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Macaques vaccinated with live-attenuated SIV control replication of heterologous virus.

Reynolds MR, Weiler AM, Weisgrau KL, Piaskowski SM, Furlott JR, Weinfurter JT, Kaizu M, Soma T, León EJ, MacNair C, Leaman DP, Zwick MB, Gostick E, Musani SK, Price DA, Friedrich TC, Rakasz EG, Wilson NA, McDermott AB, Boyle R, Allison DB, Burton DR, Koff WC, Watkins DI - J. Exp. Med. (2008)

Bottom Line: An effective AIDS vaccine will need to protect against globally diverse isolates of HIV.Vaccinees reduced viral replication by approximately 2 logs between weeks 2-32 (P < or = 0.049) postchallenge.On a more positive note, our results suggest that MHC-I-restricted CD8(+) T cells contribute to the protection induced by the live-attenuated SIV vaccine and demonstrate that vaccine-induced CD8(+) T cell responses can control replication of heterologous challenge viruses.

View Article: PubMed Central - PubMed

Affiliation: AIDS Vaccine Research Laboratory, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA. mrreynol@wisc.edu

ABSTRACT
An effective AIDS vaccine will need to protect against globally diverse isolates of HIV. To address this issue in macaques, we administered a live-attenuated simian immunodeficiency virus (SIV) vaccine and challenged with a highly pathogenic heterologous isolate. Vaccinees reduced viral replication by approximately 2 logs between weeks 2-32 (P < or = 0.049) postchallenge. Remarkably, vaccinees expressing MHC-I (MHC class I) alleles previously associated with viral control completely suppressed acute phase replication of the challenge virus, implicating CD8(+) T cells in this control. Furthermore, transient depletion of peripheral CD8(+) lymphocytes in four vaccinees during the chronic phase resulted in an increase in virus replication. In two of these animals, the recrudescent virus population contained only the vaccine strain and not the challenge virus. Alarmingly, however, we found evidence of recombinant viruses emerging in some of the vaccinated animals. This finding argues strongly against an attenuated virus vaccine as a solution to the AIDS epidemic. On a more positive note, our results suggest that MHC-I-restricted CD8(+) T cells contribute to the protection induced by the live-attenuated SIV vaccine and demonstrate that vaccine-induced CD8(+) T cell responses can control replication of heterologous challenge viruses.

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Virus replication in Mamu-B*17+ macaques. Plasma virus concentrations in SIVmac239Δnef vaccinated (blue) and unvaccinated (red) Mamu-B*17+ macaques for 60 wk p.c.
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fig6: Virus replication in Mamu-B*17+ macaques. Plasma virus concentrations in SIVmac239Δnef vaccinated (blue) and unvaccinated (red) Mamu-B*17+ macaques for 60 wk p.c.

Mentions: We also investigated viral evolution in the two vaccinated Mamu-B*17+ animals. These animals controlled virus replication at two weeks p.c. below 250 vRNA copy Eq/ml plasma but subsequently experienced near-identical increases in plasma virus replication with respect to time and magnitude (Fig. 6). We detected the same amino acid changes in the two Mamu-B*17–restricted Env epitopes in both animals, Env816-825LY10 (Env LY10) and Env830-838FW9 (Env FW9; Table II). Curiously, the mutations observed in these two epitopes were nearly identical to the sequence of SIVmac239Δnef, with only a histidine-to-tyrosine substitution in Env FW9 differing from the SIVmac239Δnef sequence in these animals.


Macaques vaccinated with live-attenuated SIV control replication of heterologous virus.

Reynolds MR, Weiler AM, Weisgrau KL, Piaskowski SM, Furlott JR, Weinfurter JT, Kaizu M, Soma T, León EJ, MacNair C, Leaman DP, Zwick MB, Gostick E, Musani SK, Price DA, Friedrich TC, Rakasz EG, Wilson NA, McDermott AB, Boyle R, Allison DB, Burton DR, Koff WC, Watkins DI - J. Exp. Med. (2008)

Virus replication in Mamu-B*17+ macaques. Plasma virus concentrations in SIVmac239Δnef vaccinated (blue) and unvaccinated (red) Mamu-B*17+ macaques for 60 wk p.c.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2571929&req=5

fig6: Virus replication in Mamu-B*17+ macaques. Plasma virus concentrations in SIVmac239Δnef vaccinated (blue) and unvaccinated (red) Mamu-B*17+ macaques for 60 wk p.c.
Mentions: We also investigated viral evolution in the two vaccinated Mamu-B*17+ animals. These animals controlled virus replication at two weeks p.c. below 250 vRNA copy Eq/ml plasma but subsequently experienced near-identical increases in plasma virus replication with respect to time and magnitude (Fig. 6). We detected the same amino acid changes in the two Mamu-B*17–restricted Env epitopes in both animals, Env816-825LY10 (Env LY10) and Env830-838FW9 (Env FW9; Table II). Curiously, the mutations observed in these two epitopes were nearly identical to the sequence of SIVmac239Δnef, with only a histidine-to-tyrosine substitution in Env FW9 differing from the SIVmac239Δnef sequence in these animals.

Bottom Line: An effective AIDS vaccine will need to protect against globally diverse isolates of HIV.Vaccinees reduced viral replication by approximately 2 logs between weeks 2-32 (P < or = 0.049) postchallenge.On a more positive note, our results suggest that MHC-I-restricted CD8(+) T cells contribute to the protection induced by the live-attenuated SIV vaccine and demonstrate that vaccine-induced CD8(+) T cell responses can control replication of heterologous challenge viruses.

View Article: PubMed Central - PubMed

Affiliation: AIDS Vaccine Research Laboratory, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USA. mrreynol@wisc.edu

ABSTRACT
An effective AIDS vaccine will need to protect against globally diverse isolates of HIV. To address this issue in macaques, we administered a live-attenuated simian immunodeficiency virus (SIV) vaccine and challenged with a highly pathogenic heterologous isolate. Vaccinees reduced viral replication by approximately 2 logs between weeks 2-32 (P < or = 0.049) postchallenge. Remarkably, vaccinees expressing MHC-I (MHC class I) alleles previously associated with viral control completely suppressed acute phase replication of the challenge virus, implicating CD8(+) T cells in this control. Furthermore, transient depletion of peripheral CD8(+) lymphocytes in four vaccinees during the chronic phase resulted in an increase in virus replication. In two of these animals, the recrudescent virus population contained only the vaccine strain and not the challenge virus. Alarmingly, however, we found evidence of recombinant viruses emerging in some of the vaccinated animals. This finding argues strongly against an attenuated virus vaccine as a solution to the AIDS epidemic. On a more positive note, our results suggest that MHC-I-restricted CD8(+) T cells contribute to the protection induced by the live-attenuated SIV vaccine and demonstrate that vaccine-induced CD8(+) T cell responses can control replication of heterologous challenge viruses.

Show MeSH
Related in: MedlinePlus