# Long-term persistence and boostability of immune responses following different rabies pre-exposure prophylaxis priming schedules of a purified chick embryo cell rabies vaccine administered alone or concomitantly with a Japanese encephalitis vaccine

## TL;DR

This study shows that a rabies vaccine provides long-term immunity for up to 10 years, with most people needing only one booster dose if needed.

## Contribution

The study demonstrates the long-term effectiveness and safety of rabies pre-exposure prophylaxis with or without a Japanese encephalitis vaccine.

## Key findings

- About 60-62% of participants had adequate rabies antibodies 10 years after vaccination without boosters.
- Most low responders needed only one booster dose to achieve protective antibody levels.
- The vaccine was safe and effective whether given alone or with a Japanese encephalitis vaccine.

## Abstract

Rabies pre-exposure prophylaxis (PrEP) is recommended to individuals at risk for exposure to rabies. Three intramuscular doses of the purified chick embryo cell (PCEC) rabies vaccine can be administered according to a conventional (four-week) or an accelerated (one-week) regimen.

This phase III, open-label study (NCT02545517) was an extension of the NCT01662440 study where immune responses of different primary PrEP regimens with PCEC rabies vaccine and Japanese encephalitis (JE) vaccine were assessed. Adults who had completed the parent study and received three doses of rabies PrEP regimens, concomitantly with a JE vaccine or alone (i.e., Rabies+JE-Accelerated, Rabies+JE-Conventional, and Rabies-Conventional groups) were enrolled in this extension study. Here we evaluated the long-term (up to 10 years after completing the primary vaccination) immunogenicity and boostability of PCEC rabies vaccine, and the safety of booster dose(s). Immunogenicity was assessed in terms of rabies virus neutralizing antibody (RVNA) concentrations, and titers ≥0.5 international units (IU)/mL were considered adequate for protection. Participants with RVNA concentrations <0.5 IU/mL were eligible for receiving PCEC rabies vaccine booster(s). Of the 459 participants enrolled in this study, 77.6% completed the trial. At the study end, the probability of detecting adequate RVNA concentrations in unboosted participants was 57.8%, 60.2%, and 62.0% for the Rabies+JE-Accelerated, Rabies+JE-Conventional, and Rabies-Conventional groups, respectively. Overall, 68.6% of all participants had RVNA concentrations ≥0.5 IU/mL at any timepoint and did not require a booster dose during the study follow-up period. Of the 144 participants with RVNA concentrations <0.5 IU/mL at any timepoint, 132 needed one booster dose throughout the follow-up period (Years 3–10) and 12 needed multiple booster administrations. No safety concerns were identified.

The PCEC rabies vaccine administered alone/concomitantly with the JE vaccine provides adequate immunity for up to 62% of unboosted participants at study end.

Pre-exposure prophylaxis (PrEP) with the purified chick embryo cell (PCEC) rabies vaccine is recommended to people at risk. We conducted a phase III, open-label study (NCT02545517) as an extension of the NCT01662440 study, where we assessed immune responses elicited by different primary PrEP regimens (accelerated [one-week] or conventional [four-week]) with PCEC rabies vaccine administered alone or concomitantly with the Japanese encephalitis vaccine. In the extension study, we evaluated the long-term immunogenicity and boostability of the PCEC rabies vaccine after PrEP administration in the parent study, over a period of 3–10 years from primary vaccination. At study end, 58–62% of unboosted participants had an adequate response to vaccination based on antibody levels. During the follow-up period, 68.6% of all participants did not require a booster dose and most low/non-responder vaccinees (132/144) needed a single booster dose to reach adequate antibody levels. The administration of a booster dose of PCEC rabies vaccine did not raise any safety concerns. The PCEC rabies vaccine provides immunity lasting for up to 10 years regardless of the primary schedule applied or if being administered alone or concomitantly with the Japanese encephalitis vaccine.