Peptide vaccination using nonionic block copolymers induces protective anti-viral CTL responses.
High molecular weight nonionic block copolymers have been developed as vaccine adjuvants. We employed these adjuvants in water-in-oil emulsion and multiple emulsion formulations with a synthetic peptide-based antigen vaccine to test their ability to prime anti-viral CD8(+) T cell responses. Vaccines were made using the H-2(d)-restricted immunodominant peptide from lymphocytic choriomeningitis virus (LCMV), NP118-126, and administered to BALB/c ByJ (H-2(d)) mice. Peptide-containing emulsions were able to induce NP118-126 specific CTL and IFN-gamma secreting CD8(+) T cells in the vaccinated mice and these responses were maintained for at least 90 days post immunization. At all times, the responses induced by the copolymer formulations were equal to, or better than, formulations based on incomplete Freund's adjuvant (IFA). In addition, the responses induced by prophylactic vaccination using the multiple emulsion formulation resulted in accelerated viral clearance following infection with a strain of LCMV (clone 13) that causes a persistent infection in naïve adult mice. These results indicate that peptide vaccination using a formulation based on high molecular weight nonionic block copolymer in a simple water-in-oil or a multiple emulsion format can induce virus-specific CD8(+) T cell responses and confer protection sufficient enough to prevent the establishment of a persistent infection.
Lanier
J G
JG
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, G211 Rollins Research Center, Atlanta, GA 30322, USA.
Newman
M J
MJ
Lee
E M
EM
Sette
A
A
Ahmed
R
R
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D004655:Emulsions; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010446:Peptide Fragments / Q000276:immunology*; D011108:Polymers; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D014758:Viral Core Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D000276:Adjuvants, Immunologic; C113154:CRL 1005; D004655:Emulsions; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D010446:Peptide Fragments; D011108:Polymers; D014758:Viral Core Proteins; D014765:Viral Vaccines; D007371:Interferon-gamma