Dataset Information

Proof-of-concept of a low-dose unmodified mRNA-based rabies vaccine formulated with lipid nanoparticles in human volunteers: A phase 1 trial.

ABSTRACT:

Introduction

In a first-in-human study immune responses to rabies virus glycoprotein (RABV-G)-mRNA vaccine were dependent on the route of administration, necessitating specialized devices. Following successful preclinical studies with mRNA encapsulated in lipid nanoparticles (LNP), we tested an mRNA-LNP formulation (CV7202).

Methods

In this phase 1, multi-center, controlled study in Belgium and Germany we enrolled 55 healthy 18-40-year-olds to receive intramuscular injections of 5 ?g (n = 10), 1 ?g (n = 16), or 2 ?g (n = 16) CV7202 on Day 1; subsets (n = 8) of 1 ?g and 2 ?g groups received second doses on Day 29. Controls (n = 10) received rabies vaccine, Rabipur, on Days 1, 8 and 29. Safety and reactogenicity were assessed up to 28 days post-vaccination using diary cards; immunogenicity was measured as RABV-G-specific neutralizing titers (VNT) by RFFIT and IgG by ELISA.

Results

As initially tested doses of 5 ?g CV7202 elicited unacceptably high reactogenicity we subsequently tested 1 and 2 ?g doses which were better tolerated. No vaccine-related serious adverse events or withdrawals occurred. Low, dose-dependent VNT responses were detectable from Day 15 and by Day 29%, 31% and 22% of 1, 2 and 5 ?g groups, respectively, had VNTs ? 0·5 IU/mL, considered an adequate response by the WHO. After two 1 or 2 ?g doses all recipients had titers ? 0.5 IU/mL by Day 43. Day 57 GMTs were not significantly lower than those with Rabipur, which elicited adequate responses in all vaccinees after two doses. CV7202-elicited VNT were significantly correlated with RABV-G-specific IgG antibodies (r² = 0.8319, p < 0.0001).

Conclusions

Two 1 ?g or 2 ?g doses of CV7202 were well tolerated and elicited rabies neutralizing antibody responses that met WHO criteria in all recipients, but 5 ?g had unacceptable reactogenicity for a prophylactic vaccine. ClinicalTrials.gov Identifier: NCT03713086.

SUBMITTER: Aldrich C

PROVIDER: S-EPMC7825876 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Proof-of-concept of a low-dose unmodified mRNA-based rabies vaccine formulated with lipid nanoparticles in human volunteers: A phase 1 trial.

Aldrich Cassandra C Leroux-Roels Isabel I Huang Katell Bidet KB Bica Mihai Alexandru MA Loeliger Edde E Schoenborn-Kellenberger Oliver O Walz Lisa L Leroux-Roels Geert G von Sonnenburg Frank F Oostvogels Lidia L

Vaccine 20210122 8

<h4>Introduction</h4>In a first-in-human study immune responses to rabies virus glycoprotein (RABV-G)-mRNA vaccine were dependent on the route of administration, necessitating specialized devices. Following successful preclinical studies with mRNA encapsulated in lipid nanoparticles (LNP), we tested an mRNA-LNP formulation (CV7202).<h4>Methods</h4>In this phase 1, multi-center, controlled study in Belgium and Germany we enrolled 55 healthy 18-40-year-olds to receive intramuscular injections of 5 ...[more]

PMID: 33487468

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Dataset Information

Proof-of-concept of a low-dose unmodified mRNA-based rabies vaccine formulated with lipid nanoparticles in human volunteers: A phase 1 trial.

Introduction

Methods

Results

Conclusions

Publications

Proof-of-concept of a low-dose unmodified mRNA-based rabies vaccine formulated with lipid nanoparticles in human volunteers: A phase 1 trial.

Similar Datasets

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