Background

COVID-19 and influenza are both highly contagious respiratory diseases with a wide range of severe symptoms and cause great disease burdens globally. It has become very urgent and important to develop a bivalent vaccine that is able to target these two infectious diseases simultaneously. 

SARS-CoV-2 belongs to a betacoronavirus subfamily that includes enveloped, large and positive-stranded RNA viruses responsible for causing severe respiratory system, gastrointestinal and neurological symptoms. The key determinant for the infectivity of SARS-CoV-2 depends on the host specificity with the viral surface-located trimeric spike glycoprotein (SP), which is commonly cleaved by host proteases into an N-terminal S1 subunit and a membrane-embedded C-terminal S2 region. The Delta variant is the most contagious of all the known SARS-CoV-2 variants. Some research suggests that it’s more than twice as transmissible as the original SARS-CoV2 strain. The rapid spread of the highly transmissible SARS-CoV-2 Delta variant, and its ability to infect immunized people, necessitates the development of a vaccine that specifically targets the Delta strain and related variants. 

Vesicular stomatitis virus (VSV) is a single-stranded negative-sense RNA virus belong in the family Rhabdoviridae. Although VSV can cause illness in livestock and some animals, it is highly restricted to cause disease in humans by the human IFN response and generally does not cause any or only very mild symptoms. The VSV platform may be used to generate glycoprotein vaccines and is considered safe and highly immunogenic.

Influenza virus disease is another contagious respiratory illness. Influenza virus has four types including Influenza A, B, C and D among which influenza A and B are of economic and medical importance to humans. It should be noticed that the reduced numbers of influenza virus infection experienced currently is due to the availability of the vaccination each year, however, there are some issues regarding the production of vaccine based on predictions which may not always be clear match with influenza infection in circulation in a given year. Also, this effort has not successfully eradicated the influenza virus infection. Therefore, it is also urgent to develop a universal vaccine that must be used to elicit immune responses that can prevent or attenuate the infection of different strains of influenza virus.

Up to now, there are several licensed vaccines have been successfully developed for COVID-19 and influenza infection. However, each of the prepared vaccines can only target either SARS-CoV2 or influenza, so, it is necessary to develop an universal vaccine which can simultaneously against both SARS-CoV2 and influenza viruses. 

Technology Overview

Researchers at the University of Manitoba have developed an attenuated replicating recombinant Vesicular Stomatitis Virus (VSV)-based dual-Action Vaccine that is able to express both the SARS-CoV2 Spike glycoprotein (SP) or its component(s) and an influenza M2 ectodomain (M2e) which is fused with a DC-targeting/activation domain (EboGPΔM), derived from a Zaire Ebola glycoprotein. 

The expression of SARS-CoV-2 Delta variant spike protein (SP) or RBD and influenza M2 ectodomains of these bivalent vaccine candidates and their abilities to induce immune responses against SARS-CoV-2 SP, especially Delta SP, and influenza M2e were characterized. 

Immunization with these bivalent rVSV vaccines induced:

1) Efficient humoral and cell-mediated immune responses against both SARS-CoV-2 and influenza M2e protein; 

2) High levels of neutralizing antibodies that protected cells against SARS-CoV-2 Delta and other SP-pseudovirus infections in cell culture; 

3) Efficiently protected hamsters/mice from SARS-CoV-2 Delta infection and the lethal challenge of H1N1 and H3N2 influenza viruses. 

Overall, this technology and supportive animal studies provides convincing evidence for the high efficacy of the bivalent vaccine to prevent SARS-CoV-2 Delta variants and influenza infections. 

Benefits

• Efficient humoral and cell-mediated immune responses against both SARS-CoV-2 and influenza M2e protein. 
• High levels of neutralizing antibodies that protected cells against SARS-CoV-2 Delta and other SP-pseudovirus infections in cell culture. 
• Demonstrated efficient protection in hamsters and mice from SARS-CoV-2 Delta infection and the lethal challenge of H1N1 and H3N2 influenza viruses. 
• Intermuscular and internasal immunization both induced efficient anti-SARS-CoV2 RBD and anti-M2 immune responses in mice.
• The V-EboGPΔM-based multivalent vaccine platform is versatile because the V-EboGPΔM can be used a vector to express heterologous polypeptide antigens and/or epitopes of pathogens; and can be adapted for development of vaccines against other pathogens during future pandemic outbreaks.
• The replication VSV vaccine platform provides safe, easy, and scalable production.

Applications

• A multivalent vaccine that effectively protects against both COVID-19 and influenza.
• Rapid and robust immune response after a single immunization, making public health vaccination campaigns much more effective.