hepatitis E vaccine, highlighting the design and immunogenicity and safety findings of the phase 3 study presented at EASL 2026, and considers the potential clinical and public health implications of expanded HEV vaccination strategies.

Abstract: A prospective, randomized, double-blind, placebo-controlled, phase III, multicenter study to evaluate the immunogenicity and safety of recombinant hepatitis-e vaccine in healthy adults & adolescents. EASL 2026, May 27–30, Barcelona, Spain.

touchIMMUNOLOGY coverage of EASL 2026

Could you describe the recombinant Hepatitis E vaccine and its role in prevention?

The recombinant Hepatitis E vaccine is developed using a genetically engineered fragment of the Hepatitis E virus (HEV) capsid protein. This protein stimulates the immune system to produce protective antibodies without causing disease. It is administered in 3 doses (0 month, 1 month & 6 month) and has shown high efficacy in preventing HEV infection.

The recombinant Hepatitis E vaccine has demonstrated high efficacy in clinical studies. In large phase 3 trials, it has showed approximately 95–100% efficacy in preventing symptomatic Hepatitis E infection after the full three-dose schedule. Long-term follow-up studies indicate sustained protection for at least 10 years, with evidence of persistent antibodies.

The vaccine plays a crucial role in reducing the risk of outbreaks, especially in endemic regions and high-risk groups, such as pregnant women, people with chronic liver disease or immunocompromised individuals. By preventing infection, the vaccines helps lower complications, hospitalizations, and mortality associated with Hepatitis E.

What were the aims and design of the phase 3 study evaluating the recombinant hepatitis E vaccine?

This was a prospective, randomized, double-blind, placebo-controlled, multicentre phase 3 study evaluating the immunogenicity and safety of three doses of purified recombinant Hepatitis E vaccine (E. coli) compared with matching placebo in healthy Indian adults and adolescents.

The primary objective was to assess immunogenicity based on the seroconversion rate from baseline to 1 month after administration of the third dose. The secondary objective was to assess immunogenicity based on the mean change in geometric mean titre (GMT) of anti-HEV antibodies from baseline to 1 month after administration of the third IP dose. Safety was assessed using solicited and unsolicited adverse events following immunization (AEFI).

What were the key findings on vaccine immunogenicity?

At day 211+14 visit, a statistically significant (p value: <0.001) seroconversion was observed between the treatment groups in both the intention-to-treat (ITT; vaccine arm [75%] and placebo arm [18%]) and per-protocol (PP; vaccine arm [89%] and placebo arm [22%]) populations. A statistically significant (p value: <0.0001) mean change in the geometric mean titer was observed between the treatment groups in both the ITT (vaccine arm [3.17] and placebo arm [0.15]) and PP (vaccine arm [3.68] and placebo arm [0.13]) populations when compared to the baseline visit.

What was the safety & tolerability profile observed in the study?

A total of 29 adverse events (AEs) in 13 subjects were reported. Most of the AEs were resolved without sequalae. The most common AE reported was headache followed by pyrexia, eosinophilia and fatigue. No serious adverse events or deaths were reported. The study drug was well tolerated. No clinically significant findings were reported during the laboratory report review, vitals measurement and general examination.

What could be the clinical and public health impact of these findings?

Th clinical impact is that the vaccine offers strong protection against Hepatitis E infection, reducing the risk of acute hepatitis, liver failure, and complications—especially in high-risk groups like pregnant women, those with CLD or immunocompromised individuals, where mortality can be significant. It can decrease hospitalizations, improve patient outcomes, and reduce the burden on healthcare systems.

In terms of a public health impact, widespread use can help prevent outbreaks in endemic regions, interrupt transmission, and lower disease incidence. It supports targeted immunization strategies (e.g., in outbreaks or vulnerable populations) and could potentially justify inclusion in national immunization programs, leading to long-term reduction in morbidity and mortality.