NPJ Vaccines . M2e nanovaccines supplemented with recombinant hemagglutinin protect chickens against heterologous HPAI H5N1 challenge

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NPJ Vaccines


. 2024 Sep 5;9(1):161.
doi: 10.1038/s41541-024-00944-7. M2e nanovaccines supplemented with recombinant hemagglutinin protect chickens against heterologous HPAI H5N1 challenge

Cynthia Calzas ¹ , Tamiru N Alkie ² , Matthew Suderman ³ , Carissa Embury-Hyatt ² , Vinay Khatri ^{4 5} , Ronan Le Goffic ¹ , Yohannes Berhane ^{2 6 7} , Steve Bourgault ⁴ , Denis Archambault ⁸ , Christophe Chevalier ⁹



Affiliations

• PMID: 39237609
• DOI: 10.1038/s41541-024-00944-7

Abstract

Current poultry vaccines against influenza A viruses target the globular head region of the hemagglutinin (HA1), providing limited protection against antigenically divergent strains. Experimental subunit vaccines based on the conserved ectodomain of the matrix protein 2 (M2e) induce cross-reactive antibody responses, but fail to fully prevent virus shedding after low pathogenic avian influenza (LPAI) virus challenge, and are ineffective against highly pathogenic avian influenza (HPAI) viruses. This study assessed the benefits of combining nanoparticles bearing three tandem M2e repeats (NR-3M2e nanorings or NF-3M2e nanofilaments) with an HA1 subunit vaccine in protecting chickens against a heterologous HPAI H5N1 virus challenge. Chickens vaccinated with the combined formulations developed M2e and HA1-specific antibodies, were fully protected from clinical disease and mortality, and showed no histopathological lesions or virus shedding, unlike those given only HA1, NR-3M2e, or NF-3M2e. Thus, the combined vaccine formulations provided complete cross-protection against HPAI H5N1 virus, and prevented environmental virus shedding, crucial for controlling avian influenza outbreaks.

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A first in the fight against the H5N1 avian influenza virus


Denis Archambault co-signs a study in the prestigious journal NPJ Vaccines – Nature .

By Marie-Claude Bourdon

September 9, 2024 at 10:11 a.m.

Professor Denis Archambault of the Department of Biological Sciences co-authored with Christophe Chevalier, research director at the National Institute for Agricultural, Food and Environmental Research (INRAE) in France, a study published on September 5 in the prestigious journal NPJ Vaccines – Nature . The study, conducted by collaborators from different laboratories in Canada and France, focuses on a new vaccine preparation against avian influenza A H5N1 designed by the team using nanoparticles. Its results show that chickens immunized with this preparation were 100% protected, without clinical signs of the disease, without viral shedding and without pathological lesions, in the context of an experimental infection. This is a first in the fight against this highly contagious disease.

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Sterilizing immunity

According to Denis Archambault, such results demonstrate "sterilizing" immunity. "We say that immunity is sterilizing when viral transmission from one individual to another is completely annihilated, given the absence of viral excretion," explains the researcher. This advantage is crucial for preventing epidemics.

“What is even more important is that these results were obtained during experiments conducted in a heterologous infection system,” notes Denis Archambault. In other words, the strain of H5N1 used to infect the chickens was very far, phylogenetically, from the one used to prepare part of the vaccine material, in this case a protein called HA (hemagglutinin) located on the surface of the viruses. “The uniqueness of our approach lies in this high degree of divergence,” emphasizes the researcher. “This implies that the vaccine formulation developed by our team can be considered a so-called “universal” vaccine and counter any variant of the H5N1 influenza virus.”

"...the vaccine formulation developed by our team can be considered a so-called "universal" vaccine and counter any variant of the H5N1 influenza virus"
Denis Archambault

Professor in the Department of Biological Sciences

This vaccine preparation incorporates nanoparticles containing an amino acid sequence conserved between viral strains, called M2e, in addition to a recombinant protein, namely the globular HA1 part of the HA protein. The combination of these elements proved to be significantly more effective than when they were inoculated separately.

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A widely spread virus

The H5N1 virus is present in many parts of the world, including Asia, South America, Europe, the United States and Canada. This virus causes a high number of deaths in the poultry industry, with mortality rates ranging from 95 to 100% in a very short period of time. In France, avian flu is causing disastrous losses among duck farmers for foie gras production. Even though ducks are, like most wild birds, asymptomatic, they spread the virus into the environment and must be slaughtered preventively. In the spring of 2022, the Quebec company Canards du Lac Brome also had to euthanize some 150,000 ducks to prevent the spread of the virus.

H5N1 has also been detected in marine mammals such as seals and walruses, and, more worryingly, in domestic animals such as dogs. In April, cases were reported in the United States in cows and cats.

These different cases suggest that avian flu is increasingly adapting to mammals. "The H5N1 virus and its like may represent one of the greatest threats to humans since the Spanish flu of 1918," says Denis Archambault. It is worth noting that case fatality rates of 52 to 62% have been reported in humans exposed to the virus." In comparison, estimates of the case fatality rate for COVID-19, before the introduction of vaccines, varied between 0.5 and 1%.

"The H5N1 virus and its like pose possibly one of the greatest threats to humans since the Spanish flu of 1918."

Fortunately, human infection with avian influenza remains rare. Until now, it has been limited to people who work in agricultural settings or who have been in contact with infected poultry or livestock. However, last week, an infection was reported in an American man who had no known exposure to infected animals or birds. This case, which is still under investigation by Missouri state health officials, raises concerns about possible community spread.

Could human-to-human transmission of the H5N1 virus become a reality? According to Denis Archambault and several other scientists, the question is not if it will happen, but when. "Our discovery is of capital importance because it provides a cutting-edge vaccine tool to combat this potential scourge," says the professor.

Denis Archambault grew up on a dairy farm and worked as a veterinarian for a few years before completing a doctorate in microbiology and immunology and devoting himself to research. “The efforts to combat this avian flu virus are particularly close to my heart,” says the researcher.

This research, led by Denis Archambault as principal investigator, was carried out thanks to major grants from the International Development Research Centre (IDRC) and the Bill & Melinda Gates Foundation. The results have been the subject of a patent application and several potential pharmaceutical partners in Europe, the United States and Canada have already expressed interest in this discovery in the context of use not only in animals, but also in humans.

Other researchers, including Steve Bourgault, professor in the Department of Chemistry, Ronan Le Goffic, from INRAE, and Yohannes Berhane, head of the Canadian influenza reference laboratory at the National Centre for Foreign Animal Diseases (NCFAD) in Winnipeg, collaborated on this study.

https://actualites.uqam.ca/2024/une-...-aviaire-h5n1/