DNA vaccination in rhesus macaques induces potent immune responses and decreases acute and chronic viremia after SIVmac251 challenge.
Optimized plasmid DNAs encoding the majority of SIVmac239 proteins and delivered by electroporation (EP) elicited strong immune responses in rhesus macaques. Vaccination decreased viremia in both the acute and chronic phases of infection after challenge with pathogenic SIVmac251. Two groups of macaques were vaccinated with DNA plasmids producing different antigen forms, "native" and "modified," inducing distinct immune responses. Both groups showed significantly lower viremia during the acute phase of infection, whereas the group immunized with the native antigens showed better protection during the chronic phase (1.7 log decrease in virus load, P = 0.009). Both groups developed strong cellular and humoral responses against the DNA vaccine antigens, which included Gag, Pol, Env, Nef, and Tat. Vaccination induced both central memory and effector memory T cells that were maintained at the day of challenge, suggesting the potential for rapid mobilization upon virus challenge. The group receiving the native antigens developed higher and more durable anti-Env antibodies, including neutralizing antibodies at the day of challenge. These results demonstrate that DNA vaccination in the absence of any heterologous boost can provide protection from high viremia comparable to any other vaccine modalities tested in this macaque model.
Rosati
Margherita
M
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA.
Bergamaschi
Cristina
C
Valentin
Antonio
A
Kulkarni
Viraj
V
Jalah
Rashmi
R
Alicea
Candido
C
Patel
Vainav
V
von Gegerfelt
Agneta S
AS
Montefiori
David C
DC
Venzon
David J
DJ
Khan
Amir S
AS
Draghia-Akli
Ruxandra
R
Van Rompay
Koen K A
KK
Felber
Barbara K
BK
Pavlakis
George N
GN
D000208:Acute Disease; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000235:genetics; D002908:Chronic Disease; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000628:therapy*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D014766:Viremia / Q000276:immunology / Q000517:prevention & control*
D000914:Antibodies, Viral; D000956:Antigens, Viral; D018449:SAIDS Vaccines; D019444:Vaccines, DNA