Abstract
One limitation in the development of an improved cellular response needed for an effective HIV-vaccine is the inability to induce robust effector T-cells capable of suppressing a heterologous challenge. To improve cellular immune responses, we examined the ability of an optimized DNA vaccine to boost the cellular immune responses induced by a highly immunogenic Ad5 prime. Five Chinese rhesus macaques received pVax encoding consensus (con) gag/pol/env intramuscularly (IM) with electroporation followed by the Merck Ad5 gag/pol/nef vaccine. A second group of five animals were vaccinated with Merck Ad5 gag/pol/nef followed by pVax gag/pol/env. One year following vaccination, Ad5-prime DNA-boosted monkeys and four unvaccinated controls received an intrarectal challenge with 1000 ID50 SIV mac251. The quality and magnitude of the T-cell response was analyzed by ELISpot and polyfunctional flow cytometry. We observed that an Ad5-prime DNA-boost resulted in significantly elevated SIV-specific T-cell responses even compared with animals receiving a DNA-prime Ad5-boost. Ad5 prime DNA boosted animals were capable of suppressing a pathogenic SIV mac251 challenge. Peak control correlated with the expansion of HLA-DR + CD8 + T-cells two weeks post-infection. These data illustrate that high optimization of a DNA vaccine can drive of immune responses primed by a robust vector system. This previously unachievable feature of these newly optimized DNAs warrants future studies of this strategy that may circumvent issues of serology associated with viral vector prime-boost systems.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3202-3208 |
| Number of pages | 7 |
| Journal | Vaccine |
| Volume | 30 |
| Issue number | 21 |
| DOIs | |
| State | Published - May 2 2012 |
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Keywords
- Adenovirus 5 vaccine
- DNA vaccine
- SIV
ASJC Scopus subject areas
- Immunology and Microbiology(all)
- Infectious Diseases
- Public Health, Environmental and Occupational Health
- veterinary(all)
- Molecular Medicine
Cite this
An optimized SIV DNA vaccine can serve as a boost for Ad5 and provide partial protection from a high-dose SIVmac251 challenge. / Hutnick, Natalie A.; Myles, Devin J F; Hirao, Lauren; Scott, Veronica L.; Ferraro, Bernadette; Khan, Amir S.; Lewis, Mark G.; Miller, Chris J; Bett, Andrew J.; Casimiro, Danilo; Sardesai, Niranjan Y.; Kim, J. Joseph; Shiver, John; Weiner, David B.
In: Vaccine, Vol. 30, No. 21, 02.05.2012, p. 3202-3208.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - An optimized SIV DNA vaccine can serve as a boost for Ad5 and provide partial protection from a high-dose SIVmac251 challenge
AU - Hutnick, Natalie A.
AU - Myles, Devin J F
AU - Hirao, Lauren
AU - Scott, Veronica L.
AU - Ferraro, Bernadette
AU - Khan, Amir S.
AU - Lewis, Mark G.
AU - Miller, Chris J
AU - Bett, Andrew J.
AU - Casimiro, Danilo
AU - Sardesai, Niranjan Y.
AU - Kim, J. Joseph
AU - Shiver, John
AU - Weiner, David B.
PY - 2012/5/2
Y1 - 2012/5/2
N2 - One limitation in the development of an improved cellular response needed for an effective HIV-vaccine is the inability to induce robust effector T-cells capable of suppressing a heterologous challenge. To improve cellular immune responses, we examined the ability of an optimized DNA vaccine to boost the cellular immune responses induced by a highly immunogenic Ad5 prime. Five Chinese rhesus macaques received pVax encoding consensus (con) gag/pol/env intramuscularly (IM) with electroporation followed by the Merck Ad5 gag/pol/nef vaccine. A second group of five animals were vaccinated with Merck Ad5 gag/pol/nef followed by pVax gag/pol/env. One year following vaccination, Ad5-prime DNA-boosted monkeys and four unvaccinated controls received an intrarectal challenge with 1000 ID50 SIV mac251. The quality and magnitude of the T-cell response was analyzed by ELISpot and polyfunctional flow cytometry. We observed that an Ad5-prime DNA-boost resulted in significantly elevated SIV-specific T-cell responses even compared with animals receiving a DNA-prime Ad5-boost. Ad5 prime DNA boosted animals were capable of suppressing a pathogenic SIV mac251 challenge. Peak control correlated with the expansion of HLA-DR + CD8 + T-cells two weeks post-infection. These data illustrate that high optimization of a DNA vaccine can drive of immune responses primed by a robust vector system. This previously unachievable feature of these newly optimized DNAs warrants future studies of this strategy that may circumvent issues of serology associated with viral vector prime-boost systems.
AB - One limitation in the development of an improved cellular response needed for an effective HIV-vaccine is the inability to induce robust effector T-cells capable of suppressing a heterologous challenge. To improve cellular immune responses, we examined the ability of an optimized DNA vaccine to boost the cellular immune responses induced by a highly immunogenic Ad5 prime. Five Chinese rhesus macaques received pVax encoding consensus (con) gag/pol/env intramuscularly (IM) with electroporation followed by the Merck Ad5 gag/pol/nef vaccine. A second group of five animals were vaccinated with Merck Ad5 gag/pol/nef followed by pVax gag/pol/env. One year following vaccination, Ad5-prime DNA-boosted monkeys and four unvaccinated controls received an intrarectal challenge with 1000 ID50 SIV mac251. The quality and magnitude of the T-cell response was analyzed by ELISpot and polyfunctional flow cytometry. We observed that an Ad5-prime DNA-boost resulted in significantly elevated SIV-specific T-cell responses even compared with animals receiving a DNA-prime Ad5-boost. Ad5 prime DNA boosted animals were capable of suppressing a pathogenic SIV mac251 challenge. Peak control correlated with the expansion of HLA-DR + CD8 + T-cells two weeks post-infection. These data illustrate that high optimization of a DNA vaccine can drive of immune responses primed by a robust vector system. This previously unachievable feature of these newly optimized DNAs warrants future studies of this strategy that may circumvent issues of serology associated with viral vector prime-boost systems.
KW - Adenovirus 5 vaccine
KW - DNA vaccine
KW - SIV
UR - http://www.scopus.com/inward/record.url?scp=84862807944&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84862807944&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2012.02.069
DO - 10.1016/j.vaccine.2012.02.069
M3 - Article
C2 - 22406458
AN - SCOPUS:84862807944
VL - 30
SP - 3202
EP - 3208
JO - Vaccine
JF - Vaccine
SN - 0264-410X
IS - 21
ER -