The large global burden of viral infections and especially the rapidly spreading vector-borne diseases and other emerging viral diseases show the need for new approaches in vaccine development. Several new vaccine technology platforms have been developed and are under evaluation. Areas covered: This article discusses the measles vector platform technology derived from the safe and highly efficacious measles virus vaccine. The pipeline of measles-vectored vaccine candidates against viral diseases is reviewed. Particular focus is given to the Chikungunya vaccine candidate as the first measles-vectored vaccine that demonstrated safety, immunogenicity, and functionality of the technology in humans even in the presence of pre-existing anti-measles immunity and thus achieved proof of concept for the technology. Expert commentary: Demonstrating no impact of pre-existing anti-measles immunity in humans on the response to the transgene was fundamental for the technology and indicates that the technology is suitable for large-scale immunization in measles pre-immune populations. The proof of concept in humans combined with a large preclinical track record of safety, immunogenicity, and efficacy for a variety of pathogens suggest the measles vector platform as promising plug-and-play vaccine platform technology for rapid development of effective preventive vaccines against viral and other infectious diseases.
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| http://dx.doi.org/10.1080/14760584.2019.1562908 | DOI Listing |
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A measles-vectored vaccine candidate expressing prefusion-stabilized SARS-CoV-2 spike protein brought to phase I/II clinical trials: candidate selection in a preclinical murine model.
J Virol
May 2024
Institut Pasteur, Université Paris Cité, Département de Santé Globale, Paris, France.
In the early COVID-19 pandemic with urgent need for countermeasures, we aimed at developing a replicating viral vaccine using the highly efficacious measles vaccine as vector, a promising technology with prior clinical proof of concept. Building on our successful pre-clinical development of a measles virus (MV)-based vaccine candidate against the related SARS-CoV, we evaluated several recombinant MV expressing codon-optimized SARS-CoV-2 spike glycoprotein. Candidate V591 expressing a prefusion-stabilized spike through introduction of two proline residues in HR1 hinge loop, together with deleted S1/S2 furin cleavage site and additional inactivation of the endoplasmic reticulum retrieval signal, was the most potent in eliciting neutralizing antibodies in mice.
View Article and Find Full Text PDFA measles-vectored vaccine candidate expressing prefusion-stabilized SARS-CoV-2 spike protein brought to phase I/II clinical trials: protection of African green monkeys from COVID-19 disease.
J Virol
May 2024
Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Article Synopsis
- SARS-CoV-2, which emerged in late 2019, has caused a global pandemic, with 34 vaccines approved and about 67% of the world vaccinated, yet new infections and variants still pose challenges.
- Researchers evaluated a new measles virus-vectored vaccine (V591) designed to target the SARS-CoV-2 spike protein in an African green monkey model, demonstrating strong immune responses pre-challenge.
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Surface-modified measles vaccines encoding oligomeric, prefusion-stabilized SARS-CoV-2 spike glycoproteins boost neutralizing antibody responses to Omicron and historical variants, independent of measles seropositivity.
mBio
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Department of Molecular Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Serum titers of SARS-CoV-2-neutralizing antibodies (nAbs) correlate well with protection from symptomatic COVID-19 but decay rapidly in the months following vaccination or infection. In contrast, measles-protective nAb titers are lifelong after measles vaccination, possibly due to persistence of the live-attenuated virus in lymphoid tissues. We, therefore, sought to generate a live recombinant measles vaccine capable of driving high SARS-CoV-2 nAb responses.
View Article and Find Full Text PDFImmunogenicity, safety, and tolerability of a recombinant measles-vectored Lassa fever vaccine: a randomised, placebo-controlled, first-in-human trial.
Lancet
April 2023
Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, Lyon, France; Centre International de Recherche en Infectiologie, Université de Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.
Background: Lassa fever is a substantial health burden in west Africa. We evaluated the safety, tolerability, and immunogenicity of a recombinant, live-attenuated, measles-vectored Lassa fever vaccine candidate (MV-LASV).
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Safety and immunogenicity of a measles-vectored SARS-CoV-2 vaccine candidate, V591 / TMV-083, in healthy adults: results of a randomized, placebo-controlled Phase I study.
EBioMedicine
January 2022
Institut Pasteur, Université de Paris, Innovation Office, Vaccine Programs, Paris, France. Electronic address:
Background: V591 (TMV-083) is a live recombinant measles vector-based vaccine candidate expressing a pre-fusion stabilized SARS-CoV-2 spike protein.
Methods: We performed a randomized, placebo-controlled Phase I trial with an unblinded dose escalation and a double-blind treatment phase at 2 sites in France and Belgium to evaluate the safety and immunogenicity of V591. Ninety healthy SARS-CoV-2 sero-negative adults (18-55 years of age) were randomized into 3 cohorts, each comprising 24 vaccinees and 6 placebo recipients.
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