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Fig. 1.  Phylogenetic tree of A/H1N1 flu virus

Components of Flu Vaccine

As mentioned in the Section Identifying  Drug Targets, the flu virus has four types (A-D), 18 variations of H (H1-H18) and 11 variations of N (N1-N11). Only Types A and B affect humans. Of all the combinations of H and N for Type A, humans are most often affected by A/H1N1 and A/H3N2. Therefore, the annual flu vaccine contains these two strains. In addition, there are two Type B strains, Yamagata and Victoria. Labs worldwide monitor how these four strains are evolving during the year before determining the most appropriate strains for the upcoming year's vaccine. For instance, the vaccine for the 2020-21 flu season was announced by WHO/CDC in March 2020. It was based on the work done in the labs during 2019. Components of the 2020-21 vaccine were

  • H1N1: A/Guangdong-Maonan/SWL1536/2019

  • H3N2: A/Hong Kong/2671/2019

  • Victoria: B/Washington/02/2019

  • Yamagata: B/Phuket/3073/2013

So, the annual flu vaccine specifies a list of four virus strains. These strains are changed as needed, to keep up with the mutations in flu virus. The vaccine manufacturers culture these strains, inactivate the resulting viruses and then create the vaccine from them.

Clades of
Flu Virus

Type B flu viruses do not have an animal host. As a result, our immune system can handle them well, Even if one falls sick with a Type B infection, the symptoms are mild. Therefore, most research focuses on A/H1N1 and A/H3N2. The currently active clades of A/H1N1 are shown in Figure 1. All clades in the figure originate from 6B.1A. Due to the constant adaptation of our immune system, other clades of A/H1N1 have ceased to be an issue. Some of the key mutations in each clade are also listed in the figure. For example, 6B.1A5A contains K130N and L161I mutations. To recap, K130N implies that N (arginine) has replaced K (lysine) at location 130.  Further, 6B.1A5A and 6B.1A5B share a common ancestor and mutations N129D and T185I. In comparison, the H3N2 strains currently circulating are grouped into Clades 3C.2a, 3C.2a1b, 3C.2a3 a and 3C.3a, 


Fig. 1.  Phylogenetic tree showing the evolution of hemagglutinin in A/H3N2 strain 

Evolution of H3N2

It may be recalled that spike protein is being tracked for COVID-19 because that is the target of vaccines. Similarly, hemagglutinin (H) protein is being tracked here for flu vaccines. As discussed in the Section Identifying Drug Targets, all flu vaccines are developed against hemagglutinin. The evolution of hemagglutinin of H3N2 is shown in Figure 1. There is a similar analysis for A/H1N1. which has not been presented.

  • Honingsbaum, M. (2020). Revisiting the 1957 and 1968 influenza pandemics. The Lancet. 395(10240), P1824-1826.

  • Jester, B et al. (2020) Fifty Years of Influenza A(H3N2) Following the Pandemic of 1968. American Journal of Public Health. 110(5). 669-676.

  • Sun, H et al. (2020). Prevalent Eurasian avian-like H1N1 swine influenza virus with 2009 pandemic viral genes facilitating human infection. PNAS.,117(29)., 17204-17210.

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