The science behind why the flu vaccine isn’t always effective

Blame mutation.

Overview

The flu is a respiratory illness that affects the nose, throat, and lungs. The typical symptoms of the flu are well-known and include aches, fever, headache, sore throat, cough, exhaustion, congestion, vomiting, and diarrhea. It is caused by the influenza virus, which comes in four types, known as influenza A, B, C, and D.

Influenza A and B are the most commonly-experienced types among humans; these viruses cause seasonal epidemics most winters in the United States. Influenza C is less common and can cause a mild respiratory illness. Influenza D primarily affects cattle; it’s not known to cause illness in humans.

Influenza A can be further broken down into subtypes based on proteins that occur on the surface of the virus. These proteins are hemagglutinin (abbreviated H) and neuraminidase (N). Hemagglutinin has 18 subtypes (H1 through H18), while neuraminidase has 11 subtypes (N1 through N11).

These subtypes present in different strains of the influenza virus. The current subtypes of influenza A found in humans are H1N1 and H3N2. This past year, H3N2 was the dominant strain; however, this is not always the case. For instance, in the spring of 2009, H1N1 caused illness in humans; it was different from the primary influenza A virus circulating at the time and caused the first flu pandemic in more than 40 years.

The primary method of protection against the flu is the flu vaccine. Flu vaccines introduce a person’s immune system to purified proteins from dead flu viruses; the antibodies made attack the flu viruses when the body comes in contact with them.

The proteins in the flu vaccine are typically purified from a virus grown in chicken eggs. When World Health Organization scientists choose the strains of influenza virus to make the yearly flu vaccine, they include two strains of influenza A (one variant of H1N1 and one variant of H3N2) and one or two strains of influenza B. These strains are chosen over a period of 6 months because the vaccines take that long to be manufactured and distributed.

However, the influenza virus mutates and it is very hard to predict which variant of influenza will make people sick during the flu season. For example, at the beginning of 2014–2015 flu season, a mutated version of H3N2 caused the majority of cases of the flu in the United States. The mutated virus was different from the strain of H3N2 that was included in that year’s flu vaccine and as a result the vaccine did not give much protection against the flu.

The effectiveness of the flu vaccine is a hot topic of recent research. H3N2 viruses continuously acquire mutation in the hemagglutinin glycoprotein, and new studies suggest that the lower effectiveness was due to a substitution at the hemagglutinin glycoprotein of the H3N2 virus. This mutation resulted in the year 2016’s flu vaccine being only 30 percent effective.

Another study showed that the lack of a glycosylation site, an area in which a carbohydrate attaches to the functional part of a protein, also reduced the effectiveness of the vaccine. Glycosylation is important for virus survival, and this demonstrates that the glycosylation site is necessary for binding of human antibodies. Better understanding of influenza cell-surface HA glycosylation will provide a positive direction for the design of a universal influenza vaccine.

Further Reading

Zost, S.J., et. al. PNAS. 114 (47), 12578 (2017).

Yang, H., et. al. Virology. 477, 18 (2015).

Nicholas, C.W. PLOS Pathogens. 13 (10), 1371 (2017).