This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wyand, M. S.
Right arrow Articles by Desrosiers, R. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wyand, M. S.
Right arrow Articles by Desrosiers, R. C.

 Previous Article  |  Next Article 

Journal of Virology, October 1999, p. 8356-8363, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Protection by Live, Attenuated Simian Immunodeficiency Virus against Heterologous Challenge

Michael S. Wyand,1 Kelledy Manson,1 David C. Montefiori,2 Jeffrey D. Lifson,3 R. Paul Johnson,4 and Ronald C. Desrosiers4,*

New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772-91024; Primedica, Worcester, Massachusetts 016081; Duke University Medical Center, Department of Surgery, Durham, North Carolina 277102; and AIDS Vaccine Program, SAIC---Frederick, NCI---Frederick Cancer Research and Development Center, Frederick, Maryland 217013

Received 3 May 1999/Accepted 9 July 1999

We examined the ability of a live, attenuated deletion mutant of simian immunodeficiency virus (SIV), SIVmac239Delta 3, which is missing nef and vpr genes, to protect against challenge by heterologous strains SHIV89.6p and SIVsmE660. SHIV89.6p is a pathogenic, recombinant SIV in which the envelope gene has been replaced by a human immunodeficiency virus type 1 envelope gene; other structural genes of SHIV89.6p are derived from SIVmac239. SIVsmE660 is an uncloned, pathogenic, independent isolate from the same primate lentivirus subgrouping as SIVmac but with natural sequence variation in all structural genes. The challenge with SHIV89.6p was performed by the intravenous route 37 months after the time of vaccination. By the criteria of CD4+ cell counts and disease, strong protection against the SHIV89.6p challenge was observed in four of four vaccinated monkeys despite the complete mismatch of env sequences. However, SHIV89.6p infection was established in all four previously vaccinated monkeys and three of the four developed fluctuating viral loads between 300 and 10,000 RNA copy equivalents per ml of plasma 30 to 72 weeks postchallenge. When other vaccinated monkeys were challenged with SIVsmE660 at 28 months after the time of vaccination, SIV loads were lower than those observed in unvaccinated controls but the level of protection was less than what was observed against SHIV89.6p in these experiments and considerably less than the level of protection against SIVmac251 observed in previous experiments. These results demonstrate a variable level of vaccine protection by live, attenuated SIVmac239Delta 3 against heterologous virus challenge and suggest that even live, attenuated vaccine approaches for AIDS will face significant hurdles in providing protection against the natural variation present in field strains of virus. The results further suggest that factors other than anti-Env immune responses can be principally responsible for the vaccine protection by live, attenuated SIV.

* Corresponding author. Mailing address: New England Regional Primate Research Center, Harvard Medical School, One Pine Hill Dr., Box 9102, Southborough, MA 01772-9102. Phone: (508) 624-8042. Fax: (508) 624-8190. E-mail: ronald_desrosiers{at}hms.harvard.edu.

Journal of Virology, October 1999, p. 8356-8363, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Korber, B. T., Letvin, N. L., Haynes, B. F. (2009). T-Cell Vaccine Strategies for Human Immunodeficiency Virus, the Virus with a Thousand Faces. J. Virol. 83: 8300-8314 [Full Text]  
  • Wilson, N. A., Keele, B. F., Reed, J. S., Piaskowski, S. M., MacNair, C. E., Bett, A. J., Liang, X., Wang, F., Thoryk, E., Heidecker, G. J., Citron, M. P., Huang, L., Lin, J., Vitelli, S., Ahn, C. D., Kaizu, M., Maness, N. J., Reynolds, M. R., Friedrich, T. C., Loffredo, J. T., Rakasz, E. G., Erickson, S., Allison, D. B., Piatak, M. Jr., Lifson, J. D., Shiver, J. W., Casimiro, D. R., Shaw, G. M., Hahn, B. H., Watkins, D. I. (2009). Vaccine-Induced Cellular Responses Control Simian Immunodeficiency Virus Replication after Heterologous Challenge. J. Virol. 83: 6508-6521 [Abstract] [Full Text]  
  • Sacha, J. B., Giraldo-Vela, J. P., Buechler, M. B., Martins, M. A., Maness, N. J., Chung, C., Wallace, L. T., Leon, E. J., Friedrich, T. C., Wilson, N. A., Hiraoka, A., Watkins, D. I. (2009). Gag- and Nef-specific CD4+ T cells recognize and inhibit SIV replication in infected macrophages early after infection. Proc. Natl. Acad. Sci. USA 106: 9791-9796 [Abstract] [Full Text]  
  • Yeh, W. W., Jaru-ampornpan, P., Nevidomskyte, D., Asmal, M., Rao, S. S., Buzby, A. P., Montefiori, D. C., Korber, B. T., Letvin, N. L. (2009). Partial Protection of Simian Immunodeficiency Virus (SIV)-Infected Rhesus Monkeys against Superinfection with a Heterologous SIV Isolate. J. Virol. 83: 2686-2696 [Abstract] [Full Text]  
  • Reynolds, M. R., Weiler, A. M., Weisgrau, K. L., Piaskowski, S. M., Furlott, J. R., Weinfurter, J. T., Kaizu, M., Soma, T., Leon, E. J., MacNair, C., Leaman, D. P., Zwick, M. B., Gostick, E., Musani, S. K., Price, D. A., Friedrich, T. C., Rakasz, E. G., Wilson, N. A., McDermott, A. B., Boyle, R., Allison, D. B., Burton, D. R., Koff, W. C., Watkins, D. I. (2008). Macaques vaccinated with live-attenuated SIV control replication of heterologous virus. JEM 205: 2537-2550 [Abstract] [Full Text]  
  • Berry, N., Stebbings, R., Ferguson, D., Ham, C., Alden, J., Brown, S., Jenkins, A., Lines, J., Duffy, L., Davis, L., Elsley, W., Page, M., Hull, R., Stott, J., Almond, N. (2008). Resistance to superinfection by a vigorously replicating, uncloned stock of simian immunodeficiency virus (SIVmac251) stimulates replication of a live attenuated virus vaccine (SIVmacC8). J. Gen. Virol. 89: 2240-2251 [Abstract] [Full Text]  
  • Walker, B. D., Burton, D. R. (2008). Toward an AIDS Vaccine. Science 320: 760-764 [Abstract] [Full Text]  
  • Mansfield, K., Lang, S. M., Gauduin, M.-C., Sanford, H. B., Lifson, J. D., Johnson, R. P., Desrosiers, R. C. (2008). Vaccine Protection by Live, Attenuated Simian Immunodeficiency Virus in the Absence of High-Titer Antibody Responses and High-Frequency Cellular Immune Responses Measurable in the Periphery. J. Virol. 82: 4135-4148 [Abstract] [Full Text]  
  • Giannecchini, S., Pistello, M., Isola, P., Matteucci, D., Mazzetti, P., Freer, G., Bendinelli, M. (2007). Role of Env in Resistance of Feline Immunodeficiency Virus (FIV)-Infected Cats to Superinfection by a Second FIV Strain as Determined by Using a Chimeric Virus. J. Virol. 81: 10474-10485 [Abstract] [Full Text]  
  • De Boer, R. J. (2007). Understanding the Failure of CD8+ T-Cell Vaccination against Simian/Human Immunodeficiency Virus. J. Virol. 81: 2838-2848 [Abstract] [Full Text]  
  • Amara, R. R., Patel, K., Niedziela, G., Nigam, P., Sharma, S., Staprans, S. I., Montefiori, D. C., Chenareddi, L., Herndon, J. G., Robinson, H. L., McClure, H. M., Novembre, F. J. (2005). A Combination DNA and Attenuated Simian Immunodeficiency Virus Vaccine Strategy Provides Enhanced Protection from Simian/Human Immunodeficiency Virus-Induced Disease. J. Virol. 79: 15356-15367 [Abstract] [Full Text]  
  • Stebbings, R., Berry, N., Waldmann, H., Bird, P., Hale, G., Stott, J., North, D., Hull, R., Hall, J., Lines, J., Brown, S., D'Arcy, N., Davis, L., Elsley, W., Edwards, C., Ferguson, D., Allen, J., Almond, N. (2005). CD8+ Lymphocytes Do Not Mediate Protection against Acute Superinfection 20 Days after Vaccination with a Live Attenuated Simian Immunodeficiency Virus. J. Virol. 79: 12264-12272 [Abstract] [Full Text]  
  • Broche-Pierre, S., Richardson, J., Moraillon, A., Sonigo, P. (2005). Evaluation of live feline immunodeficiency virus vaccines with modified antigenic properties. J. Gen. Virol. 86: 2495-2506 [Abstract] [Full Text]  
  • Evans, D. T., Bricker, J. E., Sanford, H. B., Lang, S., Carville, A., Richardson, B. A., Piatak, M. Jr., Lifson, J. D., Mansfield, K. G., Desrosiers, R. C. (2005). Immunization of Macaques with Single-Cycle Simian Immunodeficiency Virus (SIV) Stimulates Diverse Virus-Specific Immune Responses and Reduces Viral Loads after Challenge with SIVmac239. J. Virol. 79: 7707-7720 [Abstract] [Full Text]  
  • Craigo, J. K., Li, F., Steckbeck, J. D., Durkin, S., Howe, L., Cook, S. J., Issel, C., Montelaro, R. C. (2005). Discerning an Effective Balance between Equine Infectious Anemia Virus Attenuation and Vaccine Efficacy. J. Virol. 79: 2666-2677 [Abstract] [Full Text]  
  • Johnson, P. R., Schnepp, B. C., Connell, M. J., Rohne, D., Robinson, S., Krivulka, G. R., Lord, C. I., Zinn, R., Montefiori, D. C., Letvin, N. L., Clark, K. R. (2005). Novel Adeno-Associated Virus Vector Vaccine Restricts Replication of Simian Immunodeficiency Virus in Macaques. J. Virol. 79: 955-965 [Abstract] [Full Text]  
  • Choi, J., Walker, J., Boichuk, S., Kirkiles-Smith, N., Torpey, N., Pober, J. S., Alexander, L. (2005). Human Endothelial Cells Enhance Human Immunodeficiency Virus Type 1 Replication in CD4+ T Cells in a Nef-Dependent Manner In Vitro and In Vivo. J. Virol. 79: 264-276 [Abstract] [Full Text]  
  • Haaft, P. t., Verschoor, E. J., Verstrepen, B., Niphuis, H., Dubbes, R., Koornstra, W., Bogers, W., Rosenwirth, B., Heeney, J. L. (2004). Readily acquired secondary infections of human and simian immunodeficiency viruses following single intravenous exposure in non-human primates. J. Gen. Virol. 85: 3735-3745 [Abstract] [Full Text]  
  • Quinto, I., Puca, A., Greenhouse, J., Silvera, P., Yalley-Ogunro, J., Lewis, M. G., Palmieri, C., Trimboli, F., Byrum, R., Adelsberger, J., Venzon, D., Chen, X., Scala, G. (2004). High Attenuation and Immunogenicity of a Simian Immunodeficiency Virus Expressing a Proteolysis-resistant Inhibitor of NF-{kappa}B. J. Biol. Chem. 279: 1720-1728 [Abstract] [Full Text]  
  • Tsui, R., Herring, B. L., Barbour, J. D., Grant, R. M., Bacchetti, P., Kral, A., Edlin, B. R., Delwart, E. L. (2004). Human Immunodeficiency Virus Type 1 Superinfection Was Not Detected following 215 Years of Injection Drug User Exposure. J. Virol. 78: 94-103 [Abstract] [Full Text]  
  • Pistello, M., Matteucci, D., Bonci, F., Isola, P., Mazzetti, P., Zaccaro, L., Merico, A., Del Mauro, D., Flynn, N., Bendinelli, M. (2003). AIDS Vaccination Studies Using an Ex Vivo Feline Immunodeficiency Virus Model: Protection from an Intraclade Challenge Administered Systemically or Mucosally by an Attenuated Vaccine. J. Virol. 77: 10740-10750 [Abstract] [Full Text]  
  • Patterson, L. J., Malkevitch, N., Pinczewski, J., Venzon, D., Lou, Y., Peng, B., Munch, C., Leonard, M., Richardson, E., Aldrich, K., Kalyanaraman, V. S., Pavlakis, G. N., Robert-Guroff, M. (2003). Potent, Persistent Induction and Modulation of Cellular Immune Responses in Rhesus Macaques Primed with Ad5hr-Simian Immunodeficiency Virus (SIV) env/rev, gag, and/or nef Vaccines and Boosted with SIV gp120. J. Virol. 77: 8607-8620 [Abstract] [Full Text]  
  • Casimiro, D. R., Tang, A., Chen, L., Fu, T.-M., Evans, R. K., Davies, M.-E., Freed, D. C., Hurni, W., Aste-Amezaga, J. M., Guan, L., Long, R., Huang, L., Harris, V., Nawrocki, D. K., Mach, H., Troutman, R. D., Isopi, L. A., Murthy, K. K., Rice, K., Wilson, K. A., Volkin, D. B., Emini, E. A., Shiver, J. W. (2003). Vaccine-Induced Immunity in Baboons by Using DNA and Replication-Incompetent Adenovirus Type 5 Vectors Expressing a Human Immunodeficiency Virus Type 1 gag Gene. J. Virol. 77: 7663-7668 [Abstract] [Full Text]  
  • Alexander, L., Illyinskii, P. O., Lang, S. M., Means, R. E., Lifson, J., Mansfield, K., Desrosiers, R. C. (2003). Determinants of Increased Replicative Capacity of Serially Passaged Simian Immunodeficiency Virus with nef Deleted in Rhesus Monkeys. J. Virol. 77: 6823-6835 [Abstract] [Full Text]  
  • Chakrabarti, L. A., Metzner, K. J., Ivanovic, T., Cheng, H., Louis-Virelizier, J., Connor, R. I., Cheng-Mayer, C. (2002). A Truncated Form of Nef Selected during Pathogenic Reversion of Simian Immunodeficiency Virus SIVmac239{Delta}nef Increases Viral Replication. J. Virol. 77: 1245-1256 [Abstract] [Full Text]  
  • Goulder, P. J.R., Walker, B. D. (2002). HIV-1 Superinfection -- A Word of Caution. NEJM 347: 756-758 [Full Text]  
  • Horton, H., Vogel, T. U., Carter, D. K., Vielhuber, K., Fuller, D. H., Shipley, T., Fuller, J. T., Kunstman, K. J., Sutter, G., Montefiori, D. C., Erfle, V., Desrosiers, R. C., Wilson, N., Picker, L. J., Wolinsky, S. M., Wang, C., Allison, D. B., Watkins, D. I. (2002). Immunization of Rhesus Macaques with a DNA Prime/Modified Vaccinia Virus Ankara Boost Regimen Induces Broad Simian Immunodeficiency Virus (SIV)-Specific T-Cell Responses and Reduces Initial Viral Replication but Does Not Prevent Disease Progression following Challenge with Pathogenic SIVmac239. J. Virol. 76: 7187-7202 [Abstract] [Full Text]  
  • Novitsky, V., Smith, U. R., Gilbert, P., McLane, M. F., Chigwedere, P., Williamson, C., Ndung'u, T., Klein, I., Chang, S. Y., Peter, T., Thior, I., Foley, B. T., Gaolekwe, S., Rybak, N., Gaseitsiwe, S., Vannberg, F., Marlink, R., Lee, T. H., Essex, M. (2002). Human Immunodeficiency Virus Type 1 Subtype C Molecular Phylogeny: Consensus Sequence for an AIDS Vaccine Design?. J. Virol. 76: 5435-5451 [Abstract] [Full Text]  
  • Casimiro, D. R., Tang, A., Perry, H. C., Long, R. S., Chen, M., Heidecker, G. J., Davies, M.-E., Freed, D. C., Persaud, N. V., Dubey, S., Smith, J. G., Havlir, D., Richman, D., Chastain, M. A., Simon, A. J., Fu, T.-M., Emini, E. A., Shiver, J. W. (2002). Vaccine-Induced Immune Responses in Rodents and Nonhuman Primates by Use of a Humanized Human Immunodeficiency Virus Type 1 pol Gene. J. Virol. 76: 185-194 [Abstract] [Full Text]  
  • Lifson, J. D., Rossio, J. L., Piatak, M. Jr., Parks, T., Li, L., Kiser, R., Coalter, V., Fisher, B., Flynn, B. M., Czajak, S., Hirsch, V. M., Reimann, K. A., Schmitz, J. E., Ghrayeb, J., Bischofberger, N., Nowak, M. A., Desrosiers, R. C., Wodarz, D. (2001). Role of CD8+ Lymphocytes in Control of Simian Immunodeficiency Virus Infection and Resistance to Rechallenge after Transient Early Antiretroviral Treatment. J. Virol. 75: 10187-10199 [Abstract] [Full Text]  
  • Giannecchini, S., Matteucci, D., Ferrari, A., Pistello, M., Bendinelli, M. (2001). Feline Immunodeficiency Virus-Infected Cat Sera Associated with the Development of Broad Neutralization Resistance In Vivo Drive Similar Reversions In Vitro. J. Virol. 75: 8868-8873 [Abstract] [Full Text]  
  • Hofmann-Lehmann, R., Vlasak, J., Rasmussen, R. A., Smith, B. A., Baba, T. W., Liska, V., Ferrantelli, F., Montefiori, D. C., McClure, H. M., Anderson, D. C., Bernacky, B. J., Rizvi, T. A., Schmidt, R., Hill, L. R., Keeling, M. E., Katinger, H., Stiegler, G., Cavacini, L. A., Posner, M. R., Chou, T.-C., Andersen, J., Ruprecht, R. M. (2001). Postnatal Passive Immunization of Neonatal Macaques with a Triple Combination of Human Monoclonal Antibodies against Oral Simian-Human Immunodeficiency Virus Challenge. J. Virol. 75: 7470-7480 [Abstract] [Full Text]  
  • Barouch, D. H., Santra, S., Kuroda, M. J., Schmitz, J. E., Plishka, R., Buckler-White, A., Gaitan, A. E., Zin, R., Nam, J.-H., Wyatt, L. S., Lifton, M. A., Nickerson, C. E., Moss, B., Montefiori, D. C., Hirsch, V. M., Letvin, N. L. (2001). Reduction of Simian-Human Immunodeficiency Virus 89.6P Viremia in Rhesus Monkeys by Recombinant Modified Vaccinia Virus Ankara Vaccination. J. Virol. 75: 5151-5158 [Abstract] [Full Text]  
  • Guan, Y., Whitney, J. B., Detorio, M., Wainberg, M. A. (2001). Construction and In Vitro Properties of a Series of Attenuated Simian Immunodeficiency Viruses with All Accessory Genes Deleted. J. Virol. 75: 4056-4067 [Abstract] [Full Text]  
  • Guan, Y., Whitney, J. B., Liang, C., Wainberg, M. A. (2001). Novel, Live Attenuated Simian Immunodeficiency Virus Constructs Containing Major Deletions in Leader RNA Sequences. J. Virol. 75: 2776-2785 [Abstract] [Full Text]  
  • Khatissian, E., Monceaux, V., Cumont, M.-C., Kieny, M.-P., Aubertin, A.-M., Hurtrel, B. (2001). Persistence of Pathogenic Challenge Virus in Macaques Protected by Simian Immunodeficiency Virus SIVmac{Delta}nef. J. Virol. 75: 1507-1515 [Abstract] [Full Text]  
  • Fultz, P. N., Vance, P. J., Endres, M. J., Tao, B., Dvorin, J. D., Davis, I. C., Lifson, J. D., Montefiori, D. C., Marsh, M., Malim, M. H., Hoxie, J. A. (2001). In Vivo Attenuation of Simian Immunodeficiency Virus by Disruption of a Tyrosine-Dependent Sorting Signal in the Envelope Glycoprotein Cytoplasmic Tail. J. Virol. 75: 278-291 [Abstract] [Full Text]  
  • Silverstein, P. S., Mackay, G. A., Mukherjee, S., Li, Z., Piatak, M. Jr., Lifson, J. D., Narayan, O., Kumar, A. (2000). Pathogenic Simian/Human Immunodeficiency Virus SHIVKU Inoculated into Immunized Macaques Caused Infection, but Virus Burdens Progressively Declined with Time. J. Virol. 74: 10489-10497 [Abstract] [Full Text]  
  • Barouch, D. H., Santra, S., Schmitz, J. E., Kuroda, M. J., Fu, T.-M., Wagner, W., Bilska, M., Craiu, A., Zheng, X. X., Krivulka, G. R., Beaudry, K., Lifton, M. A., Nickerson, C. E., Trigona, W. L., Punt, K., Freed, D. C., Guan, L., Dubey, S., Casimiro, D., Simon, A., Davies, M.-E., Chastain, M., Strom, T. B., Gelman, R. S., Montefiori, D. C., Lewis, M. G., Emini, E. A., Shiver, J. W., Letvin, N. L. (2000). Control of Viremia and Prevention of Clinical AIDS in Rhesus Monkeys by Cytokine-Augmented DNA Vaccination. Science 290: 486-492 [Abstract] [Full Text]  
  • Hosie, M. J., Dunsford, T., Klein, D., Willett, B. J., Cannon, C., Osborne, R., MacDonald, J., Spibey, N., Mackay, N., Jarrett, O., Neil, J. C. (2000). Vaccination with Inactivated Virus but Not Viral DNA Reduces Virus Load following Challenge with a Heterologous and Virulent Isolate of Feline Immunodeficiency Virus. J. Virol. 74: 9403-9411 [Abstract] [Full Text]  
  • Dejucq, N. (2000). HIV-1 replication in CD4+ T cell lines: the effects of adaptation on co-receptor use, tropism, and accessory gene function. J. Leukoc. Biol. 68: 331-337 [Abstract] [Full Text]  
  • Murphy, C. G., Lucas, W. T., Means, R. E., Czajak, S., Hale, C. L., Lifson, J. D., Kaur, A., Johnson, R. P., Knipe, D. M., Desrosiers, R. C. (2000). Vaccine Protection against Simian Immunodeficiency Virus by Recombinant Strains of Herpes Simplex Virus. J. Virol. 74: 7745-7754 [Abstract] [Full Text]  
  • Metzner, K. J., Jin, X., Lee, F. V., Gettie, A., Bauer, D. E., Di Mascio, M., Perelson, A. S., Marx, P. A., Ho, D. D., Kostrikis, L. G., Connor, R. I. (2000). Effects of in Vivo Cd8+ T Cell Depletion on Virus Replication in Rhesus Macaques Immunized with a Live, Attenuated Simian Immunodeficiency Virus Vaccine. JEM 191: 1921-1932 [Abstract] [Full Text]  
  • Gundlach, B. R., Lewis, M. G., Sopper, S., Schnell, T., Sodroski, J., Stahl-Hennig, C., Überla, K. (2000). Evidence for Recombination of Live, Attenuated Immunodeficiency Virus Vaccine with Challenge Virus to a More Virulent Strain. J. Virol. 74: 3537-3542 [Abstract] [Full Text]  
  • Marzio, G., Verhoef, K., Vink, M., Berkhout, B. (2001). In vitro evolution of a highly replicating, doxycycline-dependent HIV for applications in vaccine studies. Proc. Natl. Acad. Sci. USA 98: 6342-6347 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»