Low immunogenicity predicted for emerging avian-origin H7N9

Figures & data

Figure 1. The rapid emergence of H7N9 in several locations in China reflects wide-spread distribution in the animal population and potential for even greater spread. H7N9 is a virus that deserves serious consideration. Should a traveler get infected in China, flight routes from the outbreak regions would quickly carry any human-transmissible virus to huge population centers in Europe, North America and Asia. An estimated 70% of the world population resides within two hours’ travel time of destination airports (calculated using gridded population-density maps and a data set of global travel times, map supplied by A. J. Tatem, Z. Huang and S. I. Hay (2013). Unpublished data. (A.J.T., University of Southampton, UK; Z.H., University of Florida, Gainesville; S.I.H., University of Oxford, UK.) Reprinted by permission from Macmillan Publishers Ltd: Nature News 2013.⁹

Figure 2. Potential immunogenicity of emerging influenza A (H7N9) HA and HA from the current seasonal vaccine and H7 vaccines. The number of HLA ligands (putative T cell epitopes) per unit protein is plotted on an Immunogenicity Scale. This scale is correlated with observed immunogenicity in retrospective and prospective studies.^16,17 The numbers used in this scale reflect the difference between the number of predicted T cell epitopes we would expect to find in a protein of any given size by chance alone (based on an evaluation of more than 10,000 random protein sequences) and the number of putative epitopes predicted by the EpiMatrix System for a given protein. The EpiMatrix Protein Score of an “average” protein is zero. EpiMatrix Protein Scores above zero indicate the presence of excess MHC ligands and denote a higher potential for immunogenicity, while scores below zero indicate the presence of fewer potential HLA ligands than expected and a lower potential for immunogenicity. H7 has fewer HLA ligands than expected, which is reflected in its negative immunogenicity score. Seasonal strains of influenza are scored for potential immunogenicity on the left; their scores are much higher than H7N9.

Table 1. Numbers of putative class II ICS constructed from the four emerging avian H7N9 strains and numbers of those epitopes conserved (at least 80% amino acid similarity) in recently circulating and vaccine backbone influenza strains

H7N9    Ag	Putative epitopes	Published	Other H7N9	2012–2013 vaccine strains		2013–2014 vaccine recommendations		Vaccine backbone
				A/California/    7/2009    (H1N1)	A/Victoria/    361/2011 (H3N2)	A/Christchurch/    16/2010    (H1N1)	A/Texas/    50/2012    (H3N2)	TIV	LAIV
								A/Puerto Rico/    8/34 (H1N1)	A/Ann Arbor/7/67 (H2N2)
HA	11	0	10	1	3	2	3
M1	9	6	9	9	9	9	9	9	9
M2	2	0	2	2	2	2	2	2	2
NA	6	0	5	0	1	0	1
NEP	6	0	5	6	6	--	6	6	6
NP	11	8	11	9*	11	--	11	11	11
NS1	3	0	2	3	3	--	3	3	3
PA	14	0	14	14	14	--	14	14	14
PB1	18	2	17	18	18	--	18	18	18
PB1-F2	1	0	1	--	0	--	0	1	1
PB2	20	0	20	20	20	--	20	20	20

Counts of published epitopes from IEDB mapped to H7N9 ICS are shown in the third column. Table values marked with ‘--‘ represent an antigen (Ag) that was unavailable for download. It can be easily seen that peptides from HA and NA are less conserved among other strains than epitopes derived from the internal proteins. *A/California/7/2009 NP sequence accessed from GISAID was truncated and did not cover C-terminal NP ICS.

Table 2. Numbers of putative class I epitopes discovered in four emerging avian H7N9 strains and numbers of those epitopes conserved (at least 80% amino acid similarity) in recently circulating and vaccine backbone influenza strains

H7N9 Ag	Putative epitopes	Published	Other H7N9	2012/2013 vaccine strains		2013/2014 vaccine recommendations		Vaccine backbone
				A/California/ 7/2009 (H1N1)	A/Victoria/ 361/2011 (H3N2)	A/Christchurch/ 16/2010 (H1N1)	A/Texas/ 50/2012 (H3N2)	TIV	LAIV
								A/Puerto Rico/    8/34 (H1N1)	A/Ann Arbor/7/67 (H2N2)
HA	150	0	122	2	2	2	2
M1	89	17	52	55	45	55	45	53	45
M2	53	0	38	26	22	26	22	21	19
NA	146	0	130	1	1	1	1
NEP	53	1	45	12	20	–	20	26	30
NP	146	8	126	59*	59	–	60	77	67
NS1	91	1	32	18	15	–	15	27	21
PA	150	6	130	115	103	–	104	118	109
PB1	150	15	137	111	115	–	115	111	123
PB1-F2	64	0	15	–	0	–	0	3	4
PB2	150	0	140	123	90	–	90	103	110

Counts of published epitopes from IEDB mapped to H7N9 epitopes discovered here are shown in the third column. Table values marked with ‘–‘ represent an antigen (Ag) that was unavailable for download. Epitope sequences from HA and NA are less conserved among other strains than epitopes derived from the internal proteins. *A/California/7/2009 NP sequence accessed from GISAID was truncated and did not cover C-terminal NP ICS.

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