Increased immune responses in rhesus macaques by DNA vaccination combined with electroporation.
We used optimized DNA expression vectors to compare two gene delivery methodologies in rhesus macaques, namely direct DNA injection and in vivo adaptive constant-current electroporation via the intramuscular route. The use of in vivo electroporation increased levels of gene expression and immune responses. We used an optimized HIV gag expression plasmid to show the development of new cellular immune responses in SIV-infected animals controlling viremia. Furthermore, after vaccination with SIV expression plasmids the recall responses to the SIV antigens were very high, indicating that DNA is a strong boost in the presence of antiretroviral treatment in SIV-infected animals. There was substantial animal-to-animal variability in DNA expression, revealed by plasma measurements of IL-15 produced by co-injected IL-15 DNA. IL-15 expression levels correlated with peak immune responses. Electroporation led to an expansion of antigen-specific CD4+ and CD8+ T cells of both central and effector memory phenotype. These results indicate that improved gene delivery and expression by electroporation dramatically increases immunogenicity of DNA vaccines. Electroporation is thus an important method to improve the effectiveness of DNA vaccination.
Rosati
Margherita
M
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702-1201, United States.
Valentin
Antonio
A
Jalah
Rashmi
R
Patel
Vainav
V
von Gegerfelt
Agneta
A
Bergamaschi
Cristina
C
Alicea
Candido
C
Weiss
Deborah
D
Treece
Jim
J
Pal
Ranajit
R
Markham
Phillip D
PD
Marques
Ernesto T A
ET
August
J Thomas
JT
Khan
Amir
A
Draghia-Akli
Ruxandra
R
Felber
Barbara K
BK
Pavlakis
George N
GN
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018274:Electroporation; D006801:Humans; D007156:Immunologic Memory; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D010957:Plasmids / Q000235:genetics; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014766:Viremia / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D054301:gag Gene Products, Human Immunodeficiency Virus