Measles-based vector vaccine protects mice against influenza A (H7N9) virus
A vaccine virus and a vector in one: The measles vaccine virus as a vector vaccine.
Researchers of the German Center for Infection Research (DZIF) at the Paul-Ehrlich-Institut (PEI) and Philipps-Universität Marburg used the "recombinant measles virus" vaccine platform to test vaccine candidates against the dangerous avian H7N9 influenza virus in an animal model. Vectored vaccines with a genetic blueprint of the viral surface proteins haemagglutinin (H7) or neuraminidase (N9) each induced specific antibodies in mice that could effectively inhibit H7N9 influenza viruses. H7-specific T cells were still detected in the animals two years after vaccination. Vaccination against H7 completely protected the mice against disease after infection. Vaccination against N9 mostly provided protection against a severe disease course.
The avian H7N9 influenza virus was discovered in China in 2013. Since then, there have been more than 1,500 confirmed infected patients, 39 percent of which have died. The transmission is predominantly zoonotic from animal to human and rarely occurs from human to human. However, some adaptation of the virus to mammals has already been observed in ferrets. Effective and safe vaccines are needed to be prepared for potential pandemics.
The COVID-19 pandemic has shown that vaccine platform technologies allow for rapid adjustments of vaccines for protection against other viruses. This study used the "recombinant measles virus (MV)" platform, in which vaccine strain-derived measles viruses were used as a vector (transport vehicle) for the transmission of genes encoding the surface proteins haemagglutinin (H7) or neuraminidase (N9) of the H7N9 influenza virus.
„We used recombinant vaccine strain-derived measles viruses against the H7N9 influenza virus in the mouse model. It turned out that using the relatively conserved neuraminidase as an antigen provides almost the same high level of protection as the highly variable haemagglutinin. We also found an astonishing longevity of T-cell responses against haemagglutinin.“
The two model vaccines that were developed, MVvac2-H7 (P) and MVvac2-N9 (P), were tested on mice. The mice were vaccinated twice every four weeks and developed high antibody titres. Vaccination against N9 failed in one mouse.
The antibodies formed not only bound to the H7N9 glycoproteins, but also prevented the haemagglutinin from binding to its receptor and the neuraminidase from being enzymatically active, which hinders the release of new virus particles. In consequence, the influenza virus is inactivated and prevented from causing disease.
In addition to the antibody response, H7-specific T cells were also detected in the H7-vaccinated mice.
Efficacy of H7 and N9 vaccination protection
Three weeks after the second vaccination, some mice were infected with the H7N9 influenza virus. While the control mice became so seriously ill that all had to be euthanised, the vaccinated mice survived except for one, which had been vaccinated with the N9 vaccine. The H7-vaccinated mice showed no signs of disease and they steadily gained weight over the course of the experiment. All but one of the N9-vaccinated mice fully recovered within four days after a slight initial weight loss.
Long-lasting cellular immunity after H7 vaccination
After two years, out of seven initially vaccinated mice per vaccine, three H7-vaccinated mice and two N9-vaccinated mice were still alive close to the end of their natural lifespan. Antigen-specific T-cell responses could be provoked in the H7 mice but not in the two N9 vaccinated animals. This is an indication of the longevity of this immune response.
The animal study shows that vaccines using the relatively conserved enzyme neuraminidase as an antigen in influenza viruses can protect against influenza almost as well as vaccines using the highly variable haemagglutinin antigen. The astonishing longevity of the T-cell response against haemagglutinin will be the subject of future research.
Source: Press release of the Paul-Ehrlich-Institut
Short summary of results by Dr Mühlebach as audio file: https://multimedia.gsb.bund.de/PEI/Audio/muehlebach-h7n9-quote.mp3
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