Researchers develop a multivalent vaccine for COVID-19 and influenza

Researchers at Duke University, USA, are looking into the possibility of a combined influenza & coronavirus disease 2019 (COVID-19) vaccine that could be used to simultaneously protect against annual flu strains and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Preclinical results showed the vaccine protected mice from both SARS-CoV-2 and the flu.

The vaccine could be a cost-effective measure in preventing influenza and coronavirus infections in countries that cannot afford expensive vaccine production.

The influenza-based, multi-valent vaccines may represent a generalizable approach to reduce the time and manufacturing requirements for the development of novel vaccines. Since the current influenza vaccine is composed of three or four distinct strains, this approach could be even more highly multiplexed than eliciting responses against two pathogens,” wrote the researchers.

The study “Influenza viral particles harboring the SARS-CoV-2 spike RBD as a combination respiratory disease vaccine” is available as a preprint on the bioRxiv* server, while the article undergoes peer review.

Study: Influenza viral particles harboring the SARS-CoV-2 spike RBD as a combination respiratory disease vaccine. Image Credit: Numstocker / Shutterstock

Seasonal combination vaccine elicits antibody responses for both viruses

The researchers crafted a recombinant influenza A virus (IAV) genetic platform that allows the influenza virus to act as a vector packaging the SARS-CoV-2 spike protein. The goal of the seasonal combination vaccine is to target both influenza viruses and SARS-CoV-2.

To test the vaccine’s effectiveness, they primed naive mice with either a wild-type strain or the combination vaccine. After three weeks, the animals were given an intramuscular booster shot of the inactivated vaccine or a control shot. The researchers collected blood samples two weeks after the booster to evaluate antibody activity.

High serum IgG levels were observed in vaccinated mice when blood samples were exposed to either the IAV hemagglutinin (HA) protein or the SARS-CoV-2 receptor-binding domain (RBD) protein. There was also no difference between IgG reactivity between both vaccine groups — even when there was less of the IAV HA protein in the vaccine.

High antibody binding activity was associated with high neutralizing activity against the H1N1 IAV.

The serum samples from vaccinated mice displayed stronger antibody reactivity against the SARS-CoV-2 receptor binding domain than the mice given the wild-type IAV vaccine. In addition, mice given the combination vaccine showed more neutralizing activity than those given the wild-type IAV vaccine group.

Thus, the combination viral IAV/SARS CoV-2 vaccine is immunogenic and elicits a potentially protective humoral response against SARS-CoV-2. This additional antigenicity comes at no apparent cost for IAV directed immune responses, validating the platform concept of a combination viral particle-based vaccine,” concluded the researchers.

Combination vaccine protects against the flu and severe COVID-19 disease

The researchers looked at how the vaccine fares up against lethal viral doses — enough that would produce severe disease.

They infected C57BL/6 mice and gave them the vaccine or a control. Results showed the mice in the control group rapidly lost weight and died. However, mice that received the wild-type IAV and the recombinant IAV/SARS-CoV-2 vaccine did not experience weight loss and did not succumb to infection.

The experiment was repeated with transgenic mice that expressed the human SARS-CoV-2 receptor — increasing susceptibility for severe disease from the wildtype SARS-CoV-2 strain. Two weeks after receiving a booster shot, they were given an intranasal lethal dose of SARS-CoV-2.

Mice vaccinated with the wild-type IAV experienced weight loss and death. In contrast, the mice with the combination vaccine were protected from infection. The researchers suggest the lack of infection in mice with the combination vaccine is likely due to the production of neutralizing antibodies.

Future Work

Creating a combination vaccine to combat the influenza virus and SARS-CoV-2 would help ramp up production by reducing the time and manufacturing costs for vaccine development.

Though the researchers note several questions need to be addressed before implementing this vaccine in humans. Future work will need to test whether the receptor-binding domain (RBD) component of the spike protein is the most appropriate antigen or if the full spike protein would be more effective.

Additionally, genetic engineering of the virus reduces viral yield, and future studies will need to evaluate how significant this production would be for vaccine manufacturing. Studies using different influenza viruses or HA proteins are also required to see whether the vaccine can use different influenza strains that can appropriately incorporate the SARS-CoV-2 receptor binding domain.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Jocelyn Solis-Moreira

Jocelyn Solis-Moreira graduated with a Bachelor's in Integrative Neuroscience, where she then pursued graduate research looking at the long-term effects of adolescent binge drinking on the brain's neurochemistry in adulthood.