Researchers have claimed that they successfully immunised some animals against all 20 known influenza A and B virus strains, a significant progress toward the development of a universal flu vaccine. A universal flu vaccine that could protect people from a wide array of influenza virus strains is important because scientists cannot currently predict which subtype of influenza virus will cause the next pandemic. Most of the efforts of researchers to develop a universal flu vaccine have focused on a limited set of antigens that are shared by many subtypes.


An alternate approach to developing a universal flu vaccine has been to generate a multivalent vaccine (a vaccine with the ability to protect against several diseases or different strains of a single pathogen) that could encode all known subtypes of influenza virus. The study describing the findings was published in November in the journal Science. 


What are the types of influenza virus?


According to the Centers for Disease Control and Prevention (CDC), there are four types of influenza viruses, namely A, B, C and D. Almost every winter, influenza A and B virus strains cause seasonal epidemics of people in the United States. The time period during which people in the US are affected by influenza A and B virus strains is known as the flu season. 


What are seasonal influenza vaccines?


Currently available flu vaccines, known as seasonal influenza vaccines, offer little protection in people during the flu season because these vaccines help the immune system fight against only four strains of influenza virus. These are two influenza A strains and two B strains. Each year, the composition of seasonal flu vaccines is changed in accordance with forecasts of which strains are likely to make people sick during the coming season. 


Why it is difficult to develop seasonal influenza vaccines


It is uncertain which influenza virus subtype will cause the next pandemic, and hence, it is difficult to create effective pre-pandemic vaccines. 


All about the universal flu vaccine candidate that provided protection against 20 influenza strains


As part of the new study, Claudia P Arevalo from the University of Pennsylvania, Philadelphia, United States, along with other researchers, took advantage of recent advances in nucleic acid-based vaccine platforms to develop a lipid nanoparticle vaccine which consists of messenger RNA whose nucleoside has been modified. A nucleoside consists of sugar and nitrogenous bases, while a nucleotide contains sugar, nitrogenous base and a phosphate group. 


This vaccine candidate encodes hemagglutinin antigens from all 20 known influenza A and B virus strains, the study said. The researchers immunised mice and ferrets. The vaccine candidate elicited high levels of cross-reactive and subtype-specific antibodies in both animals. Cross-reactivity is a phenomenon in which an antibody raised against a particular antigen is able to initiate an immune reaction against a different antigen. Therefore, the vaccine protected the animals from matched and mismatched influenza virus strains. 


The vaccine candidate developed as part of the study reacted to all 20 encoded antigens. Therefore, vaccination was able to protect mice and ferrets challenged with matched and mismatched viral strains. This means that mRNA vaccines can provide protection against antigenically variable viruses by simultaneously inducing antibodies against multiple antigens, the authors concluded in the study. 


Multivalent vaccines must be designed in a way such that they help the immune system protect the body against any strain of a particular pathogen. 


How the vaccine candidate was developed


In order to develop this mRNA vaccine candidate, the researchers relied on the same mRNA technology that is used in Covid-19 vaccines. However, the researchers started working on this vaccine in 2017, years before the Covid-19 pandemic began. This research helped lay the groundwork for Covid-19 vaccines, a CNN report said. 


The idea behind the research was to identify one or two areas that do not change much from strain to strain, in order to train the immune system to make antibodies against these regions, and protect people from multiple viruses simultaneously.


The study focused on making a vaccine which could encode for hemagglutinin, a protein present in each of the 20 known strains of influenza virus. 


This protein is similar to the spike protein of SARS-CoV-2, according to Scott Hensley, senior author on the new paper, the CNN report said. 


Before making a vaccine candidate which could develop high levels of antibodies against all 20 strains, the researchers vaccinated mice with every antigen they wanted to include in the vaccine to make sure that each antigen elicited an immune response. 


According to the report, each strain was delivered in a 2.5-milligram dose, which means that overall, the vaccine candidate included a 50-milligram dose of mRNA. 


In order to see whether the vaccine selectively boosted antibodies in mice that had been previously infected with influenza, the researchers tested the shots in mice that had never been exposed to influenza, and in mice that had previously been infected with H1N1 flu virus strains similar to or different from the strains included in the vaccine. 


Findings of the study


The researchers observed that not only did the vaccine boost already existing antibodies in mice that had previously been infected with influenza virus, but also generated new antibodies to viral proteins that the immune systems of the mice were unfamiliar to. 


For the mice that were exposed to strains very similar to the ones they had earlier been infected with, the antibodies generated neutralised only the viral strains. 


However, the mice that were exposed to strains less similar to the ones that had earlier been infected fell sick, and started recovering seven or eight days after infection. 


The mice injected with a placebo vaccine, which carried mRNA instructions to make an unrelated enzyme, died after exposure to the strains.


Other universal flu vaccines undergoing development


One universal flu vaccine is undergoing development and testing at the US National Institutes of Health (NIH). Healthy adults aged 18 to 55 years, who do not smoke and have not received a flu vaccine in the eight weeks prior, or a Covid-19 vaccine in the four weeks prior to enrollment are eligible for participating in clinical trials of the universal flu vaccine being developed by NIH.