A virus-like particle that elicits cross-reactive antibodies to the conserved stem of influenza virus hemagglutinin.
The discovery of broadly neutralizing antibodies that recognize highly conserved epitopes in the membrane-proximal region of influenza virus hemagglutinin (HA) has revitalized efforts to develop a universal influenza virus vaccine. This effort will likely require novel immunogens that contain these epitopes but lack the variable and immunodominant epitopes located in the globular head of HA. As a first step toward developing such an immunogen, we investigated whether the 20-residue A-helix of the HA2 chain that forms the major component of the epitope of broadly neutralizing antibodies CR6261, F10, and others is sufficient by itself to elicit antibodies with similarly broad antiviral activity. Here, we report the multivalent display of the A-helix on icosahedral virus-like particles (VLPs) derived from the capsid of Flock House virus. Mice immunized with VLPs displaying 180 copies/particle of the A-helix produced antibodies that recognized trimeric HA and the elicited antibodies had binding characteristics similar to those of CR6261 and F10: they recognized multiple HA subtypes from group 1 but not from group 2. However, the anti-A-helix antibodies did not neutralize influenza virus. These results indicate that further engineering of the transplanted peptide is required and that display of additional regions of the epitope may be necessary to achieve protection.
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, USA.
Anette
A
Schneemann
Jeffrey A
JA
Speir
Gene S
GS
Tan
Reza
R
Khayat
Damian C
DC
Ekiert
Yumiko
Y
Matsuoka
Ian A
IA
Wilson
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood*; D003429:Cross Reactions; D004337:Drug Carriers / Q000008:administration & dosage; D005260:Female; D005822:Genetic Vectors; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D030381:Nodaviridae / Q000235:genetics; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D022721:Vaccines, Virosome / Q000008:administration & dosage / Q000276:immunology
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D004337:Drug Carriers; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic; D022721:Vaccines, Virosome