Haemophilus influenzae vaccine candidate outer membrane protein P6 is not conserved in all strains

Figures & data

Figure 1 P6 NMR structure (Protein Data Bank ID 2AIZ) with residues 59 and 61 highlighted in ball-and-stick, prepared using PyMOL Molecular Viewer. Copyright 2009 DeLano Scientific LLC.

Figure 2 ELISA results showing the binding of monoclonal antibody 7F3 with standard deviation bars. NTHi HH13 and H. haemolyticus did not show any reactivity with mAb 7F3. HH22 and HH1 are representative of all of the variant P6 isolates tested.

Table 1 Amino acid sequence variation of all isolates that did not have 100% amino acid homology with either typical NTHi or H. haemolyticus

	Source	AA11	AA33	AA42	AA59^a	AA61^a	AA77	AA81	AA114	AA152
Typical NTHi	N/A	Ala	Ala	Ala	Asp	Thr	Ala	Ala	Ala	Ala
Invasive Urogenital^b	N/A	Ala	Gly	Ser	Asn	Glu	Ala	Ala	Ala	Ser
HH13	OP	Ala	Gly	Ala	Asn	Glu	Ala	Ala	Ala	Ala
HH22	OP	Ala	Gly	Ala	Asp	Thr	Ala	Ala	Ala	Ala
HH39	OP	Ala	Gly	Ala	Asp	Thr	Ala	Ala	Ala	Ala
HH75	OP	Ala	Gly	Ala	Asp	Thr	Ala	Ala	Ala	Ala
HH77	OP	Ala	Gly	Ala	Asp	Thr	Ala	Ala	Ala	Ala
HH86	OP	Ala	Gly	Ala	Asp	Thr	Ala	Ala	Ala	Ala
HH2	NP	Ala	Ala	Ala	Asp	Thr	Ala	Thr	Ala	Ser
HH5	NP	Ala	Ala	Ala	Asp	Thr	Ala	Ala	Thr	N/D
HH40	MEF	Ala	Ala	Ala	Asp	Thr	Ala	Thr	Ala	N/D
HH67	OP	Ala	Ala	Ala	Asp	Thr	Ala	Ala	Thr	Ala
HH69	OP	Ala	Ala	Ala	Asp	Thr	Glu	Ala	Ala	Ala
HH70	OP	Ala	Ala	Ala	Asp	Thr	Glu	Ala	Ala	Ala
HH80	OP	Ala	Ala	Ala	Asp	Thr	Ala	Ala	Thr	Ala
HH88	OP	Thr	Ala	Ala	Asp	Thr	Ala	Ala	Ala	Ala

Source abbreviations are defined as OP is oropharyngeal; NP is nasopharyngeal; MEF is Middle Ear fluid; N/A is not applicable. The sequence reaction for HH5 and HH40 did not cover the region for amino acid 152 (N/O). Shaded cells indicate amino acid differences from typical NTHi. Note: ^aAA 59 and AA 61 of omp P6 is part of the epitope that binds mAB 7F3. ^bThe invasive urogenital amino acid pattern is from the reported unique NTHi isolate by Murphy et al.7

Murphy TF, Kirkham C, Sikkema DJ. Neonatal, urogenital isolates of biotype 4 nontypeable Haemophilus influenzae express a variant P6 outer membrane protein molecule. Infect Immun 1992; 60:2016 - 2022

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