Human chemokine MIP1[alpha] increases efficiency of targeted DNA fusion vaccines

Efficacy of DNA vaccination has been improved in mice by fusion vaccines targeting antigen to antigen-presenting cells (APC) via chemokine receptors. Here, we aimed at extending this strategy to large animals and humans. Fusion proteins equipped with human MIP1α (LD78β isoform) retained functional a...

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Bibliographic Details
Published inVaccine Vol. 29; no. 2; p. 191
Main Authors Ruffini, Pier Adelchi, Grødeland, Gunnveig, Fredriksen, Agnete B, Bogen, Bjarne
Format Journal Article
LanguageEnglish
Published Kidlington Elsevier Limited 16.12.2010
Subjects
Amino acids
Chemokines
Deoxyribonucleic acid
DNA
Efficiency
Immunization
Lymphocytes
Proteins
Rodents
T cell receptors
Transgenic animals
Vaccines
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Summary:Efficacy of DNA vaccination has been improved in mice by fusion vaccines targeting antigen to antigen-presenting cells (APC) via chemokine receptors. Here, we aimed at extending this strategy to large animals and humans. Fusion proteins equipped with human MIP1α (LD78β isoform) retained functional activity and conformational correctness of targeting and antigenic units, respectively. Fusion proteins improved responses of cloned human CD4+ T cells, and a two amino acid NH2-truncated version of LD78β outperformed full length LD78β-vaccine proteinsin vitro. LD78β DNA fusion vaccines induced improved T cell (both CD4+ and CD8+) and antibody responses in mice following plasmid injection and skin electroporation. Finally, LD78β-vaccine proteins bound Rhesus macaque CCR5, setting the stage for targeted DNA immunization in non-human primates.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2010.10.057