TMV-083 / Institut Pasteur, Merck (MSD), University of Pittsburgh - LARVOL DELTA

Rapid bioreactor process optimization and scale-up for production of a measles vector COVID-19 vaccine candidate. (PubMed, Biotechnol Prog) - "These rapid process option evaluations were conducted parallel to critical path scale up, and the combined efforts enabled the rapid demonstration of two full manufacturing scale 2000 L bioreactors less than 6 months after virus seed delivery, culminating in the first large scale measles production process capable of addressing the high dose demands of a pandemic response scenario. Despite subsequent clinical discontinuation of the V591 vaccine candidate, the findings described herein will be useful for enabling rapid and scalable production of other measles-vectored vaccine candidates, oncolytic measles strains, or cell and gene therapies."

Journal • Gene Therapies • Infectious Disease • Measles • Novel Coronavirus Disease • Respiratory Diseases

How to accelerate the supply of vaccines to all populations worldwide? Part III: Reflections after the pandemic. (PubMed, Vaccine) - "When the Covid-19 pandemic was declared by WHO, a team of vaccine manufacturers worked with the COVAX (COVID-19 Vaccine Global Access) Manufacturing SWAT (Support Work to Advance) team to propose regulatory agilities for accelerating access to vaccines...Flexibility and reliance are still needed to ensure timely product availability. This article emphasizes the importance of continuing pandemic preparedness and acting on lessons learned."

Journal • Infectious Disease • Novel Coronavirus Disease

A 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. (PubMed, J Virol) - "Here, we evaluate a measles virus (MV)-vectored vaccine expressing a stabilized prefusion SARS-CoV-2 spike (S) protein (MV-ATU3-S2PΔF2A; V591) with demonstrated immunogenicity in mouse models (see companion article [J...This study uses a safe and effective measles vaccine as a platform for vaccination against SARS-CoV-2...After challenge, these AGMs produced less virus in mucosal secretions, for a shorter period, and had a reduced disease burden in the lungs compared to control animals. At necropsy, lower levels of viral RNA were detected in tissue samples from vaccinated animals, and the lungs of these animals lacked the histologic hallmarks of SARS-CoV-2 disease observed exclusively in the control AGMs."

Journal • P1/2 data • Gastrointestinal Disorder • Infectious Disease • Measles • Novel Coronavirus Disease • Respiratory Diseases

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. (PubMed, J Virol) - "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. These unique in-human trials of a measles vector-based COVID-19 vaccine revealed insufficient immunogenicity, which may be the consequence of previous exposure to the pediatric measles vaccine. The three studies together in mice, primates, and humans provide a unique insight into the measles-vectored vaccine platform, raising potential limitations of surrogate preclinical models and calling for further refinement of the platform."

Journal • P1/2 data • Preclinical • Infectious Disease • Measles • Novel Coronavirus Disease • Pediatrics • Respiratory Diseases

The Future of Epidemic and Pandemic Vaccines to Serve Global Public Health Needs. (PubMed, Vaccines (Basel)) - "This will only happen if we question all prior assumptions and learn the lessons offered by the current pandemic. We invite submissions to the special issue, which we hope will help guide the world towards a global vaccine research, development, and manufacturing ecosystem that better balances and integrates scientific, clinical trial, regulatory, and commercial interests and puts global public health needs first."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Recombinant measles virus expressing prefusion spike protein stabilized by six rather than two prolines is more efficacious against SARS-CoV-2 infection. (PubMed, J Med Virol) - "In addition, hamsters immunized with rMeV-preS-6P were completely protected from the challenge with a Delta variant of SARS-CoV-2. Our results demonstrate that rMeV-preS-6P is significantly more efficacious than rMeV-preS-2P, highlighting the value of using preS-6P as the antigen for developing vaccines against SARS-CoV-2."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IFNAR1

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. (PubMed, EBioMedicine) - P1 | "While V591 was generally well tolerated, the immunogenicity was not sufficient to support further development."

Clinical • Journal • P1 data • Chikungunya • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Safety and immunogenicity of the measles vector-based SARS-CoV-2 vaccine candidate, V591, in adults: results from a phase 1/2 randomised, double-blind, placebo-controlled, dose-ranging trial. (PubMed, EBioMedicine) - P1/2 | "V591 was generally well tolerated, but immunogenicity was insufficient to warrant continued development."

Clinical • Journal • P1/2 data • Fatigue • Infectious Disease • Musculoskeletal Pain • Novel Coronavirus Disease • Pain • Respiratory Diseases

Use of Stability Modeling to Support Accelerated Vaccine Development and Supply. (PubMed, Vaccines (Basel)) - "It is demonstrated that modeling methodologies need to be tailored to the nature of the vaccine, the available prior knowledge, and the monitored attributes. Considering that the well-established strategies reported in ICH or WHO guidelines are not always broadly applicable to vaccines, this article represents an important source of information for vaccine researchers and manufacturers, setting the grounds for further discussion within the vaccine industry and with regulators."

Journal

COVID-19-101: Clinical Trial to Evaluate the Safety and Immunogenicity of the COVID-19 Vaccine (clinicaltrials.gov) - P1; N=90; Completed; Sponsor: Institut Pasteur; Active, not recruiting ➔ Completed

Clinical • Trial completion • Infectious Disease • Novel Coronavirus Disease

Merck Discontinues Development of SARS-CoV-2/COVID-19 Vaccine Candidates; Continues Development of Two Investigational Therapeutic Candidates (Businesswire) - P1, N=252; NCT04569786; P1/2, N=260; NCT04498247; Sponsor: Merck Sharp & Dohme Corp.; "Merck...announced that the company is discontinuing development of its SARS-CoV-2/COVID-19 vaccine candidates, V590 and V591, and plans to focus...on advancing two therapeutic candidates, MK-4482 and MK-7110. This decision follows Merck’s review of findings from Phase 1 clinical studies for the vaccines. In these studies, both V590 and V591 were generally well tolerated, but the immune responses were inferior...MK-7110 (formerly CD24Fc)...Full results from this study are expected in the first quarter of 2021....Molnupiravir is currently being evaluated in Phase 2/3 clinical trials in both the hospital and out-patient settings....The company anticipates initial efficacy data in the first quarter of 2021, which Merck plans to share publicly if clinically meaningful."

Discontinued • P1 data • P2/3 data • P3 data • Infectious Disease • Novel Coronavirus Disease

A Study to Assess Safety, Tolerability, and Immunogenicity of V591 (COVID-19 Vaccine) in Healthy Participants (V591-001) (clinicaltrials.gov) - P1/2; N=260; Not yet recruiting; Sponsor: Merck Sharp & Dohme Corp.; Phase classification: P1 ➔ P1/2

Clinical • Phase classification • Infectious Disease • Novel Coronavirus Disease

A Study to Assess Safety, Tolerability, and Immunogenicity of V591 (COVID-19 Vaccine) in Healthy Participants (V591-001) (clinicaltrials.gov) - P1/2; N=260; Active, not recruiting; Sponsor: Merck Sharp & Dohme Corp.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A Study to Assess Safety, Tolerability, and Immunogenicity of V591 (COVID-19 Vaccine) in Healthy Participants (V591-001) (clinicaltrials.gov) - P1; N=260; Not yet recruiting; Sponsor: Merck Sharp & Dohme Corp.

Clinical • New P1 trial • Infectious Disease • Novel Coronavirus Disease

Merck says early data from COVID-19 vaccines expected this year (Reuters) - "Merck & Co Inc on Tuesday said it expects to report results from early-stage studies of two potential COVID-19 vaccines before the end of the year and has advanced an experimental antiviral drug into late-stage testing....Initial data showing whether V591 triggers an immune response in trial participants is expected by the end of the year....The drugmaker is also collaborating with research non-profit IAVI on a second candidate....It is several weeks behind the V591 program but on a similar development track, Perlmutter said."

Clinical data • Infectious Disease • Novel Coronavirus Disease

A Study to Assess Safety, Tolerability, and Immunogenicity of V591 (COVID-19 Vaccine) in Healthy Participants (V591-001) (clinicaltrials.gov) - P1/2; N=260; Recruiting; Sponsor: Merck Sharp & Dohme Corp.; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Infectious Disease • Novel Coronavirus Disease

A Study to Assess Safety, Tolerability, and Immunogenicity of V591 (COVID-19 Vaccine) in Healthy Participants (V591-001) (clinicaltrials.gov) - P1/2; N=260; Active, not recruiting; Sponsor: Merck Sharp & Dohme Corp.; Trial completion date: Apr 2022 ➔ Mar 2021; Trial primary completion date: Apr 2022 ➔ Mar 2021

Clinical • Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Merck starts recruitment for COVID-19 vaccine trial (Financial Post) - "U.S. drugmaker Merck & Co Inc has begun recruiting participants to its early-stage COVID-19 vaccine study....The phase 1/2 trial, which is based in Belgium, aims to recruit 260 healthy participants to test the experimental vaccine V591..."

Enrollment status • Infectious Disease • Novel Coronavirus Disease

A Study to Assess Safety, Tolerability, and Immunogenicity of V591 (COVID-19 Vaccine) in Healthy Participants (V591-001) (clinicaltrials.gov) - P1/2; N=263; Terminated; Sponsor: Merck Sharp & Dohme Corp.; Active, not recruiting ➔ Terminated; The study was terminated based on an interim assessment of immunogenicity

Clinical • Trial termination • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

COVID-19-101: Clinical Trial to Evaluate the Safety and Immunogenicity of the COVID-19 Vaccine (clinicaltrials.gov) - P1; N=90; Active, not recruiting; Sponsor: Institut Pasteur; Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Novel Coronavirus Disease

COVID-19-101: Clinical Trial to Evaluate the Safety and Immunogenicitiy of the COVID-19 Vaccine (clinicaltrials.gov) - P1; N=90; Recruiting; Sponsor: Institut Pasteur; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Infectious Disease • Novel Coronavirus Disease

COVID-19-101: Clinical Trial to Evaluate the Safety and Immunogenicitiy of the COVID-19 Vaccine (clinicaltrials.gov) - P1; N=90; Not yet recruiting; Sponsor: Institut Pasteur

Clinical • New P1 trial • Infectious Disease • Novel Coronavirus Disease

[VIRTUAL] Detection of SARS-CoV-2 by the first (RUO) commercial rapid multiplex PCR respiratory panel (ECCMID 2020) - "Background: Since the first cases of severe acute respiratory infections associated with SARS-CoV-2 (former 2019-nCoV) in China, more than 60 000 cases have been reported... The RUO-version of QIA-RP-nCoV assay allows sensitive, specific and rapid, about one hour on demand vs four hours for the WHO method, detection of SARS-CoV-2 coupled with detection of all clinically relevant respiratory viruses. Our results are in line with the limit of detection provided by the manufacturer at 300 copies/mL. The analyzer and cartridge design allow its use in any laboratory, even not PCR-trained, but also permit point-of-care testing by direct use of the nasopharyngeal swab without further manipulation."

Infectious Disease • Novel Coronavirus Disease

SEN-CoV-Fadj: Efficacy and Safety Evaluation of Treatment Regimens in Adult COVID-19 Patients in Senegal (clinicaltrials.gov) - P3; N=258; Not yet recruiting; Sponsor: Institut Pasteur de Dakar

Clinical • New P3 trial • Novel Coronavirus Disease

COVIDAXIS: Chemoprophylaxis of SARS-CoV-2 Infection (COVID-19) in Exposed Healthcare Workers (clinicaltrials.gov) - P3; N=1200; Active, not recruiting; Sponsor: Centre Hospitalier Universitaire de Saint Etienne; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Infectious Disease • Novel Coronavirus Disease • PCR