​​FutureFlu

Tracking H1N1pdm

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2017-03-07. BLASTP Comparison of A/Michigan/45/2015 (recommended by WHO) and A/Montana/04/2016 (recommended by FutureFlu) showing 100% identities and zero gaps proving that the two vaccines are identical

Antigenic Drift between A/Michigan/45/2015 and representative members of Clade 6B.2

      A/Brisbane/294/2016 | A/HongKong/90/2016 | A/Israel/Q-504/2015 | A/SouthAustralia/121/2016
      >         N101S                                N101S                          N101S                            N101S
      >         V169T                                V169T                          V169T                            V169T
      >         N179S                                N179S                          N179S                            N179S
                 D185N                         
      >         V190I                                 V190I                           V190I                             V190I
      >         T233I                                 T233I                           T233I                             T233I
                  A278S                               A278S                                                                A278S
      >         E508G                               E508G                          E508G                            E508G
      >         D518E                               D518E                          D518E                            D518E

The computed antigenic distance is less that 0.25 Antigenic Units, which is within acceptable limit. N101S, V169T, N179S, V190I, T233I, E508G and D518E, highlighted by the chevrons, are the major mutational differences between the two Clades. Of these, N179S is significant because it eliminates a potential N-linked glycosylation site. The amino acid pattern of a potential glycosylation site is NXS/T or NXXS/T. The mutation replaces the arginine with serine, thus disrupting the pattern.

2017-03-01. Comparison of Clade 6B.1 with A/California/07/2009 and A/Montana/04/2016

Synonymous differences between the genomes of A/Michigan/45/2015 (MI15)  and A/Montana/04/2016 (MT16)

    Coordinate  MI15    MT16      Coded

                Codon   Codon   Amino Acid

       ​047      AAC     AAT          N
       131      GAG     GAA          E
       177      CTT     CTC          L
       313      CCG     CCA          P
       317      GGA     GGG          G
       337      GTT     GTC          V
       526      ATT     ATC          I
       554      TGC     TGT          C

All coordinates (i.e. amino acid or nucleotide locations in a sequence) in the following discussion are in the HA1 frame of reference. Hemagglutinin comprises 566 peptides, which are signal peptide (17 aa) + HA1 (327 aa) + HA2 (222 aa), where aa = amino acids.

 

This research has focused on the HA1 segment because it contains the receptor-binding and antigenic domains and is therefore, the target of all flu vaccines. HA1 and HA2 are hinged by an alpha-helical coiled coil and linked by two cysteine residues, forming intramonomer disulfide bridges in a prestressed hairpin conformation. The cytoplasmic proteasomes and proton pumps in the membrane of the endocytic vesicles (containing the virus) lower the endosomal pH, cleaving the HA1-HA2 hinge, disassociating HA1 from HA2 and making it virulent.

The mutations in the following text are listed in the customary notation. For example, S101N refers to the mutation from S (serine) to N (asparagine) at the coordinate 101 of the HA1 segment.

2017-04-20. ​Antigenic Drift between A/Michigan/45/2015 and Clade 6B.2

CA09: A/California/07/2009 like, current vaccine

MT16: A/Montana/04/2016 like, proposed by FutureFlu


​HI Titers computed with the Antigenic Prediction Model:

Clade 6B.1 antigen against CA09 antiserum = 1,142

​Clade 6B.1 antigen against MT16 antiserum = 2,616

​Autologous titer = 2,560


​Antigenic drifts between Clade 6B.1 and

  ● CA09 = |1 - log2 (1142) / log2 (2560)| = 1.03 AU

  ● MT16 = |1 - log2 (2616) / log2 (2560)| = 0.03 AU


With an antigenic distance greater than 1 Antigenic Unit, CA09 has drifted from the prevalent strains, while MT16 is highly aligned with Clade 6B.1 (= 0.03 AU). It is also evident in the phylogenetic tree of the clade (on left) including the vaccine candidates (shown in yellow).