Norovirus P particle, a novel platform for vaccine development and antibody production.
The norovirus P particle is an octahedral nanoparticle formed by 24 copies of the protrusion (P) domain of the norovirus capsid protein. This P particle is easily produced in Escherichia coli, extremely stable, and highly immunogenic. There are three surface loops per P domain, making a total of 72 loops per particle, and these are potential sites for foreign antigen presentation for immune enhancement. To prove this concept, a small peptide (His tag, 7 amino acids [aa]) and a large antigen (rotavirus VP8, 159 aa) were inserted into one of the loops. Neither insertion affects P particle formation, while both antigens were presented well on the P particle surface. The immune-enhancement effect of the P particle was demonstrated by significantly increased antibody titers induced by the P particle-presented antigens compared to the titers induced by free antigens. In addition, the measured neutralization antibody titers and levels of protection against rotavirus shedding in mice immunized with the VP8 chimeric P particles were significantly higher than those of mice immunized with the free VP8 antigen. Sera from P particle-VP8 chimera-vaccinated animals also blocked norovirus virus-like particle (VLP) binding to the histo-blood group antigen (HBGA) receptors. From these data, the P particle appears to be an excellent vaccine platform for antigen presentation. The readily available three surface loops and the great capacity for foreign antigen insertion make this platform attractive for wide application in vaccine development and antibody production. The P particle-VP8 chimeras may serve as a dual vaccine against both rotavirus and norovirus.
Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
Ming
M
Tan
Pengwei
P
Huang
Ming
M
Xia
Ping-An
PA
Fang
Weiming
W
Zhong
Monica
M
McNeal
Chao
C
Wei
Wen
W
Jiang
Xi
X
Jiang
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D005822:Genetic Vectors; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D029322:Norovirus / Q000235:genetics*; D022243:Rotavirus Vaccines / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D022721:Vaccines, Virosome / Q000235:genetics / Q000276:immunology
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022243:Rotavirus Vaccines; D014614:Vaccines, Synthetic; D022721:Vaccines, Virosome