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.

<h4>Background</h4>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-wee...

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Main Authors: Tomas Jelinek, Mirjam Schunk, Emil C Reisinger, Marylyn M Addo, Ursula Wiedermann, Marco Costantini, Maria Lattanzi, Michele Pellegrini, Ilaria Galgani, Rabies-018 V49_23E1 study group
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Language:English
Published: Public Library of Science (PLoS) 2025-05-01
Series:PLoS Neglected Tropical Diseases
Online Access:https://doi.org/10.1371/journal.pntd.0013118
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author Tomas Jelinek
Mirjam Schunk
Emil C Reisinger
Marylyn M Addo
Ursula Wiedermann
Marco Costantini
Maria Lattanzi
Michele Pellegrini
Ilaria Galgani
Rabies-018 V49_23E1 study group
author_facet Tomas Jelinek
Mirjam Schunk
Emil C Reisinger
Marylyn M Addo
Ursula Wiedermann
Marco Costantini
Maria Lattanzi
Michele Pellegrini
Ilaria Galgani
Rabies-018 V49_23E1 study group
author_sort Tomas Jelinek
collection DOAJ
description <h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusion/significance</h4>The PCEC rabies vaccine administered alone/concomitantly with the JE vaccine provides adequate immunity for up to 62% of unboosted participants at study end.
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spelling doaj-art-83bf216ba1354d09b270f91c6abff05a2025-08-20T02:39:44ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352025-05-01195e001311810.1371/journal.pntd.0013118Long-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.Tomas JelinekMirjam SchunkEmil C ReisingerMarylyn M AddoUrsula WiedermannMarco CostantiniMaria LattanziMichele PellegriniIlaria GalganiRabies-018 V49_23E1 study group<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusion/significance</h4>The PCEC rabies vaccine administered alone/concomitantly with the JE vaccine provides adequate immunity for up to 62% of unboosted participants at study end.https://doi.org/10.1371/journal.pntd.0013118
spellingShingle Tomas Jelinek
Mirjam Schunk
Emil C Reisinger
Marylyn M Addo
Ursula Wiedermann
Marco Costantini
Maria Lattanzi
Michele Pellegrini
Ilaria Galgani
Rabies-018 V49_23E1 study group
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.
PLoS Neglected Tropical Diseases
title 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.
title_full 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.
title_fullStr 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.
title_full_unstemmed 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.
title_short 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.
title_sort 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
url https://doi.org/10.1371/journal.pntd.0013118
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