Lymph node targeted multi-epitope subunit vaccine promotes effective immunity to EBV in HLA-expressing mice
Dasari, Vijayendra; McNeil, Lisa K.; Beckett, Kirrilee; Solomon, Matthew; Ambalathingal, George; Thuy, T. Le; Panikkar, Archana; Smith, Caitlyn; Steinbuck, Martin P.; Jakubowski, Aniela; Seenappa, Lochana M.; Palmer, Erica; Zhang, Jeff; Haqq, Christopher M.; DeMuth, Peter C.; Khanna, Rajiv
The recent emergence of a causal link between Epstein-Barr virus (EBV) and multiple sclerosis has generated considerable interest in the development of an effective vaccine against EBV.
Here we describe a vaccine formulation based on a lymph node targeting Amphiphile vaccine adjuvant, Amphiphile-CpG, admixed with EBV gp350 glycoprotein and an engineered EBV polyepitope protein that includes 20 CD8 + T cell epitopes from EBV latent and lytic antigens. Potent gp350-specific IgG responses are induced in mice with titers >100,000 in Amphiphile-CpG vaccinated mice. Immunization including Amphiphile-CpG also induces high frequencies of polyfunctional gp350specific CD4 + T cells and EBV-specific CD8 + T cells that are 2-fold greater than soluble CpG and are maintained for >7 months post immunization.
This combination of broad humoral and cellular immunity against multiple viral determinants is likely to provide better protection against primary infection and control of latently infected B cells leading to protection against the development of EBV-associated diseases.
Link | PDF (Nature Communications)
Dasari, Vijayendra; McNeil, Lisa K.; Beckett, Kirrilee; Solomon, Matthew; Ambalathingal, George; Thuy, T. Le; Panikkar, Archana; Smith, Caitlyn; Steinbuck, Martin P.; Jakubowski, Aniela; Seenappa, Lochana M.; Palmer, Erica; Zhang, Jeff; Haqq, Christopher M.; DeMuth, Peter C.; Khanna, Rajiv
The recent emergence of a causal link between Epstein-Barr virus (EBV) and multiple sclerosis has generated considerable interest in the development of an effective vaccine against EBV.
Here we describe a vaccine formulation based on a lymph node targeting Amphiphile vaccine adjuvant, Amphiphile-CpG, admixed with EBV gp350 glycoprotein and an engineered EBV polyepitope protein that includes 20 CD8 + T cell epitopes from EBV latent and lytic antigens. Potent gp350-specific IgG responses are induced in mice with titers >100,000 in Amphiphile-CpG vaccinated mice. Immunization including Amphiphile-CpG also induces high frequencies of polyfunctional gp350specific CD4 + T cells and EBV-specific CD8 + T cells that are 2-fold greater than soluble CpG and are maintained for >7 months post immunization.
This combination of broad humoral and cellular immunity against multiple viral determinants is likely to provide better protection against primary infection and control of latently infected B cells leading to protection against the development of EBV-associated diseases.
Link | PDF (Nature Communications)