TY - JOUR
T1 - Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform
AU - Gabitzsch, Elizabeth S.
AU - Balint-Junior, Joseph P.
AU - Xu, Younong
AU - Balcaitis, Stephanie
AU - Sanders-Beer, Brigitte
AU - Karl, Julie
AU - Weinhold, Kent J.
AU - Paessler, Slobodan
AU - Jones, Frank R.
N1 - Funding Information:
The authors would like to thank Dr. Daniel Barouch of the Harvard Medical School for contribution of the SIV- pol and SIV-gp140 env plasmids, Dr. Andrea Amalfitano for his consultation regarding vector development and Elizabeth Peters and Matt Collins for their assistance with the study. We also wish to thank Ms. Carol Jones for her management of NIH grant activities and ViraQuest, North Liberty, IA, USA for vaccine production. This work was supported in part by NIH-NIAID Grant 2R44A1071733 to Etubics Corporation. The MHC class I genotyping was supported by Etubics Corporation and performed at the Wisconsin National Primate Research Center with support from NIH-NIAID grant P51RR000167 . This publication's contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
PY - 2012/11/26
Y1 - 2012/11/26
N2 - Anti-vector immunity mitigates immune responses induced by recombinant adenovirus vector vaccines, limiting their prime-boost capabilities. We have developed a novel gene delivery and expression platform (Ad5 [E1-, E2b-]) that induces immune responses despite pre-existing and/or developed concomitant Ad5 immunity. In the present study, we evaluated if this new Ad5 platform could overcome the adverse condition of pre-existing Ad5 immunity to induce effective immune responses in prime-boost immunization regimens against two different infectious diseases in the same animal. Ad5 immune rhesus macaques (RM) were immunized multiple times with the Ad5 [E1-, E2b-] platform expressing antigens from simian immunodeficiency virus (SIV). Immunized RM developed cell-mediated immunity against SIV antigens Gag, Pol, Nef and Env as well as antibody against Env. Vaccinated and vector control RMs were challenged intra-rectally with homologous SIVmac239. During a 7-week follow-up, there was perturbation of SIV load in some immunized RM. At 7 weeks post-challenge, eight immunized animals (53%) did not have detectable SIV, compared to two RM controls (13%) (P< 0.02; log-rank Mantel-Cox test). There was no correlation of protective MHC contributing to infection control. The RM without detectable circulating SIV, now hyper immune to Ad5, were then vaccinated with the same Ad5 [E1-, E2b-] platform expressing H1N1 influenza hemagglutinin (HA). Thirty days post Ad5 [E1-, E2b-]-HA vaccination, significant levels of influenza neutralizing antibody were induced in all animals that increased after an Ad5 [E1-, E2b-]-HA homologous boost. These data demonstrate the versatility of this new vector platform to immunize against two separate disease targets in the same animal despite the presence of immunity against the delivery platform, permitting homologous repeat immunizations with an Ad5 gene delivery platform.
AB - Anti-vector immunity mitigates immune responses induced by recombinant adenovirus vector vaccines, limiting their prime-boost capabilities. We have developed a novel gene delivery and expression platform (Ad5 [E1-, E2b-]) that induces immune responses despite pre-existing and/or developed concomitant Ad5 immunity. In the present study, we evaluated if this new Ad5 platform could overcome the adverse condition of pre-existing Ad5 immunity to induce effective immune responses in prime-boost immunization regimens against two different infectious diseases in the same animal. Ad5 immune rhesus macaques (RM) were immunized multiple times with the Ad5 [E1-, E2b-] platform expressing antigens from simian immunodeficiency virus (SIV). Immunized RM developed cell-mediated immunity against SIV antigens Gag, Pol, Nef and Env as well as antibody against Env. Vaccinated and vector control RMs were challenged intra-rectally with homologous SIVmac239. During a 7-week follow-up, there was perturbation of SIV load in some immunized RM. At 7 weeks post-challenge, eight immunized animals (53%) did not have detectable SIV, compared to two RM controls (13%) (P< 0.02; log-rank Mantel-Cox test). There was no correlation of protective MHC contributing to infection control. The RM without detectable circulating SIV, now hyper immune to Ad5, were then vaccinated with the same Ad5 [E1-, E2b-] platform expressing H1N1 influenza hemagglutinin (HA). Thirty days post Ad5 [E1-, E2b-]-HA vaccination, significant levels of influenza neutralizing antibody were induced in all animals that increased after an Ad5 [E1-, E2b-]-HA homologous boost. These data demonstrate the versatility of this new vector platform to immunize against two separate disease targets in the same animal despite the presence of immunity against the delivery platform, permitting homologous repeat immunizations with an Ad5 gene delivery platform.
KW - Ad5 [E1-, E2b-]
KW - Ad5 immunity
KW - Adenovirus vector
KW - HIV vaccine
KW - SIVmac239
UR - http://www.scopus.com/inward/record.url?scp=84869876506&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84869876506&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2012.09.058
DO - 10.1016/j.vaccine.2012.09.058
M3 - Article
C2 - 23041546
AN - SCOPUS:84869876506
SN - 0264-410X
VL - 30
SP - 7265
EP - 7270
JO - Vaccine
JF - Vaccine
IS - 50
ER -