Novel adeno-associated virus vector vaccine restricts replication of simian immunodeficiency virus in macaques.
Gene transfer vectors based on recombinant adeno-associated virus (rAAV) are simple, versatile, and safe. While the conventional applications for rAAV vectors have focused on delivery of therapeutic genes, we have developed the system for delivery of vaccine antigens. In particular, we are interested in generating rAAV vectors for use as a prophylactic human immunodeficiency virus type 1 (HIV-1) vaccine. To that end, we constructed vaccine vectors that expressed genes from the simian immunodeficiency virus (SIV) for evaluation in the monkey SIV model. After a single intramuscular dose, rAAV/SIV vaccines elicited SIV-specific T cells and antibodies in macaques. Furthermore, immunized animals were able to significantly restrict replication of a live, virulent SIV challenge. These data suggest that rAAV vaccine vectors induced biologically relevant immune responses, and thus, warrant continued development as a viable HIV-1 vaccine candidate.
Johnson
Philip R
PR
Columbus Children's Hospital, Room WA3011, 700 Children's Dr., Columbus, OH 43205, USA. johnsonp@pediatrics.ohio-state.edu
Schnepp
Bruce C
BC
Connell
Mary J
MJ
Rohne
Daniela
D
Robinson
Suzanne
S
Krivulka
Georgia R
GR
Lord
Carol I
CI
Zinn
Rebekah
R
Montefiori
David C
DC
Letvin
Norman L
NL
Clark
K Reed
KR
D000818:Animals; D000229:Dependovirus / Q000235:genetics* / Q000276:immunology; D005822:Genetic Vectors; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D008253:Macaca mulatta; D009500:Neutralization Tests; D018449:SAIDS Vaccines / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D019444:Vaccines, DNA / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*; D014779:Virus Replication
D015395:Histocompatibility Antigens Class I; C110764:Mamu-A 01 antigen; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic