tetano
Editor, Senior Moderator
Vaccine
Available online 2 October 2012
In Press, Uncorrected Proof ? Note to users
Cover image
Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform
Elizabeth S. Gabitzscha, Corresponding author contact information, E-mail the corresponding author,
Joseph P. Balint-Juniora,
Younong Xua,
Stephanie Balcaitisa,
Brigitte Sanders-Beerb,
Julie Karlc,
Kent J. Weinholdd,
Frank R. Jonesa
a Etubics Corporation, Seattle, WA 98119, United States
b BioQual, Inc., Rockville, MD, United States
c Wisconsin National Primate Research Center, Madison, WI, United States
d Duke University, Durham, NC, United States
http://dx.doi.org/10.1016/j.vaccine.2012.09.058
Abstract
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.
Highlights
► Immunization with Ad5 [E1-, E2b-] results in antigen specific immune induction in Ad5 immune NHP. ► Vaccination with Ad5 [E1-, E2b-]-SIV resulted in significant viral control as compared to controls. ► Immune responses were induced to a second pathogen, H1N1, in the hyper Ad5 immune NHP. ► Ad5 [E1-, E2b-] platform is effective regardless of pre-existing and concomitant vector immunity.
http://www.sciencedirect.com/science/article/pii/S0264410X12013783
Available online 2 October 2012
In Press, Uncorrected Proof ? Note to users
Cover image
Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform
Elizabeth S. Gabitzscha, Corresponding author contact information, E-mail the corresponding author,
Joseph P. Balint-Juniora,
Younong Xua,
Stephanie Balcaitisa,
Brigitte Sanders-Beerb,
Julie Karlc,
Kent J. Weinholdd,
Frank R. Jonesa
a Etubics Corporation, Seattle, WA 98119, United States
b BioQual, Inc., Rockville, MD, United States
c Wisconsin National Primate Research Center, Madison, WI, United States
d Duke University, Durham, NC, United States
http://dx.doi.org/10.1016/j.vaccine.2012.09.058
Abstract
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.
Highlights
► Immunization with Ad5 [E1-, E2b-] results in antigen specific immune induction in Ad5 immune NHP. ► Vaccination with Ad5 [E1-, E2b-]-SIV resulted in significant viral control as compared to controls. ► Immune responses were induced to a second pathogen, H1N1, in the hyper Ad5 immune NHP. ► Ad5 [E1-, E2b-] platform is effective regardless of pre-existing and concomitant vector immunity.
http://www.sciencedirect.com/science/article/pii/S0264410X12013783