Polyanhydride Nanovaccines Induce Germinal Center B Cell Formation and Sustained Serum Antibody Responses.
Biodegradable polymeric nanoparticle-based subunit vaccines have shown promising characteristics by enhancing antigen presentation and inducing protective immune responses when compared with soluble protein. Specifically, polyanhydride nanoparticle-based vaccines (i.e., nanovaccines) have been shown to successfully encapsulate and release antigens, activate B and T cells, and induce both antibody- and cell-mediated immunity towards a variety of immunogens. One of the characteristics of strong thymus-dependent antibody responses is the formation of germinal centers (GC) and the generation of GC B cells, which is part of the T helper cell driven cellular response. In order to further understand the role of nanovaccines in the induction of antigen-specific immune responses, their ability to induce germinal center B cell formation and isotype switching and the effects thereof on serum antibody responses were investigated in these studies. Polyanhydride nanovaccines based on 1,6-bis(p-carboxyphenoxy)hexane and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane were used to subcutaneously administer a viral antigen. GC B cell formation and serum antibody responses induced by the nanovaccines were compared to that induced by alum-based vaccine formulations. It was demonstrated that a single dose of polyanhydride nanovaccines resulted in the formation of robust GCs and serum antibody in comparison to that induced by the alum-based formulation. This was attributed to the sustained release of antigen provided by the nanovaccines. When administered in a multiple dose regimen, the highest post-immunization titer and GC B cell number was enhanced, and the immune response induced by the nanovaccines was further sustained. These studies provide foundational information on the mechanism of action of polyanhydride nanovaccines.
Julia E
JE
Vela Ramirez
Lorraine T
LT
Tygrett
Jihua
J
Hao
Habtom H
HH
Habte
Michael W
MW
Cho
Neil S
NS
Greenspan
Thomas J
TJ
Waldschmidt
Balaji
B
Narasimhan
D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D018858:Germinal Center / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology / Q000379:methods; D049388:Polyanhydrides / Q000737:chemistry*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology*
D000906:Antibodies; D049388:Polyanhydrides; D022223:Vaccines, Subunit