COVID-19: progress update on the Institut Pasteur's scientific response and vaccine candidate research programs

Press release

Since early 2020, the Institut Pasteur has been engaged in research in several of its areas of scientific expertise, including virology, diagnostics, pathophysiology, epidemiology, modeling, therapeutic research and vaccine research. A number of research programs to find a vaccine for SARS-CoV-2, the virus responsible for the COVID-19 epidemic, are under way. In light of the intermediate results of its Phase I clinical trial, the Institut Pasteur is stopping development of one of its vaccine candidates, the vaccine based on the measles vaccine virus. The Institut Pasteur will continue to pursue the development of other vaccine candidates which have reached preclinical phase, alongside its concerted scientific efforts to tackle the COVID-19 epidemic.

The decision not to pursue the development of the vaccine candidate based on the measles vaccine virus was made following an analysis of the intermediate results obtained from Phase I trials, which began in August 2020. The decision was taken in parallel with the decision by the Merck Group (known as MSD outside the United States and Canada), the industry partner for this research. In these trials involving the first administration to humans, the vaccine candidate was well tolerated, but the immune responses induced by the vaccine were inferior to both those observed in individuals who had recovered from natural infection and those observed with the vaccines currently authorized for SARS-CoV-2/COVID-19.

The Institut Pasteur would like to thank all the people and organizations that have contributed to the research carried out on this vaccine candidate over the past year, especially all the volunteers who have participated and are continuing to participate in clinical trials. It would also like to thank CEPI (the Coalition for Epidemic Preparedness Innovations), which funded the first stages of research and development.

This decision in no way affects the Institut Pasteur's continued research on two other vaccine candidates based on different methodologies. The first, administered by nasal route, is being developed with the biotech company TheraVectys, an Institut Pasteur spin-off specializing in vaccine development. The second is a DNA vaccine candidate. These two candidates are currently in preclinical phase.

The decision also has no adverse impact on the continuation of other vaccine research projects being conducted in partnership with Themis/Merck-MSD, based on the use of the measles vaccine virus as a vaccine vector and aimed at other infectious diseases (Lassa fever and chikungunya).

The Institut Pasteur's teams are currently pursuing their large-scale response to the COVID-19 epidemic. In 2020, the Institut Pasteur launched nearly a hundred research programs, involving more than 450 scientists (a quarter of its research staff) in 69 research units (half of its resources) and leading to nearly a hundred scientific publications. This research is centered on several of the Institut Pasteur's areas of scientific expertise, including virology, diagnostics, pathophysiology, epidemiology, modeling, therapeutic research and vaccine research. As we enter a worrying new phase of the pandemic following the emergence of several viral variants, this strong, collective, interdisciplinary response will be further stepped up in 2021.


About the recombinant vaccine using the "measles vector"

The virus used in the measles vaccine is used here as a vector for the development of recombinant vaccines expressing antigens from other pathogens (antigen fragments from dengue, Lassa fever or other viruses responsible for emerging diseases). In this case, the antigen expressed is the spike protein antigen from the SARS-CoV-2 virus. The spike protein, the "entry key" that allows the virus into cells, forms spikes on the surface of the viral envelope.
This methodology using the measles vector has also been implemented in recent years for the development of other vaccine candidates. A chikungunya vaccine candidate has obtained positive results in Phase I and II trials, as published in The Lancet, paving the way for a Phase III trial. Vaccine candidates for the Lassa fever and Zika viruses are also in development.

A Phase I clinical trial in humans began in August 2020 at two centers in France and Belgium. The aim of this trial was to test the safety and efficacy (immunogenicity) of the vaccine candidate. A total of 90 healthy volunteers took part in the study. They received two doses of the vaccine candidate and/or a placebo. The two injections were administered 28 days apart, the time needed to enable the immune system to identify and respond to the presence of the antigen. The majority of the volunteers were assessed on a double-blind basis, meaning that neither the doctors nor the volunteers themselves knew whether they had been given the vaccine candidate or the placebo. This Phase I trial, sponsored by the Institut Pasteur, was conducted in France at the Cochin-Pasteur Clinical Investigation Center (CIC) in Cochin Hospital (Paris Public Hospital Network – AP-HP).
Development of the vaccine candidate was launched in partnership with the Austrian biotech company Themis and with the support of CEPI. Themis was acquired in May 2020 by the pharmaceutical group Merck (known as MSD in Europe), one of the top four vaccine companies in the world.

About the other two vaccine candidates for which the Institut Pasteur is continuing development

These two programs are currently at the end of the preclinical research phase, the stage before testing in humans.

Vaccine candidate based on the use of a lentiviral vector

This vaccine candidate, administered by nasal route, is being developed with the biotech company TheraVectys, an Institut Pasteur spin-off. It is based on the use of a lentiviral vector which is harmless for humans. The aim is to induce a specific immune response to the spike protein, triggering the production of both antibodies capable of recognizing the SARS-CoV-2 virus and cytotoxic cells capable of destroying infected cells and thereby preventing infection from developing.
The theory is that an effective SARS-CoV-2 vaccine will have to induce vaccine protection at the site at which the virus enters the body, namely the respiratory tract; it is thought that neutralizing antibodies present in the blood only contribute minimally to protection.
Based on the first positive results obtained with this lentiviral vector vaccine candidate for SARS-CoV-2, TheraVectys is keen to set up a first clinical trial.

DNA vaccine candidate

This type of vaccine candidate is based on the principle of injecting a DNA fragment into human cells. The cells recognize the DNA fragment and transcribe it into messenger RNA that is capable of inducing production of the SARS-CoV-2 virus spike protein, thereby turning human cells into temporary "factories" for spike protein production. The immune system then recognizes these proteins and produces antibodies to neutralize them, and the presence of these antibodies is likely to prevent any subsequent infection with SARS-CoV-2. This vaccine approach has obtained promising results in tests on animal models, paving the way for the transition to clinical trials in humans.


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