Influenza immunization elicits antibodies specific for an egg-adapted vaccine strain.
For broad protection against infection by viruses such as influenza or HIV, vaccines should elicit antibodies that bind conserved viral epitopes, such as the receptor-binding site (RBS). RBS-directed antibodies have been described for both HIV and influenza virus, and the design of immunogens to elicit them is a goal of vaccine research in both fields. Residues in the RBS of influenza virus hemagglutinin (HA) determine a preference for the avian or human receptor, α-2,3-linked sialic acid and α-2,6-linked sialic acid, respectively. Transmission of an avian-origin virus between humans generally requires one or more mutations in the sequences encoding the influenza virus RBS to change the preferred receptor from avian to human, but passage of a human-derived vaccine candidate in chicken eggs can select for reversion to avian receptor preference. For example, the X-181 strain of the 2009 new pandemic H1N1 influenza virus, derived from the A/California/07/2009 isolate and used in essentially all vaccines since 2009, has arginine at position 226, a residue known to confer preference for an α-2,3 linkage in H1 subtype viruses; the wild-type A/California/07/2009 isolate, like most circulating human H1N1 viruses, has glutamine at position 226. We describe, from three different individuals, RBS-directed antibodies that recognize the avian-adapted H1 strain in current influenza vaccines but not the circulating new pandemic 2009 virus; Arg226 in the vaccine-strain RBS accounts for the restriction. The polyclonal sera of the three donors also reflect this preference. Therefore, when vaccines produced from strains that are never passaged in avian cells become widely available, they may prove more capable of eliciting RBS-directed, broadly neutralizing antibodies than those produced from egg-adapted viruses, extending the established benefits of current seasonal influenza immunizations.
Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School.
Donald D
DD
Raymond
Seqirus, 45 Sidney St., Cambridge, Massachusetts, USA.
Shaun M
SM
Stewart
Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
Jiwon
J
Lee
Seqirus, 45 Sidney St., Cambridge, Massachusetts, USA.
Jack
J
Ferdman
Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School.
Goran
G
Bajic
Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School.
Khoi T
KT
Do
Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School.|Graduate Program in Virology, Harvard Medical School, Boston, Massachusetts, USA.
Michael J
MJ
Ernandes
Seqirus, 45 Sidney St., Cambridge, Massachusetts, USA.
Pirada
P
Suphaphiphat
Seqirus, 45 Sidney St., Cambridge, Massachusetts, USA.
Ethan C
EC
Settembre
Seqirus, 45 Sidney St., Cambridge, Massachusetts, USA.
Philip R
PR
Dormitzer
Novartis Vaccines and Diagnostics, Siena, Italy.
Giuseppe
G
Del Giudice
Novartis Vaccines and Diagnostics, Siena, Italy.
Oretta
O
Finco
Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.
Tae Hyun
TH
Kang
Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.
Gregory C
GC
Ippolito
Department of Chemical Engineering, University of Texas at Austin, Austin, Texas, USA.|Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas, USA.|Center of Systems and Synthetic Biology, University of Texas at Austin, Austin, Texas, USA.|Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, USA.
George
G
Georgiou
Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts, USA.
Thomas B
TB
Kepler
Duke Human Vaccine Institute, Duke University Medical School, Durham, North Carolina, USA.|Department of Medicine, Duke University Medical School, Durham, North Carolina, USA.
Barton F
BF
Haynes
Duke Human Vaccine Institute, Duke University Medical School, Durham, North Carolina, USA.|Department of Pediatrics, Duke University Medical School, Durham, North Carolina, USA.
M Anthony
MA
Moody
Duke Human Vaccine Institute, Duke University Medical School, Durham, North Carolina, USA.|Department of Medicine, Duke University Medical School, Durham, North Carolina, USA.
Hua-Xin
HX
Liao
Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School.
Aaron G
AG
Schmidt
Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School.|Howard Hughes Medical Institute, Boston, Massachusetts, USA.
Stephen C
SC
Harrison
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D002645:Chickens; D003460:Crystallization; D004285:Dogs; D004531:Eggs; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D000071497:Immunogenicity, Vaccine / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D005585:Influenza in Birds / Q000821:virology; D007251:Influenza, Human / Q000517:prevention & control* / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D010950:Plasma Cells / Q000276:immunology; D017434:Protein Structure, Tertiary; D012794:Sialic Acids / Q000276:immunology*
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D012794:Sialic Acids