An optimized SIV DNA vaccine can serve as a boost for Ad5 and provide partial protection from a high-dose SIVmac251 challenge

Natalie A. Hutnick, Devin J F Myles, Lauren Hirao, Veronica L. Scott, Bernadette Ferraro, Amir S. Khan, Mark G. Lewis, Chris J Miller, Andrew J. Bett, Danilo Casimiro, Niranjan Y. Sardesai, J. Joseph Kim, John Shiver, David B. Weiner

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)3202-3208
Number of pages7
JournalVaccine
Volume30
Issue number21
DOIs
StatePublished - May 2 2012

Fingerprint

SAIDS Vaccines
DNA Vaccines
recombinant vaccines
T-lymphocytes
DNA
T-Lymphocytes
dosage
Cellular Immunity
cell-mediated immunity
vaccines
AIDS Vaccines
animals
Electroporation
electroporation
HLA-DR Antigens
Serology
Macaca mulatta
Haplorhini
monkeys
flow cytometry

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

Hutnick, N. A., Myles, D. J. F., Hirao, L., Scott, V. L., Ferraro, B., Khan, A. S., ... Weiner, D. B. (2012). An optimized SIV DNA vaccine can serve as a boost for Ad5 and provide partial protection from a high-dose SIVmac251 challenge. Vaccine, 30(21), 3202-3208. https://doi.org/10.1016/j.vaccine.2012.02.069

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 journalArticle

Hutnick, NA, Myles, DJF, Hirao, L, Scott, VL, Ferraro, B, Khan, AS, Lewis, MG, Miller, CJ, Bett, AJ, Casimiro, D, Sardesai, NY, Kim, JJ, Shiver, J & Weiner, DB 2012, 'An optimized SIV DNA vaccine can serve as a boost for Ad5 and provide partial protection from a high-dose SIVmac251 challenge', Vaccine, vol. 30, no. 21, pp. 3202-3208. https://doi.org/10.1016/j.vaccine.2012.02.069
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. / An optimized SIV DNA vaccine can serve as a boost for Ad5 and provide partial protection from a high-dose SIVmac251 challenge. In: Vaccine. 2012 ; Vol. 30, No. 21. pp. 3202-3208.
@article{669451a8f883467ab38642f3e8bda174,
title = "An optimized SIV DNA vaccine can serve as a boost for Ad5 and provide partial protection from a high-dose SIVmac251 challenge",
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.",
keywords = "Adenovirus 5 vaccine, DNA vaccine, SIV",
author = "Hutnick, {Natalie A.} and Myles, {Devin J F} and Lauren Hirao and Scott, {Veronica L.} and Bernadette Ferraro and Khan, {Amir S.} and Lewis, {Mark G.} and Miller, {Chris J} and Bett, {Andrew J.} and Danilo Casimiro and Sardesai, {Niranjan Y.} and Kim, {J. Joseph} and John Shiver and Weiner, {David B.}",
year = "2012",
month = "5",
day = "2",
doi = "10.1016/j.vaccine.2012.02.069",
language = "English (US)",
volume = "30",
pages = "3202--3208",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier BV",
number = "21",

}

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 -