Defining criteria for oligomannose immunogens for HIV using icosahedral virus capsid scaffolds.
The broadly neutralizing antibody 2G12 recognizes a conserved cluster of high-mannose glycans on the surface envelope spike of HIV, suggesting that the "glycan shield" defense of the virus can be breached and may, under the right circumstances, serve as a vaccine target. In an attempt to recreate features of the glycan shield semisynthetically, oligomannosides were coupled to surface lysines on the icosahedral capsids of bacteriophage Q beta and cowpea mosaic virus (CPMV). The Q beta glycoconjugates, but not CPMV, presented oligomannose clusters that bind the antibody 2G12 with high affinity. However, antibodies against these 2G12 epitopes were not detected in immunized rabbits. Rather, alternative oligomannose epitopes on the conjugates were immunodominant and elicited high titers of anti-mannose antibodies that do not crossreact with the HIV envelope. The results presented reveal important design considerations for a carbohydrate-based vaccine component for HIV.
Astronomo
Rena D
RD
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Kaltgrad
Eiton
E
Udit
Andrew K
AK
Wang
Sheng-Kai
SK
Doores
Katie J
KJ
Huang
Cheng-Yuan
CY
Pantophlet
Ralph
R
Paulson
James C
JC
Wong
Chi-Huey
CH
Finn
M G
MG
Burton
Dennis R
DR
D016915:AIDS Vaccines / Q000737:chemistry* / Q000276:immunology; D017908:Allolevivirus / Q000737:chemistry / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000080908:Broadly Neutralizing Antibodies; D002213:Capsid / Q000737:chemistry / Q000276:immunology*; D002240:Carbohydrate Sequence; D017798:Comovirus / Q000737:chemistry / Q000276:immunology*; D006678:HIV / Q000276:immunology*; D015483:HIV Antibodies; D015658:HIV Infections / Q000517:prevention & control; D008358:Mannose / Q000737:chemistry / Q000276:immunology*; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry / Q000276:immunology; D011817:Rabbits
C529157:2G12 monoclonal antibody; D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D000080908:Broadly Neutralizing Antibodies; D015483:HIV Antibodies; D009844:Oligosaccharides; D008358:Mannose