Abstract
Gene gun-based DNA immunization alone or in combination With recombinant vaccinia vectors was evaluated for the ability to elicit protective immune responses in rhesus macaques challenged with a pathogenic, heterologous simian immunodeficiency virus (SIV). Six monkeys primed with seven consecutive doses of DNA encoding SIV(mac239) gp120 and gp160 (DNA+DNA) were divided into two groups. Three of these animals received another DNA booster immunization and the remaining three received a booster immunization containing a homologous, live recombinant vaccinia virus expressing SIV(mac251) gp160 (DNA+VAC). In addition, a group of 15 animals primed with recombinant vaccinia vectors were divided into two groups. One group of six monkeys received another immunization of vaccinia (VAC+VAC) and the other nine animals received a DNA (mac239) booster immunization (VAC+DNA). Geometric mean end-point IgG titres in the DNA+VAC and VAC+DNA groups were substantially higher than the responses seen in the VAC+VAC and DNA+DNA groups, demonstrating a synergistic relationship between DNA-based vaccines and recombinant vaccinia virus-based vaccines. All vaccinates and five naive controls were challenged 19 weeks after the final booster immunization with 10 animal infectious doses of SIV(Delta/B670). The vaccines did not prevent infection. However, all vaccine groups showed significant virus load reductions from seven to 56 days post challenge when compared to controls. Although the DNA+DNA group developed the lowest prechallenge antibody responses, the most significant reduction (200-fold) in virus load was associated with this group. In addition, a significant delay in CD4+ T cell loss relative to controls was observed in the DNA+DNA group. These results demonstrate that a gene gun-based DNA vaccine provided some attenuation of infection and CD4+ T cell loss after a heterologous challenge.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 389-396 |
| Number of pages | 8 |
| Journal | Immunology and Cell Biology |
| Volume | 75 |
| Issue number | 4 |
| State | Published - 1997 |
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Keywords
- Gene gun
- Nucleic acid immunization
- Recombinant vaccinia virus
- Rhesus macaque
- SIV
ASJC Scopus subject areas
- Immunology
- Clinical Biochemistry
- Cell Biology
Cite this
Gene gun-based nucleic acid immunization alone or in combination with recombinant vaccinia vectors suppresses virus burden in rhesus macaques challenged with a heterologous SIV. / Fuller, Deborah Heydenburg; Simpson, Laura; Cole, Kelly Stefano; Clements, Janice E; Panicali, Dennis L.; Montelaro, Ronald C.; Murphey-Corb, Michael; Haynes, Joel R.
In: Immunology and Cell Biology, Vol. 75, No. 4, 1997, p. 389-396.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Gene gun-based nucleic acid immunization alone or in combination with recombinant vaccinia vectors suppresses virus burden in rhesus macaques challenged with a heterologous SIV
AU - Fuller, Deborah Heydenburg
AU - Simpson, Laura
AU - Cole, Kelly Stefano
AU - Clements, Janice E
AU - Panicali, Dennis L.
AU - Montelaro, Ronald C.
AU - Murphey-Corb, Michael
AU - Haynes, Joel R.
PY - 1997
Y1 - 1997
N2 - Gene gun-based DNA immunization alone or in combination With recombinant vaccinia vectors was evaluated for the ability to elicit protective immune responses in rhesus macaques challenged with a pathogenic, heterologous simian immunodeficiency virus (SIV). Six monkeys primed with seven consecutive doses of DNA encoding SIV(mac239) gp120 and gp160 (DNA+DNA) were divided into two groups. Three of these animals received another DNA booster immunization and the remaining three received a booster immunization containing a homologous, live recombinant vaccinia virus expressing SIV(mac251) gp160 (DNA+VAC). In addition, a group of 15 animals primed with recombinant vaccinia vectors were divided into two groups. One group of six monkeys received another immunization of vaccinia (VAC+VAC) and the other nine animals received a DNA (mac239) booster immunization (VAC+DNA). Geometric mean end-point IgG titres in the DNA+VAC and VAC+DNA groups were substantially higher than the responses seen in the VAC+VAC and DNA+DNA groups, demonstrating a synergistic relationship between DNA-based vaccines and recombinant vaccinia virus-based vaccines. All vaccinates and five naive controls were challenged 19 weeks after the final booster immunization with 10 animal infectious doses of SIV(Delta/B670). The vaccines did not prevent infection. However, all vaccine groups showed significant virus load reductions from seven to 56 days post challenge when compared to controls. Although the DNA+DNA group developed the lowest prechallenge antibody responses, the most significant reduction (200-fold) in virus load was associated with this group. In addition, a significant delay in CD4+ T cell loss relative to controls was observed in the DNA+DNA group. These results demonstrate that a gene gun-based DNA vaccine provided some attenuation of infection and CD4+ T cell loss after a heterologous challenge.
AB - Gene gun-based DNA immunization alone or in combination With recombinant vaccinia vectors was evaluated for the ability to elicit protective immune responses in rhesus macaques challenged with a pathogenic, heterologous simian immunodeficiency virus (SIV). Six monkeys primed with seven consecutive doses of DNA encoding SIV(mac239) gp120 and gp160 (DNA+DNA) were divided into two groups. Three of these animals received another DNA booster immunization and the remaining three received a booster immunization containing a homologous, live recombinant vaccinia virus expressing SIV(mac251) gp160 (DNA+VAC). In addition, a group of 15 animals primed with recombinant vaccinia vectors were divided into two groups. One group of six monkeys received another immunization of vaccinia (VAC+VAC) and the other nine animals received a DNA (mac239) booster immunization (VAC+DNA). Geometric mean end-point IgG titres in the DNA+VAC and VAC+DNA groups were substantially higher than the responses seen in the VAC+VAC and DNA+DNA groups, demonstrating a synergistic relationship between DNA-based vaccines and recombinant vaccinia virus-based vaccines. All vaccinates and five naive controls were challenged 19 weeks after the final booster immunization with 10 animal infectious doses of SIV(Delta/B670). The vaccines did not prevent infection. However, all vaccine groups showed significant virus load reductions from seven to 56 days post challenge when compared to controls. Although the DNA+DNA group developed the lowest prechallenge antibody responses, the most significant reduction (200-fold) in virus load was associated with this group. In addition, a significant delay in CD4+ T cell loss relative to controls was observed in the DNA+DNA group. These results demonstrate that a gene gun-based DNA vaccine provided some attenuation of infection and CD4+ T cell loss after a heterologous challenge.
KW - Gene gun
KW - Nucleic acid immunization
KW - Recombinant vaccinia virus
KW - Rhesus macaque
KW - SIV
UR - http://www.scopus.com/inward/record.url?scp=0030886653&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030886653&partnerID=8YFLogxK
M3 - Article
C2 - 9315483
AN - SCOPUS:0030886653
VL - 75
SP - 389
EP - 396
JO - Immunology and Cell Biology
JF - Immunology and Cell Biology
SN - 0818-9641
IS - 4
ER -